Radioactive Holmium Acetylacetonate Microspheres for Interstitial Microbrachytherapy: An In Vitro and In Vivo Stability Study
Identifieur interne : 000A50 ( Main/Exploration ); précédent : 000A49; suivant : 000A51Radioactive Holmium Acetylacetonate Microspheres for Interstitial Microbrachytherapy: An In Vitro and In Vivo Stability Study
Auteurs : Wouter Bult [Pays-Bas] ; Hendrik De Leeuw [Pays-Bas] ; Olav M. Steinebach [Pays-Bas] ; Martijn J. Van Der Bom [Pays-Bas] ; Hubert Th. Wolterbeek [Pays-Bas] ; Ron M. A. Heeren [Pays-Bas] ; Chris J. G. Bakker [Pays-Bas] ; Alfred D. Van Het Schip [Pays-Bas] ; Wim E. Hennink [Pays-Bas] ; J. Frank W. Nijsen [Pays-Bas]Source :
- Pharmaceutical Research [ 0724-8741 ] ; 2011.
Abstract
The clinical application of holmium acetylacetonate microspheres (HoAcAcMS) for the intratumoral radionuclide treatment of solid malignancies requires a thorough understanding of their stability. Therefore, an
HoAcAcMS, before and after neutron irradiation, were incubated in a phosphate buffer at 37°C for 6 months. The
After 4 days in buffer the acetylacetonate ligands were replaced by phosphate, without altering the particle size and surface morphology. HoAcAcMS before and after neutron irradiation were administered intratumorally in VX2 tumor-bearing rabbits. No holmium was detected in the faeces, urine, femur and blood. Histological examination of the tumor revealed clusters of intact microspheres amidst necrotic tissue after 30 days.
HoAcAcMS are stable both
Url:
DOI: 10.1007/s11095-011-0610-7
PubMed: 22068276
PubMed Central: 3281200
