Evaluation of Tumor-Targeting Properties of an Antagonistic Bombesin Analogue RM26 Conjugated with a Non-Residualizing Radioiodine Label Comparison with a Radiometal-Labelled Counterpart
Identifieur interne : 000883 ( Ncbi/Merge ); précédent : 000882; suivant : 000884Evaluation of Tumor-Targeting Properties of an Antagonistic Bombesin Analogue RM26 Conjugated with a Non-Residualizing Radioiodine Label Comparison with a Radiometal-Labelled Counterpart
Auteurs : Maryam Oroujeni [Suède] ; Ayman Abouzayed [Suède] ; Fanny Lundmark [Suède] ; Bogdan Mitran [Suède] ; Anna Orlova [Suède] ; Vladimir Tolmachev [Suède] ; Ulrika Rosenström [Suède]Source :
- Pharmaceutics [ 1999-4923 ] ; 2019.
Abstract
Radiolabelled antagonistic bombesin analogues are successfully used for targeting of gastrin-releasing peptide receptors (GRPR) that are overexpressed in prostate cancer. Internalization of antagonistic bombesin analogues is slow. We hypothesized that the use of a non-residualizing radioiodine label might not affect the tumour uptake but would reduce the retention in normal organs, where radiopharmaceutical would be internalized. To test this hypothesis, tyrosine was conjugated via diethylene glycol linker to N-terminus of an antagonistic bombesin analogue RM26 to form Tyr-PEG2-RM26. [111In]In-DOTA-PEG2-RM26 was used as a control with a residualizing label. Tyr-PEG2-RM26 was labelled with 125I with 95% radiochemical purity and retained binding specificity to GRPR. The IC50 values for Tyr-PEG2-RM26 and DOTA-PEG2-RM26 were 1.7 ± 0.3 nM and 3.3 ± 0.5 nM, respectively. The cellular processing of [125I]I-Tyr-PEG2-RM26 by PC-3 cells showed unusually fast internalization. Biodistribution showed that uptake in pancreas and tumour was GRPR-specific for both radioconjugates. Blood clearance of [125I]I-Tyr-PEG2-RM26 was appreciably slower and activity accumulation in all organs was significantly higher than for [111In]In-DOTA-PEG2-RM26. Tumor uptake of [111In]In-DOTA-PEG2-RM26 was significantly higher than for [125I]I-Tyr-PEG2-RM26, resulting in higher tumour-to-organ ratio for [111In]In-DOTA-PEG2-RM26 at studied time points. Incorporation of amino acids with hydrophilic side-chains next to tyrosine might overcome the problems associated with the use of tyrosine as a prosthetic group for radioiodination.
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DOI: 10.3390/pharmaceutics11080380
PubMed: 31382362
PubMed Central: 6724035
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xml:lang="fr">Suède</country><wicri:regionArea>Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="Abouzayed, Ayman" sort="Abouzayed, Ayman" uniqKey="Abouzayed A" first="Ayman" last="Abouzayed">Ayman Abouzayed</name><affiliation wicri:level="4"><nlm:aff id="af2-pharmaceutics-11-00380">Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="Lundmark, Fanny" sort="Lundmark, Fanny" uniqKey="Lundmark F" first="Fanny" last="Lundmark">Fanny Lundmark</name><affiliation wicri:level="4"><nlm:aff id="af2-pharmaceutics-11-00380">Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="Mitran, Bogdan" sort="Mitran, Bogdan" uniqKey="Mitran B" first="Bogdan" last="Mitran">Bogdan Mitran</name><affiliation wicri:level="4"><nlm:aff id="af2-pharmaceutics-11-00380">Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="Orlova, Anna" sort="Orlova, Anna" uniqKey="Orlova A" first="Anna" last="Orlova">Anna Orlova</name><affiliation wicri:level="4"><nlm:aff id="af2-pharmaceutics-11-00380">Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="af3-pharmaceutics-11-00380">Science for Life Laboratory, Uppsala University, SE-750 03 Uppsala, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Science for Life Laboratory, Uppsala University, SE-750 03 Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="Tolmachev, Vladimir" sort="Tolmachev, Vladimir" uniqKey="Tolmachev V" first="Vladimir" last="Tolmachev">Vladimir Tolmachev</name><affiliation wicri:level="4"><nlm:aff id="af1-pharmaceutics-11-00380">Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="Rosenstrom, Ulrika" sort="Rosenstrom, Ulrika" uniqKey="Rosenstrom U" first="Ulrika" last="Rosenström">Ulrika Rosenström</name><affiliation wicri:level="4"><nlm:aff id="af2-pharmaceutics-11-00380">Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author></analytic><series><title level="j">Pharmaceutics</title><idno type="eISSN">1999-4923</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Radiolabelled antagonistic bombesin analogues are successfully used for targeting of gastrin-releasing peptide receptors (GRPR) that are overexpressed in prostate cancer. Internalization of antagonistic bombesin analogues is slow. We hypothesized that the use of a non-residualizing radioiodine label might not affect the tumour uptake but would reduce the retention in normal organs, where radiopharmaceutical would be internalized. To test this hypothesis, tyrosine was conjugated via diethylene glycol linker to N-terminus of an antagonistic bombesin analogue RM26 to form Tyr-PEG<sub>2</sub>-RM26. [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 was used as a control with a residualizing label. Tyr-PEG<sub>2</sub>-RM26 was labelled with <sup>125</sup>I with 95% radiochemical purity and retained binding specificity to GRPR. The IC<sub>50</sub> values for Tyr-PEG<sub>2</sub>-RM26 and DOTA-PEG<sub>2</sub>-RM26 were 1.7 ± 0.3 nM and 3.3 ± 0.5 nM, respectively. The cellular processing of [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 by PC-3 cells showed unusually fast internalization. Biodistribution showed that uptake in pancreas and tumour was GRPR-specific for both radioconjugates. Blood clearance of [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 was appreciably slower and activity accumulation in all organs was significantly higher than for [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26. Tumor uptake of [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 was significantly higher than for [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26, resulting in higher tumour-to-organ ratio for [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 at studied time points. Incorporation of amino acids with hydrophilic side-chains next to tyrosine might overcome the problems associated with the use of tyrosine as a prosthetic group for radioiodination.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Siegel, R L" uniqKey="Siegel R">R.L. Siegel</name></author><author><name sortKey="Miller, K D" uniqKey="Miller K">K.D. Miller</name></author><author><name sortKey="Jemal, A" uniqKey="Jemal A">A. Jemal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aragon Ching, J B" uniqKey="Aragon Ching J">J.B. Aragon-Ching</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yuan, X" uniqKey="Yuan X">X. Yuan</name></author><author><name sortKey="Cai, C" uniqKey="Cai C">C. Cai</name></author><author><name sortKey="Chen, S" uniqKey="Chen S">S. Chen</name></author><author><name sortKey="Yu, Z" uniqKey="Yu Z">Z. Yu</name></author><author><name sortKey="Balk, S P" uniqKey="Balk S">S.P. Balk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Emmett, L" uniqKey="Emmett L">L. Emmett</name></author><author><name sortKey="Willowson, K" uniqKey="Willowson K">K. Willowson</name></author><author><name sortKey="Violet, J" uniqKey="Violet J">J. Violet</name></author><author><name sortKey="Shin, J" uniqKey="Shin J">J. Shin</name></author><author><name sortKey="Blanksby, A" uniqKey="Blanksby A">A. Blanksby</name></author><author><name sortKey="Lee, J" uniqKey="Lee J">J. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kratochwil, C" uniqKey="Kratochwil C">C. Kratochwil</name></author><author><name sortKey="Bruchertseifer, F" uniqKey="Bruchertseifer F">F. Bruchertseifer</name></author><author><name sortKey="Rathke, H" uniqKey="Rathke H">H. Rathke</name></author><author><name sortKey="Hohenfellner, M" uniqKey="Hohenfellner M">M. Hohenfellner</name></author><author><name sortKey="Giesel, F L" uniqKey="Giesel F">F.L. Giesel</name></author><author><name sortKey="Haberkorn, U" uniqKey="Haberkorn U">U. Haberkorn</name></author><author><name sortKey="Morgenstern, A" uniqKey="Morgenstern A">A. Morgenstern</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Silver, D A" uniqKey="Silver D">D.A. Silver</name></author><author><name sortKey="Pellicer, I" uniqKey="Pellicer I">I. Pellicer</name></author><author><name sortKey="Fair, W R" uniqKey="Fair W">W.R. Fair</name></author><author><name sortKey="Heston, W D" uniqKey="Heston W">W.D. Heston</name></author><author><name sortKey="Cordon Cardo, C" uniqKey="Cordon Cardo C">C. Cordon-Cardo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spatz, S" uniqKey="Spatz S">S. Spatz</name></author><author><name sortKey="Tolkach, Y" uniqKey="Tolkach Y">Y. Tolkach</name></author><author><name sortKey="Jung, K" uniqKey="Jung K">K. Jung</name></author><author><name sortKey="Stephan, C" uniqKey="Stephan C">C. Stephan</name></author><author><name sortKey="Busch, J" uniqKey="Busch J">J. Busch</name></author><author><name sortKey="Ralla, B" uniqKey="Ralla B">B. Ralla</name></author><author><name sortKey="Rabien, A" uniqKey="Rabien A">A. Rabien</name></author><author><name sortKey="Feldmann, G" uniqKey="Feldmann G">G. Feldmann</name></author><author><name sortKey="Brossart, P" uniqKey="Brossart P">P. Brossart</name></author><author><name sortKey="Bundschuh, R A" uniqKey="Bundschuh R">R.A. Bundschuh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheikhbahaei, S" uniqKey="Sheikhbahaei S">S. Sheikhbahaei</name></author><author><name sortKey="Afshar Oromieh, A" uniqKey="Afshar Oromieh A">A. Afshar-Oromieh</name></author><author><name sortKey="Eiber, M" uniqKey="Eiber M">M. Eiber</name></author><author><name sortKey="Solnes, L B" uniqKey="Solnes L">L.B. Solnes</name></author><author><name sortKey="Javadi, M S" uniqKey="Javadi M">M.S. Javadi</name></author><author><name sortKey="Ross, A E" uniqKey="Ross A">A.E. Ross</name></author><author><name sortKey="Pienta, K J" uniqKey="Pienta K">K.J. Pienta</name></author><author><name sortKey="Allaf, M E" uniqKey="Allaf M">M.E. Allaf</name></author><author><name sortKey="Haberkorn, U" uniqKey="Haberkorn U">U. Haberkorn</name></author><author><name sortKey="Pomper, M G" uniqKey="Pomper M">M.G. Pomper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ananias, H J" uniqKey="Ananias H">H.J. Ananias</name></author><author><name sortKey="Van Den Heuvel, M C" uniqKey="Van Den Heuvel M">M.C. van den Heuvel</name></author><author><name sortKey="Helfrich, W" uniqKey="Helfrich W">W. Helfrich</name></author><author><name sortKey="De Jong, I J" uniqKey="De Jong I">I.J. de Jong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reubi, J C" uniqKey="Reubi J">J.C. Reubi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van De Wiele, C" uniqKey="Van De Wiele C">C. Van de Wiele</name></author><author><name sortKey="Dumont, F" uniqKey="Dumont F">F. Dumont</name></author><author><name sortKey="Vanden Broecke, R" uniqKey="Vanden Broecke R">R. Vanden Broecke</name></author><author><name sortKey="Oosterlinck, W" uniqKey="Oosterlinck W">W. Oosterlinck</name></author><author><name sortKey="Cocquyt, V" uniqKey="Cocquyt V">V. Cocquyt</name></author><author><name sortKey="Serreyn, R" uniqKey="Serreyn R">R. Serreyn</name></author><author><name sortKey="Peers, S" uniqKey="Peers S">S. Peers</name></author><author><name sortKey="Thornback, J" uniqKey="Thornback J">J. Thornback</name></author><author><name sortKey="Slegers, G" uniqKey="Slegers G">G. Slegers</name></author><author><name sortKey="Dierckx, R A" uniqKey="Dierckx R">R.A. Dierckx</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jensen, R T" uniqKey="Jensen R">R.T. Jensen</name></author><author><name sortKey="Battey, J F" uniqKey="Battey J">J.F. Battey</name></author><author><name sortKey="Spindel, E R" uniqKey="Spindel E">E.R. Spindel</name></author><author><name sortKey="Benya, R V" uniqKey="Benya R">R.V. Benya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nock, B A" uniqKey="Nock B">B.A. Nock</name></author><author><name sortKey="Nikolopoulou, A" uniqKey="Nikolopoulou A">A. Nikolopoulou</name></author><author><name sortKey="Galanis, A" uniqKey="Galanis A">A. Galanis</name></author><author><name sortKey="Cordopatis, P" uniqKey="Cordopatis P">P. Cordopatis</name></author><author><name sortKey="Waser, B" uniqKey="Waser B">B. Waser</name></author><author><name sortKey="Reubi, J C" uniqKey="Reubi J">J.C. Reubi</name></author><author><name sortKey="Maina, T" uniqKey="Maina T">T. Maina</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, X" uniqKey="Zhang X">X. Zhang</name></author><author><name sortKey="Cai, W" uniqKey="Cai W">W. Cai</name></author><author><name sortKey="Cao, F" uniqKey="Cao F">F. Cao</name></author><author><name sortKey="Schreibmann, E" uniqKey="Schreibmann E">E. Schreibmann</name></author><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y. Wu</name></author><author><name sortKey="Wu, J C" uniqKey="Wu J">J.C. Wu</name></author><author><name sortKey="Xing, L" uniqKey="Xing L">L. Xing</name></author><author><name sortKey="Chen, X" uniqKey="Chen X">X. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dimitrakopoulou Strauss, A" uniqKey="Dimitrakopoulou Strauss A">A. Dimitrakopoulou-Strauss</name></author><author><name sortKey="Hohenberger, P" uniqKey="Hohenberger P">P. Hohenberger</name></author><author><name sortKey="Haberkorn, U" uniqKey="Haberkorn U">U. Haberkorn</name></author><author><name sortKey="Macke, H R" uniqKey="Macke H">H.R. Macke</name></author><author><name sortKey="Eisenhut, M" uniqKey="Eisenhut M">M. Eisenhut</name></author><author><name sortKey="Strauss, L G" uniqKey="Strauss L">L.G. Strauss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="D Pp, S" uniqKey="D Pp S">S. Däpp</name></author><author><name sortKey="Muller, C" uniqKey="Muller C">C. Müller</name></author><author><name sortKey="Garayoa, E G" uniqKey="Garayoa E">E.G. Garayoa</name></author><author><name sortKey="Bl Uenstein, P" uniqKey="Bl Uenstein P">P. Bläuenstein</name></author><author><name sortKey="Maes, V" uniqKey="Maes V">V. Maes</name></author><author><name sortKey="Brans, L" uniqKey="Brans L">L. Brans</name></author><author><name sortKey="Tourwe, D A" uniqKey="Tourwe D">D.A. Tourwé</name></author><author><name sortKey="Schibli, R" uniqKey="Schibli R">R. Schibli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wild, D" uniqKey="Wild D">D. Wild</name></author><author><name sortKey="Frischknecht, M" uniqKey="Frischknecht M">M. Frischknecht</name></author><author><name sortKey="Zhang, H" uniqKey="Zhang H">H. Zhang</name></author><author><name sortKey="Morgenstern, A" uniqKey="Morgenstern A">A. Morgenstern</name></author><author><name sortKey="Bruchertseifer, F" uniqKey="Bruchertseifer F">F. Bruchertseifer</name></author><author><name sortKey="Boisclair, J" uniqKey="Boisclair J">J. Boisclair</name></author><author><name sortKey="Provencher Bolliger, A" uniqKey="Provencher Bolliger A">A. Provencher-Bolliger</name></author><author><name sortKey="Reubi, J C" uniqKey="Reubi J">J.C. Reubi</name></author><author><name sortKey="Maecke, H R" uniqKey="Maecke H">H.R. Maecke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, C J" uniqKey="Smith C">C.J. Smith</name></author><author><name sortKey="Sieckman, G L" uniqKey="Sieckman G">G.L. Sieckman</name></author><author><name sortKey="Owen, N K" uniqKey="Owen N">N.K. Owen</name></author><author><name sortKey="Hayes, D L" uniqKey="Hayes D">D.L. Hayes</name></author><author><name sortKey="Mazuru, D G" uniqKey="Mazuru D">D.G. Mazuru</name></author><author><name sortKey="Volkert, W A" uniqKey="Volkert W">W.A. Volkert</name></author><author><name sortKey="Hoffman, T J" uniqKey="Hoffman T">T.J. Hoffman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lantry, L E" uniqKey="Lantry L">L.E. Lantry</name></author><author><name sortKey="Cappelletti, E" uniqKey="Cappelletti E">E. Cappelletti</name></author><author><name sortKey="Maddalena, M E" uniqKey="Maddalena M">M.E. Maddalena</name></author><author><name sortKey="Fox, J S" uniqKey="Fox J">J.S. Fox</name></author><author><name sortKey="Feng, W" uniqKey="Feng W">W. Feng</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J. Chen</name></author><author><name sortKey="Thomas, R" uniqKey="Thomas R">R. Thomas</name></author><author><name sortKey="Eaton, S M" uniqKey="Eaton S">S.M. Eaton</name></author><author><name sortKey="Bogdan, N J" uniqKey="Bogdan N">N.J. Bogdan</name></author><author><name sortKey="Arunachalam, T" uniqKey="Arunachalam T">T. Arunachalam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Koumarianou, E" uniqKey="Koumarianou E">E. Koumarianou</name></author><author><name sortKey="Mikolajczak, R" uniqKey="Mikolajczak R">R. Mikołajczak</name></author><author><name sortKey="Pawlak, D" uniqKey="Pawlak D">D. Pawlak</name></author><author><name sortKey="Zikos, X" uniqKey="Zikos X">X. Zikos</name></author><author><name sortKey="Bouziotis, P" uniqKey="Bouziotis P">P. Bouziotis</name></author><author><name sortKey="Garnuszek, P" uniqKey="Garnuszek P">P. Garnuszek</name></author><author><name sortKey="Karczmarczyk, U" uniqKey="Karczmarczyk U">U. Karczmarczyk</name></author><author><name sortKey="Maurin, M" uniqKey="Maurin M">M. Maurin</name></author><author><name sortKey="Archimandritis, S C" uniqKey="Archimandritis S">S.C. Archimandritis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nock, B" uniqKey="Nock B">B. Nock</name></author><author><name sortKey="Nikolopoulou, A" uniqKey="Nikolopoulou A">A. Nikolopoulou</name></author><author><name sortKey="Chiotellis, E" uniqKey="Chiotellis E">E. Chiotellis</name></author><author><name sortKey="Loudos, G" uniqKey="Loudos G">G. Loudos</name></author><author><name sortKey="Maintas, D" uniqKey="Maintas D">D. Maintas</name></author><author><name sortKey="Reubi, J C" uniqKey="Reubi J">J.C. Reubi</name></author><author><name sortKey="Maina, T" uniqKey="Maina T">T. Maina</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abiraj, K" uniqKey="Abiraj K">K. Abiraj</name></author><author><name sortKey="Mansi, R" uniqKey="Mansi R">R. Mansi</name></author><author><name sortKey="Tamma, M L" uniqKey="Tamma M">M.L. Tamma</name></author><author><name sortKey="Fani, M" uniqKey="Fani M">M. Fani</name></author><author><name sortKey="Forrer, F" uniqKey="Forrer F">F. Forrer</name></author><author><name sortKey="Nicolas, G" uniqKey="Nicolas G">G. Nicolas</name></author><author><name sortKey="Cescato, R" uniqKey="Cescato R">R. Cescato</name></author><author><name sortKey="Reubi, J C" uniqKey="Reubi J">J.C. Reubi</name></author><author><name sortKey="Maecke, H R" uniqKey="Maecke H">H.R. Maecke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cescato, R" uniqKey="Cescato R">R. Cescato</name></author><author><name sortKey="Maina, T" uniqKey="Maina T">T. Maina</name></author><author><name sortKey="Nock, B" uniqKey="Nock B">B. Nock</name></author><author><name sortKey="Nikolopoulou, A" uniqKey="Nikolopoulou A">A. Nikolopoulou</name></author><author><name sortKey="Charalambidis, D" uniqKey="Charalambidis D">D. Charalambidis</name></author><author><name sortKey="Piccand, V" uniqKey="Piccand V">V. Piccand</name></author><author><name sortKey="Reubi, J C" uniqKey="Reubi J">J.C. Reubi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mansi, R" uniqKey="Mansi R">R. Mansi</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X. Wang</name></author><author><name sortKey="Forrer, F" uniqKey="Forrer F">F. Forrer</name></author><author><name sortKey="Kneifel, S" uniqKey="Kneifel S">S. Kneifel</name></author><author><name sortKey="Tamma, M L" uniqKey="Tamma M">M.L. Tamma</name></author><author><name sortKey="Waser, B" uniqKey="Waser B">B. Waser</name></author><author><name sortKey="Cescato, R" uniqKey="Cescato R">R. Cescato</name></author><author><name sortKey="Reubi, J C" uniqKey="Reubi J">J.C. Reubi</name></author><author><name sortKey="Maecke, H R" uniqKey="Maecke H">H.R. Maecke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dumont, R A" uniqKey="Dumont R">R.A. Dumont</name></author><author><name sortKey="Tamma, M" uniqKey="Tamma M">M. Tamma</name></author><author><name sortKey="Braun, F" uniqKey="Braun F">F. Braun</name></author><author><name sortKey="Borkowski, S" uniqKey="Borkowski S">S. Borkowski</name></author><author><name sortKey="Reubi, J C" uniqKey="Reubi J">J.C. Reubi</name></author><author><name sortKey="Maecke, H" uniqKey="Maecke H">H. Maecke</name></author><author><name sortKey="Weber, W A" uniqKey="Weber W">W.A. Weber</name></author><author><name sortKey="Mansi, R" uniqKey="Mansi R">R. Mansi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chatalic, K L" uniqKey="Chatalic K">K.L. Chatalic</name></author><author><name sortKey="Konijnenberg, M" uniqKey="Konijnenberg M">M. Konijnenberg</name></author><author><name sortKey="Nonnekens, J" uniqKey="Nonnekens J">J. Nonnekens</name></author><author><name sortKey="De Blois, E" uniqKey="De Blois E">E. de Blois</name></author><author><name sortKey="Hoeben, S" uniqKey="Hoeben S">S. Hoeben</name></author><author><name sortKey="De Ridder, C" uniqKey="De Ridder C">C. de Ridder</name></author><author><name sortKey="Brunel, L" uniqKey="Brunel L">L. Brunel</name></author><author><name sortKey="Fehrentz, J A" uniqKey="Fehrentz J">J.A. Fehrentz</name></author><author><name sortKey="Martinez, J" uniqKey="Martinez J">J. Martinez</name></author><author><name sortKey="Van Gent, D C" uniqKey="Van Gent D">D.C. van Gent</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nock, B A" uniqKey="Nock B">B.A. Nock</name></author><author><name sortKey="Kaloudi, A" uniqKey="Kaloudi A">A. Kaloudi</name></author><author><name sortKey="Lymperis, E" uniqKey="Lymperis E">E. Lymperis</name></author><author><name sortKey="Giarika, A" uniqKey="Giarika A">A. Giarika</name></author><author><name sortKey="Kulkarni, H R" uniqKey="Kulkarni H">H.R. Kulkarni</name></author><author><name sortKey="Klette, I" uniqKey="Klette I">I. Klette</name></author><author><name sortKey="Singh, A" uniqKey="Singh A">A. Singh</name></author><author><name sortKey="Krenning, E P" uniqKey="Krenning E">E.P. Krenning</name></author><author><name sortKey="De Jong, M" uniqKey="De Jong M">M. de Jong</name></author><author><name sortKey="Maina, T" uniqKey="Maina T">T. Maina</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tolmachev, V" uniqKey="Tolmachev V">V. Tolmachev</name></author><author><name sortKey="Mume, E" uniqKey="Mume E">E. Mume</name></author><author><name sortKey="Sjoberg, S" uniqKey="Sjoberg S">S. Sjöberg</name></author><author><name sortKey="Frejd, F Y" uniqKey="Frejd F">F.Y. Frejd</name></author><author><name sortKey="Orlova, A" uniqKey="Orlova A">A. Orlova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lindbo, S" uniqKey="Lindbo S">S. Lindbo</name></author><author><name sortKey="Garousi, J" uniqKey="Garousi J">J. Garousi</name></author><author><name sortKey="Mitran, B" uniqKey="Mitran B">B. Mitran</name></author><author><name sortKey="Altai, M" uniqKey="Altai M">M. Altai</name></author><author><name sortKey="Buijs, J" uniqKey="Buijs J">J. Buijs</name></author><author><name sortKey="Orlova, A" uniqKey="Orlova A">A. Orlova</name></author><author><name sortKey="Hober, S" uniqKey="Hober S">S. Hober</name></author><author><name sortKey="Tolmachev, V" uniqKey="Tolmachev V">V. Tolmachev</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wilbur, S" uniqKey="Wilbur S">S. Wilbur</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Llinares, M" uniqKey="Llinares M">M. Llinares</name></author><author><name sortKey="Devin, C" uniqKey="Devin C">C. Devin</name></author><author><name sortKey="Chaloin, O" uniqKey="Chaloin O">O. Chaloin</name></author><author><name sortKey="Azay, J" uniqKey="Azay J">J. Azay</name></author><author><name sortKey="Noel Artis, A M" uniqKey="Noel Artis A">A.M. Noel-Artis</name></author><author><name sortKey="Bernad, N" uniqKey="Bernad N">N. Bernad</name></author><author><name sortKey="Fehrentz, J A" uniqKey="Fehrentz J">J.A. Fehrentz</name></author><author><name sortKey="Martinez, J" uniqKey="Martinez J">J. Martinez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Varasteh, Z" uniqKey="Varasteh Z">Z. Varasteh</name></author><author><name sortKey="Velikyan, I" uniqKey="Velikyan I">I. Velikyan</name></author><author><name sortKey="Lindeberg, G" uniqKey="Lindeberg G">G. Lindeberg</name></author><author><name sortKey="Sorensen, J" uniqKey="Sorensen J">J. Sörensen</name></author><author><name sortKey="Larhed, M" uniqKey="Larhed M">M. Larhed</name></author><author><name sortKey="Sandstrom, M" uniqKey="Sandstrom M">M. Sandström</name></author><author><name sortKey="Selvaraju, R K" uniqKey="Selvaraju R">R.K. Selvaraju</name></author><author><name sortKey="Malmberg, J" uniqKey="Malmberg J">J. Malmberg</name></author><author><name sortKey="Tolmachev, V" uniqKey="Tolmachev V">V. Tolmachev</name></author><author><name sortKey="Orlova, A" uniqKey="Orlova A">A. Orlova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Varasteh, Z" uniqKey="Varasteh Z">Z. Varasteh</name></author><author><name sortKey="Rosenstrom, U" uniqKey="Rosenstrom U">U. Rosenström</name></author><author><name sortKey="Velikyan, I" uniqKey="Velikyan I">I. Velikyan</name></author><author><name sortKey="Mitran, B" uniqKey="Mitran B">B. Mitran</name></author><author><name sortKey="Altai, M" uniqKey="Altai M">M. Altai</name></author><author><name sortKey="Honarvar, H" uniqKey="Honarvar H">H. Honarvar</name></author><author><name sortKey="Rosestedt, M" uniqKey="Rosestedt M">M. Rosestedt</name></author><author><name sortKey="Lindeberg, G" uniqKey="Lindeberg G">G. Lindeberg</name></author><author><name sortKey="Sorensen, J" uniqKey="Sorensen J">J. Sörensen</name></author><author><name sortKey="Larhed, M" uniqKey="Larhed M">M. Larhed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Varasteh, Z" uniqKey="Varasteh Z">Z. Varasteh</name></author><author><name sortKey="Mitran, B" uniqKey="Mitran B">B. Mitran</name></author><author><name sortKey="Rosenstrom, U" uniqKey="Rosenstrom U">U. Rosenström</name></author><author><name sortKey="Velikyan, I" uniqKey="Velikyan I">I. Velikyan</name></author><author><name sortKey="Rosestedt, M" uniqKey="Rosestedt M">M. Rosestedt</name></author><author><name sortKey="Lindeberg, G" uniqKey="Lindeberg G">G. Lindeberg</name></author><author><name sortKey="Sorensen, J" uniqKey="Sorensen J">J. Sörensen</name></author><author><name sortKey="Larhed, M" uniqKey="Larhed M">M. Larhed</name></author><author><name sortKey="Tolmachev, V" uniqKey="Tolmachev V">V. Tolmachev</name></author><author><name sortKey="Orlova, A" uniqKey="Orlova A">A. Orlova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Varasteh, Z" uniqKey="Varasteh Z">Z. Varasteh</name></author><author><name sortKey="Aberg, O" uniqKey="Aberg O">O. Aberg</name></author><author><name sortKey="Velikyan, I" uniqKey="Velikyan I">I. Velikyan</name></author><author><name sortKey="Lindeberg, G" uniqKey="Lindeberg G">G. Lindeberg</name></author><author><name sortKey="Sorensen, J" uniqKey="Sorensen J">J. Sörensen</name></author><author><name sortKey="Larhed, M" uniqKey="Larhed M">M. Larhed</name></author><author><name sortKey="Antoni, G" uniqKey="Antoni G">G. Antoni</name></author><author><name sortKey="Sandstrom, M" uniqKey="Sandstrom M">M. Sandström</name></author><author><name sortKey="Tolmachev, V" uniqKey="Tolmachev V">V. Tolmachev</name></author><author><name sortKey="Orlova, A" uniqKey="Orlova A">A. Orlova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mitran, B" uniqKey="Mitran B">B. Mitran</name></author><author><name sortKey="Thisgaard, H" uniqKey="Thisgaard H">H. Thisgaard</name></author><author><name sortKey="Rosenstrom, U" uniqKey="Rosenstrom U">U. Rosenström</name></author><author><name sortKey="Dam, J H" uniqKey="Dam J">J.H. Dam</name></author><author><name sortKey="Larhed, M" uniqKey="Larhed M">M. Larhed</name></author><author><name sortKey="Tolmachev, V" uniqKey="Tolmachev V">V. Tolmachev</name></author><author><name sortKey="Orlova, A" uniqKey="Orlova A">A. Orlova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mitran, B" uniqKey="Mitran B">B. Mitran</name></author><author><name sortKey="Rinne, S S" uniqKey="Rinne S">S.S. Rinne</name></author><author><name sortKey="Konijnenberg, M W" uniqKey="Konijnenberg M">M.W. Konijnenberg</name></author><author><name sortKey="Maina, T" uniqKey="Maina T">T. Maina</name></author><author><name sortKey="Nock, B A" uniqKey="Nock B">B.A. Nock</name></author><author><name sortKey="Altai, M" uniqKey="Altai M">M. Altai</name></author><author><name sortKey="Vorobyeva, A" uniqKey="Vorobyeva A">A. Vorobyeva</name></author><author><name sortKey="Larhed, M" uniqKey="Larhed M">M. Larhed</name></author><author><name sortKey="Tolmachev, V" uniqKey="Tolmachev V">V. Tolmachev</name></author><author><name sortKey="De Jong, M" uniqKey="De Jong M">M. de Jong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moody, T W" uniqKey="Moody T">T.W. Moody</name></author><author><name sortKey="Crawley, J N" uniqKey="Crawley J">J.N. Crawley</name></author><author><name sortKey="Jensen, R T" uniqKey="Jensen R">R.T. Jensen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Biddlecombe, G B" uniqKey="Biddlecombe G">G.B. Biddlecombe</name></author><author><name sortKey="Rogers, B E" uniqKey="Rogers B">B.E. Rogers</name></author><author><name sortKey="De Visser, M" uniqKey="De Visser M">M. de Visser</name></author><author><name sortKey="Parry, J J" uniqKey="Parry J">J.J. Parry</name></author><author><name sortKey="De Jong, M" uniqKey="De Jong M">M. de Jong</name></author><author><name sortKey="Erion, J L" uniqKey="Erion J">J.L. Erion</name></author><author><name sortKey="Lewis, J S" uniqKey="Lewis J">J.S. Lewis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoffman, T J" uniqKey="Hoffman T">T.J. Hoffman</name></author><author><name sortKey="Gali, H" uniqKey="Gali H">H. Gali</name></author><author><name sortKey="Smith, C J" uniqKey="Smith C">C.J. Smith</name></author><author><name sortKey="Sieckman, G L" uniqKey="Sieckman G">G.L. Sieckman</name></author><author><name sortKey="Hayes, D L" uniqKey="Hayes D">D.L. Hayes</name></author><author><name sortKey="Owen, N K" uniqKey="Owen N">N.K. Owen</name></author><author><name sortKey="Volkert, W A" uniqKey="Volkert W">W.A. Volkert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mitran, B" uniqKey="Mitran B">B. Mitran</name></author><author><name sortKey="Varasteh, Z" uniqKey="Varasteh Z">Z. Varasteh</name></author><author><name sortKey="Selvaraju, R K" uniqKey="Selvaraju R">R.K. Selvaraju</name></author><author><name sortKey="Lindeberg, G" uniqKey="Lindeberg G">G. Lindeberg</name></author><author><name sortKey="Sorensen, J" uniqKey="Sorensen J">J. Sörensen</name></author><author><name sortKey="Larhed, M" uniqKey="Larhed M">M. Larhed</name></author><author><name sortKey="Tolmachev, V" uniqKey="Tolmachev V">V. Tolmachev</name></author><author><name sortKey="Rosenstrom, U" uniqKey="Rosenstrom U">U. Rosenström</name></author><author><name sortKey="Orlova, A" uniqKey="Orlova A">A. Orlova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Laznicek, M" uniqKey="Laznicek M">M. Láznícek</name></author><author><name sortKey="Kv Tina, J" uniqKey="Kv Tina J">J. Kvĕtina</name></author><author><name sortKey="Mazak, J" uniqKey="Mazak J">J. Mazák</name></author><author><name sortKey="Krch, V" uniqKey="Krch V">V. Krch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="W Llberg, H" uniqKey="W Llberg H">H. Wållberg</name></author><author><name sortKey="Orlova, A" uniqKey="Orlova A">A. Orlova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maddalena, M E" uniqKey="Maddalena M">M.E. Maddalena</name></author><author><name sortKey="Fox, J" uniqKey="Fox J">J. Fox</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J. Chen</name></author><author><name sortKey="Feng, W" uniqKey="Feng W">W. Feng</name></author><author><name sortKey="Cagnolini, A" uniqKey="Cagnolini A">A. Cagnolini</name></author><author><name sortKey="Linder, K E" uniqKey="Linder K">K.E. Linder</name></author><author><name sortKey="Tweedle, M F" uniqKey="Tweedle M">M.F. Tweedle</name></author><author><name sortKey="Nunn, A D" uniqKey="Nunn A">A.D. Nunn</name></author><author><name sortKey="Lantry, L E" uniqKey="Lantry L">L.E. Lantry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grady, E F" uniqKey="Grady E">E.F. Grady</name></author><author><name sortKey="Slice, L W" uniqKey="Slice L">L.W. Slice</name></author><author><name sortKey="Brant, W O" uniqKey="Brant W">W.O. Brant</name></author><author><name sortKey="Walsh, J H" uniqKey="Walsh J">J.H. Walsh</name></author><author><name sortKey="Payan, D G" uniqKey="Payan D">D.G. Payan</name></author><author><name sortKey="Bunnett, N W" uniqKey="Bunnett N">N.W. Bunnett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="La Bella, R" uniqKey="La Bella R">R. La Bella</name></author><author><name sortKey="Garcia Garayoa, E" uniqKey="Garcia Garayoa E">E. Garcia-Garayoa</name></author><author><name sortKey="Bahler, M" uniqKey="Bahler M">M. Bahler</name></author><author><name sortKey="Bl Uenstein, P" uniqKey="Bl Uenstein P">P. Bläuenstein</name></author><author><name sortKey="Schibli, R" uniqKey="Schibli R">R. Schibli</name></author><author><name sortKey="Conrath, P" uniqKey="Conrath P">P. Conrath</name></author><author><name sortKey="Tourwe, D" uniqKey="Tourwe D">D. Tourwé</name></author><author><name sortKey="Schubiger, P A" uniqKey="Schubiger P">P.A. Schubiger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garcia Garayoa, E" uniqKey="Garcia Garayoa E">E. García Garayoa</name></author><author><name sortKey="Schweinsberg, C" uniqKey="Schweinsberg C">C. Schweinsberg</name></author><author><name sortKey="Maes, V" uniqKey="Maes V">V. Maes</name></author><author><name sortKey="Ruegg, D" uniqKey="Ruegg D">D. Rüegg</name></author><author><name sortKey="Blanc, A" uniqKey="Blanc A">A. Blanc</name></author><author><name sortKey="Bl Uenstein, P" uniqKey="Bl Uenstein P">P. Bläuenstein</name></author><author><name sortKey="Tourwe, D A" uniqKey="Tourwe D">D.A. Tourwé</name></author><author><name sortKey="Beck Sickinger, A G" uniqKey="Beck Sickinger A">A.G. Beck-Sickinger</name></author><author><name sortKey="Schubiger, P A" uniqKey="Schubiger P">P.A. Schubiger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, H" uniqKey="Zhang H">H. Zhang</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J. Chen</name></author><author><name sortKey="Waldherr, C" uniqKey="Waldherr C">C. Waldherr</name></author><author><name sortKey="Hinni, K" uniqKey="Hinni K">K. Hinni</name></author><author><name sortKey="Waser, B" uniqKey="Waser B">B. Waser</name></author><author><name sortKey="Reubi, J C" uniqKey="Reubi J">J.C. Reubi</name></author><author><name sortKey="Maecke, H R" uniqKey="Maecke H">H.R. Maecke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garcia Garayoa, E" uniqKey="Garcia Garayoa E">E. García Garayoa</name></author><author><name sortKey="Schweinsberg, C" uniqKey="Schweinsberg C">C. Schweinsberg</name></author><author><name sortKey="Maes, V" uniqKey="Maes V">V. Maes</name></author><author><name sortKey="Brans, L" uniqKey="Brans L">L. Brans</name></author><author><name sortKey="Bl Uenstein, P" uniqKey="Bl Uenstein P">P. Bläuenstein</name></author><author><name sortKey="Tourwe, D A" uniqKey="Tourwe D">D.A. Tourwe</name></author><author><name sortKey="Schibli, R" uniqKey="Schibli R">R. Schibli</name></author><author><name sortKey="Schubiger, P A" uniqKey="Schubiger P">P.A. Schubiger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sundberg, A L" uniqKey="Sundberg A">A.L. Sundberg</name></author><author><name sortKey="Steffen, A" uniqKey="Steffen A">A. Steffen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reubi, J C" uniqKey="Reubi J">J.C. Reubi</name></author><author><name sortKey="Erchegyi, J" uniqKey="Erchegyi J">J. Erchegyi</name></author><author><name sortKey="Cescato, R" uniqKey="Cescato R">R. Cescato</name></author><author><name sortKey="Waser, B" uniqKey="Waser B">B. Waser</name></author><author><name sortKey="Rivier, J E" uniqKey="Rivier J">J.E. Rivier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shipp, M A" uniqKey="Shipp M">M.A. Shipp</name></author><author><name sortKey="Tarr, G E" uniqKey="Tarr G">G.E. Tarr</name></author><author><name sortKey="Chen, C Y" uniqKey="Chen C">C.Y. Chen</name></author><author><name sortKey="Switzer, S N" uniqKey="Switzer S">S.N. Switzer</name></author><author><name sortKey="Hersh, L B" uniqKey="Hersh L">L.B. Hersh</name></author><author><name sortKey="Stein, H" uniqKey="Stein H">H. Stein</name></author><author><name sortKey="Sunday, M E" uniqKey="Sunday M">M.E. Sunday</name></author><author><name sortKey="Reinherz, E L" uniqKey="Reinherz E">E.L. Reinherz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roques, B P" uniqKey="Roques B">B.P. Roques</name></author><author><name sortKey="Noble, F" uniqKey="Noble F">F. Noble</name></author><author><name sortKey="Dauge, V" uniqKey="Dauge V">V. Dauge</name></author><author><name sortKey="Fournie Zaluski, M C" uniqKey="Fournie Zaluski M">M.C. Fournié-Zaluski</name></author><author><name sortKey="Beaumont, A" uniqKey="Beaumont A">A. Beaumont</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nock, B A" uniqKey="Nock B">B.A. Nock</name></author><author><name sortKey="Maina, T" uniqKey="Maina T">T. Maina</name></author><author><name sortKey="Krenning, E P" uniqKey="Krenning E">E.P. Krenning</name></author><author><name sortKey="De Jong, M" uniqKey="De Jong M">M. de Jong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wittendorf, R W" uniqKey="Wittendorf R">R.W. Wittendorf</name></author><author><name sortKey="Swagzdis, J E" uniqKey="Swagzdis J">J.E. Swagzdis</name></author><author><name sortKey="Gifford, R" uniqKey="Gifford R">R. Gifford</name></author><author><name sortKey="Mico, B A" uniqKey="Mico B">B.A. Mico</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Decristoforo, C" uniqKey="Decristoforo C">C. Decristoforo</name></author><author><name sortKey="Mather, S J" uniqKey="Mather S">S.J. Mather</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Engfeldt, T" uniqKey="Engfeldt T">T. Engfeldt</name></author><author><name sortKey="Tran, T" uniqKey="Tran T">T. Tran</name></author><author><name sortKey="Orlova, A" uniqKey="Orlova A">A. Orlova</name></author><author><name sortKey="Widstrom, C" uniqKey="Widstrom C">C. Widström</name></author><author><name sortKey="Feldwisch, J" uniqKey="Feldwisch J">J. Feldwisch</name></author><author><name sortKey="Abrahmsen, L" uniqKey="Abrahmsen L">L. Abrahmsen</name></author><author><name sortKey="Wennborg, A" uniqKey="Wennborg A">A. Wennborg</name></author><author><name sortKey="Karlstrom, A E" uniqKey="Karlstrom A">A.E. Karlström</name></author><author><name sortKey="Tolmachev, V" uniqKey="Tolmachev V">V. Tolmachev</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tran, T" uniqKey="Tran T">T. Tran</name></author><author><name sortKey="Engfeldt, T" uniqKey="Engfeldt T">T. Engfeldt</name></author><author><name sortKey="Orlova, A" uniqKey="Orlova A">A. Orlova</name></author><author><name sortKey="Sandstrom, M" uniqKey="Sandstrom M">M. Sandström</name></author><author><name sortKey="Feldwisch, J" uniqKey="Feldwisch J">J. Feldwisch</name></author><author><name sortKey="Abrahmsen, L" uniqKey="Abrahmsen L">L. Abrahmsén</name></author><author><name sortKey="Wennborg, A" uniqKey="Wennborg A">A. Wennborg</name></author><author><name sortKey="Tolmachev, V" uniqKey="Tolmachev V">V. Tolmachev</name></author><author><name sortKey="Karlstrom, A E" uniqKey="Karlstrom A">A.E. Karlström</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rusckowski, M" uniqKey="Rusckowski M">M. Rusckowski</name></author><author><name sortKey="Qu, T" uniqKey="Qu T">T. Qu</name></author><author><name sortKey="Gupta, S" uniqKey="Gupta S">S. Gupta</name></author><author><name sortKey="Ley, A" uniqKey="Ley A">A. Ley</name></author><author><name sortKey="Hnatowich, D J" uniqKey="Hnatowich D">D.J. Hnatowich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rosik, D" uniqKey="Rosik D">D. Rosik</name></author><author><name sortKey="Thibblin, A" uniqKey="Thibblin A">A. Thibblin</name></author><author><name sortKey="Antoni, G" uniqKey="Antoni G">G. Antoni</name></author><author><name sortKey="Honarvar, H" uniqKey="Honarvar H">H. Honarvar</name></author><author><name sortKey="Strand, J" uniqKey="Strand J">J. Strand</name></author><author><name sortKey="Selvaraju, R K" uniqKey="Selvaraju R">R.K. Selvaraju</name></author><author><name sortKey="Altai, M" uniqKey="Altai M">M. Altai</name></author><author><name sortKey="Orlova, A" uniqKey="Orlova A">A. Orlova</name></author><author><name sortKey="Eriksson Karlstrom, A" uniqKey="Eriksson Karlstrom A">A. Eriksson Karlström</name></author><author><name sortKey="Tolmachev, V" uniqKey="Tolmachev V">V. Tolmachev</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Pharmaceutics</journal-id><journal-id journal-id-type="iso-abbrev">Pharmaceutics</journal-id><journal-id journal-id-type="publisher-id">pharmaceutics</journal-id><journal-title-group><journal-title>Pharmaceutics</journal-title></journal-title-group><issn pub-type="epub">1999-4923</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31382362</article-id><article-id pub-id-type="pmc">6724035</article-id><article-id pub-id-type="doi">10.3390/pharmaceutics11080380</article-id><article-id pub-id-type="publisher-id">pharmaceutics-11-00380</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Evaluation of Tumor-Targeting Properties of an Antagonistic Bombesin Analogue RM26 Conjugated with a Non-Residualizing Radioiodine Label Comparison with a Radiometal-Labelled Counterpart</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-2660-9837</contrib-id><name><surname>Oroujeni</surname><given-names>Maryam</given-names></name><xref ref-type="aff" rid="af1-pharmaceutics-11-00380">1</xref><xref ref-type="author-notes" rid="fn1-pharmaceutics-11-00380">†</xref></contrib><contrib contrib-type="author"><name><surname>Abouzayed</surname><given-names>Ayman</given-names></name><xref ref-type="aff" rid="af2-pharmaceutics-11-00380">2</xref><xref ref-type="author-notes" rid="fn1-pharmaceutics-11-00380">†</xref></contrib><contrib contrib-type="author"><name><surname>Lundmark</surname><given-names>Fanny</given-names></name><xref ref-type="aff" rid="af2-pharmaceutics-11-00380">2</xref></contrib><contrib contrib-type="author"><name><surname>Mitran</surname><given-names>Bogdan</given-names></name><xref ref-type="aff" rid="af2-pharmaceutics-11-00380">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-6120-2683</contrib-id><name><surname>Orlova</surname><given-names>Anna</given-names></name><xref ref-type="aff" rid="af2-pharmaceutics-11-00380">2</xref><xref ref-type="aff" rid="af3-pharmaceutics-11-00380">3</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-6122-1734</contrib-id><name><surname>Tolmachev</surname><given-names>Vladimir</given-names></name><xref ref-type="aff" rid="af1-pharmaceutics-11-00380">1</xref><xref rid="c1-pharmaceutics-11-00380" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><name><surname>Rosenström</surname><given-names>Ulrika</given-names></name><xref ref-type="aff" rid="af2-pharmaceutics-11-00380">2</xref></contrib></contrib-group><aff id="af1-pharmaceutics-11-00380"><label>1</label>Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden</aff><aff id="af2-pharmaceutics-11-00380"><label>2</label>Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala, Sweden</aff><aff id="af3-pharmaceutics-11-00380"><label>3</label>Science for Life Laboratory, Uppsala University, SE-750 03 Uppsala, Sweden</aff><author-notes><corresp id="c1-pharmaceutics-11-00380"><label>*</label>Correspondence: <email>Vladimir.tolmachev@igp.uu.se</email>; Tel.: +46-070-425-0782</corresp><fn id="fn1-pharmaceutics-11-00380"><label>†</label><p>These authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="epub"><day>02</day><month>8</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>8</month><year>2019</year></pub-date><volume>11</volume><issue>8</issue><elocation-id>380</elocation-id><history><date date-type="received"><day>13</day><month>6</month><year>2019</year></date><date date-type="accepted"><day>24</day><month>7</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 by the authors.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Radiolabelled antagonistic bombesin analogues are successfully used for targeting of gastrin-releasing peptide receptors (GRPR) that are overexpressed in prostate cancer. Internalization of antagonistic bombesin analogues is slow. We hypothesized that the use of a non-residualizing radioiodine label might not affect the tumour uptake but would reduce the retention in normal organs, where radiopharmaceutical would be internalized. To test this hypothesis, tyrosine was conjugated via diethylene glycol linker to N-terminus of an antagonistic bombesin analogue RM26 to form Tyr-PEG<sub>2</sub>-RM26. [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 was used as a control with a residualizing label. Tyr-PEG<sub>2</sub>-RM26 was labelled with <sup>125</sup>I with 95% radiochemical purity and retained binding specificity to GRPR. The IC<sub>50</sub> values for Tyr-PEG<sub>2</sub>-RM26 and DOTA-PEG<sub>2</sub>-RM26 were 1.7 ± 0.3 nM and 3.3 ± 0.5 nM, respectively. The cellular processing of [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 by PC-3 cells showed unusually fast internalization. Biodistribution showed that uptake in pancreas and tumour was GRPR-specific for both radioconjugates. Blood clearance of [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 was appreciably slower and activity accumulation in all organs was significantly higher than for [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26. Tumor uptake of [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 was significantly higher than for [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26, resulting in higher tumour-to-organ ratio for [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 at studied time points. Incorporation of amino acids with hydrophilic side-chains next to tyrosine might overcome the problems associated with the use of tyrosine as a prosthetic group for radioiodination.</p></abstract><kwd-group><kwd>prostate cancer</kwd><kwd>bombesin antagonistic analogue</kwd><kwd>GRPR</kwd><kwd>RM26</kwd><kwd>tyrosine</kwd><kwd>PC-3 xenografts</kwd></kwd-group></article-meta></front><floats-group><fig id="pharmaceutics-11-00380-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Structural formula of (<bold>a</bold>) DOTA-PEG<sub>2</sub>-[D-Phe<sup>6</sup>, Sta<sup>13</sup>, Leu<sup>14</sup>] bombesin[6–14] (DOTA-PEG<sub>2</sub>-RM26); (<bold>b</bold>) Tyrosine-PEG<sub>2</sub>-[D-Phe<sup>6</sup>, Sta<sup>13</sup>, Leu<sup>14</sup>] bombesin[6–14] (Tyr-PEG<sub>2</sub>-RM26).</p></caption><graphic xlink:href="pharmaceutics-11-00380-g001"></graphic></fig><fig id="pharmaceutics-11-00380-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>(<bold>a</bold>) High-performance liquid chromatography (HPLC) chromatogram of Tyr-PEG<sub>2</sub>-RM26 at 280 nm and (<bold>b</bold>) mass spectrum of Tyr-PEG<sub>2</sub>-RM26.</p></caption><graphic xlink:href="pharmaceutics-11-00380-g002"></graphic></fig><fig id="pharmaceutics-11-00380-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>In vitro specificity of [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 to PC-3 and DU-145 cells. Radiolabelled conjugate was added to cultured cells at a concentration of 1 nM. One set of culture dishes was pre-saturated with a 200-fold molar excess of non-labelled NOTA-PEG<sub>4</sub>-RM26 before incubation with the labelled conjugate.</p></caption><graphic xlink:href="pharmaceutics-11-00380-g003"></graphic></fig><fig id="pharmaceutics-11-00380-f004" orientation="portrait" position="float"><label>Figure 4</label><caption><p>Inhibition of [<sup>111</sup>In]In-NOTA-PEG<sub>4</sub>-RM26 binding to PC-3 cells with X-PEG<sub>2</sub>-RM26 (X = tyrosine, DOTA). Data are presented as the mean value of three dishes ± SD.</p></caption><graphic xlink:href="pharmaceutics-11-00380-g004"></graphic></fig><fig id="pharmaceutics-11-00380-f005" orientation="portrait" position="float"><label>Figure 5</label><caption><p>Cellular processing of (<bold>a</bold>) [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 and (<bold>b</bold>) [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 on PC-3. Data are presented as the mean values of three dishes ± SD. Not all error bars are visible due to the small standard deviations.</p></caption><graphic xlink:href="pharmaceutics-11-00380-g005"></graphic></fig><fig id="pharmaceutics-11-00380-f006" orientation="portrait" position="float"><label>Figure 6</label><caption><p>Normalized cell-associated radioactivity of [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 in the presence 20 mM sodium azide/10 mM 2-deoxyglucose, 100 µM Chloroquine, 20 mM ammonium chloride by PC-3 cells during continuous incubation at 37 °C. One set of culture dishes was tested as control.</p></caption><graphic xlink:href="pharmaceutics-11-00380-g006"></graphic></fig><fig id="pharmaceutics-11-00380-f007" orientation="portrait" position="float"><label>Figure 7</label><caption><p>In vivo specificity of (a) [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 and (b) [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 in PC-3 tumour xenograft bearing BALB/C nu/nu at 30 min after injection. Blocking was performed by GRPR saturation with co-injection of non-labelled NOTA-PEG<sub>4</sub>-RM26. Asterisk (*) marks significant (<italic>p</italic> < 0.05) difference. Data are presented as a mean ± SD; <italic>n</italic> = 4. Error bars might not be seen because they are smaller than the symbols.</p></caption><graphic xlink:href="pharmaceutics-11-00380-g007"></graphic></fig><fig id="pharmaceutics-11-00380-f008" orientation="portrait" position="float"><label>Figure 8</label><caption><p>Effect of phosphoramidon (PA) on the biodistribution of [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26. Non-tumour bearing mice as the control group were intravenously injected with 40 pmol of [<sup>125</sup>I]I-Tyr-PEG2-RM26 (30 kBq, 100 μL in PBS) into the tail vein. Another group of mice was injected with same activity with co-injection of PA (15 µL of 20 mg/mL of stock solution, 300 µg).</p></caption><graphic xlink:href="pharmaceutics-11-00380-g008"></graphic></fig><fig id="pharmaceutics-11-00380-f009" orientation="portrait" position="float"><label>Figure 9</label><caption><p>Structures of N-termini containing (<bold>a</bold>) Tyr; (<bold>b</bold>) Tyr-Gln; (<bold>c</bold>) Tyr-Lys; (<bold>d</bold>) Tyr-Gln-Gln; (<bold>e</bold>) Tyr-Gln-Lys and their log P calculated using ChemDraw Ultra.</p></caption><graphic xlink:href="pharmaceutics-11-00380-g009"></graphic></fig><table-wrap id="pharmaceutics-11-00380-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">pharmaceutics-11-00380-t001_Table 1</object-id><label>Table 1</label><caption><p>Biodistribution of [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 and [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 in GRPR-expressing PC-3 tumour xenografted female BALB/C nu/nu mice at three time points (total injected mass of 40 pmol). Data are presented as the mean percentage of injected dose per gram tissue (% ID/g; Mean ± SD; <italic>n</italic> = 4), NM stands for non-measureable.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"></th><th colspan="6" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">Uptake, % ID/g</th></tr><tr><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></th><th colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">0.5 h</th><th colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">3 h</th><th colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">24 h</th></tr></thead><tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">blood</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">10.2 ± 1.5 <sup>a,d,e</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.1 ± 0.8 <sup>a,g,h</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.9 ± 1.5 <sup>b,d,f</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.03 ± 0.00 <sup>b,g,i</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.02 ± 0.00 <sup>c, e, f</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.006 ± 0.002 <sup>c,h,i</sup></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">salivary gland</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6.6 ± 3.7 <sup>a,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.8 ± 0.2 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.0 ± 1.2 <sup>b,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.07 ± 0.02 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">thyroid</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8.2 ± 3.7 <sup>a,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.1 ± 0.5 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.2 ± 1.6 <sup>b,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.1 ± 0.0 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">lung</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9.1 ± 1.2 <sup>a,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.8 ± 0.4 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3.5 ± 1.4 <sup>b,d,f</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.1 ± 0.0 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.2 ± 0.1 <sup>f</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">liver</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8.9 ± 3.1 <sup>a,d,e</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.8 ± 0.2 <sup>a,g,h</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.6 ± 1.1 <sup>b,d,f</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.2 ± 0.0 <sup>b,g,i</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.2 ± 0.0 <sup>c,e,f</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.1 ± 0.0 <sup>c,h,i</sup></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">spleen</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5.4 ± 0.8 <sup>a,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.6 ± 0.2 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.0 ± 0.8 <sup>b,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.1 ± 0.0 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">pancreas</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">10.1 ± 1.2 <sup>a,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6.5 ± 1.4 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.3 ± 0.6 <sup>b,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.2 ± 0.0 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">stomach</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">13.2 ± 7.2 <sup>a,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.9 ± 1.1 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4.6 ± 2.7 <sup>b,d,f</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.4 ± 0.1 <sup>b,g,h</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.1 ± 0.0 <sup>f</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">small intestine</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">7.3 ± 3.0 <sup>a,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.5 ± 0.5 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.8 ± 0.7 <sup>b,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.2 ± 0.1 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">kidney</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">13.2 ± 1.8 <sup>d,e</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9.1 ± 2.9 <sup>g,h</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6.1 ± 1.1 <sup>b,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.4 ± 0.3 <sup>b,f,g,i</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.5 ± 0.3 <sup>c,e,f</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.8 ± 0.2 <sup>c,h,i</sup></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">tumour</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">7.0 ± 0.8 <sup>a,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">13.2 ± 4.8 <sup>a,h</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.1 ± 0.8 <sup>b,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9.6 ± 0.6 <sup>b,i</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3.6 ± 1.3 <sup>h,,i</sup></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">muscle </td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.0 ± 0.0<sup>a,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.4 ± 0.1 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.6 ± 0.3 <sup>b,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.02 ± 0.00 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">bone</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3.8 ± 0.8 <sup>a,d,h</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.6 ± 0.3 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.1 ± 0.5 <sup>b,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.05 ± 0.02 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr></tbody></table><table-wrap-foot><fn><p><sup>a</sup> significant difference (<italic>p</italic> < 0.05) between [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 and [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 at 0.5 h after injection; <sup>b</sup> significant difference (<italic>p</italic> < 0.05) between [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 and [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 at 3 h after injection; <sup>c</sup> significant difference (<italic>p</italic> < 0.05) between [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 and [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 at 24 h after injection; <sup>d</sup> significant difference (<italic>p</italic> < 0.05) between 0.5 h <sup>125</sup>I and 3 h <sup>125</sup>I; <sup>e</sup> significant difference (<italic>p</italic> < 0.05) between 0.5 h <sup>125</sup>I and 24 h <sup>125</sup>I; <sup>f</sup> significant difference (<italic>p</italic> < 0.05) between 3 h <sup>125</sup>I and 24 h <sup>125</sup>I; <sup>g</sup> significant difference (<italic>p</italic> < 0.05) between 0.5 h <sup>111</sup>In and 3 h <sup>111</sup>In; <sup>h</sup> significant difference (<italic>p</italic> < 0.05) between 0.5 h <sup>111</sup>In and 24 h <sup>111</sup>In; <sup>i</sup> significant difference (<italic>p</italic> < 0.05) between 3 h <sup>111</sup>In and 24 h <sup>111</sup>In.</p></fn></table-wrap-foot></table-wrap><table-wrap id="pharmaceutics-11-00380-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">pharmaceutics-11-00380-t002_Table 2</object-id><label>Table 2</label><caption><p>Tumour-to-organ ratios of [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 and [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 in BALB/C nu/nu mice bearing GRPR-expressing PC-3 tumour xenograft at 0.5, 3 and 24 h after injection<sup>;</sup> (Mean ± SD; <italic>n</italic> = 4), NM stands for non-measureable.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"></th><th colspan="6" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">Tumor-to-Organ Ratio</th></tr><tr><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></th><th colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">0.5 h</th><th colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">3 h</th><th colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">24 h</th></tr></thead><tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">blood</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.7 ± 0.0 <sup>a,e</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6.3 ± 1.1 <sup>a,g,h</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.8 ± 0.1 <sup>b,f</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">373 ± 47 <sup>b,g,i</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6 ± 4 <sup>c,e,f</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">672 ± 41 <sup>c,h,i</sup></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">salivary gland</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.3 ± 0.6 <sup>a</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">16.5 ± 3.6 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.2 ± 0.3 <sup>b</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">146 ± 36 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">thyroid</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.0 ± 0.5 <sup>a</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">14.6 ± 5.8 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.2 ± 0.6 <sup>b</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">105 ± 40 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">lung</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.8 ± 0.0 <sup>a,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">7.1 ± 1.8 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.6 ± 0.1 <sup>b,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">123 ± 7 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.0 ± 0.6</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">liver</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.8 ± 0.2 <sup>a</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">16.4 ± 3.8 <sup>a,g,h</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.8 ± 0.2 <sup>b</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">61 ± 3 <sup>b,g,i</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.6 ± 0.5 <sup>c</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">45 ± 8 <sup>c,h,i</sup></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">spleen</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.30 ± 0.2 <sup>a,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">20.8 ± 2.5 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.1 ± 0.1 <sup>b,d</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">119 ± 7 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">pancreas</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.7 ± 0.1 <sup>a</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.0 ± 0.4 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.9 ± 0.1 <sup>b</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">50 ± 6 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">stomach</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.6 ± 0.2 <sup>a</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4.6 ± 1.1 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.5 ± 0.1 <sup>b</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">27 ± 6 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">small intestine</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.1 ± 0.6 <sup>a</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9.0 ± 3.3 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.3 ± 0.4 <sup>b</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">68 ± 35 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">kidney</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.5 ± 0.0 <sup>a,d,e</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.4 ± 0.3 <sup>a,g,h</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.3 ± 0.1 <sup>b,d,f</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4 ± 0 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.10 ± 0.0 <sup>c,e,f,i</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5 ± 1 <sup>c,h,i</sup></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">muscle</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3.6 ± 0.4 <sup>a</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">29.9 ± 6.6 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3.7 ± 0.6 <sup>b</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">428 ± 41 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">bone</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.9 ± 0.2 <sup>a</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">22.8 ± 12.8 <sup>a,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.9 ± 0.3 <sup>b</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">221 ± 110 <sup>b,g</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NM</td></tr></tbody></table><table-wrap-foot><fn><p><sup>a</sup> significant difference (<italic>p</italic> < 0.05) between [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 and [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 at 0.5 h after injection; <sup>b</sup> significant difference (<italic>p</italic> < 0.05) between [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 and [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 at 3 h after injection; <sup>c</sup> significant difference (<italic>p</italic> < 0.05) between [<sup>125</sup>I]I-Tyr-PEG<sub>2</sub>-RM26 and [<sup>111</sup>In]In-DOTA-PEG<sub>2</sub>-RM26 at 24 h after injection; <sup>d</sup> significant difference (<italic>p</italic> < 0.05) between 0.5 h <sup>125</sup>I and 3 h <sup>125</sup>I; <sup>e</sup> significant difference (<italic>p</italic> < 0.05) between 0.5 h <sup>125</sup>I and 24 h <sup>125</sup>I; <sup>f</sup> significant difference (<italic>p</italic> < 0.05) between 3 h <sup>125</sup>I and 24 h <sup>125</sup>I; <sup>g</sup> significant difference (<italic>p</italic> < 0.05) between 0.5 h <sup>111</sup>In and 3 h <sup>111</sup>In; <sup>h</sup> significant difference (<italic>p</italic> < 0.05) between 0.5 h <sup>111</sup>In and 24 h <sup>111</sup>In; <sup>i</sup> significant difference (<italic>p</italic> < 0.05) between 3 h <sup>111</sup>In and 24 h <sup>111</sup>In.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list><country><li>Suède</li></country><region><li>East Middle Sweden</li><li>Svealand</li></region><settlement><li>Uppsala</li></settlement><orgName><li>Université d'Uppsala</li></orgName></list><tree><country name="Suède"><region name="Svealand"><name sortKey="Oroujeni, Maryam" sort="Oroujeni, Maryam" uniqKey="Oroujeni M" first="Maryam" last="Oroujeni">Maryam Oroujeni</name></region><name sortKey="Abouzayed, Ayman" sort="Abouzayed, Ayman" uniqKey="Abouzayed A" first="Ayman" last="Abouzayed">Ayman Abouzayed</name><name sortKey="Lundmark, Fanny" sort="Lundmark, Fanny" uniqKey="Lundmark F" first="Fanny" last="Lundmark">Fanny Lundmark</name><name sortKey="Mitran, Bogdan" sort="Mitran, Bogdan" uniqKey="Mitran B" first="Bogdan" last="Mitran">Bogdan Mitran</name><name sortKey="Orlova, Anna" sort="Orlova, Anna" uniqKey="Orlova A" first="Anna" last="Orlova">Anna Orlova</name><name sortKey="Orlova, Anna" sort="Orlova, Anna" uniqKey="Orlova A" first="Anna" last="Orlova">Anna Orlova</name><name sortKey="Rosenstrom, Ulrika" sort="Rosenstrom, Ulrika" uniqKey="Rosenstrom U" first="Ulrika" last="Rosenström">Ulrika Rosenström</name><name sortKey="Tolmachev, Vladimir" sort="Tolmachev, Vladimir" uniqKey="Tolmachev V" first="Vladimir" last="Tolmachev">Vladimir Tolmachev</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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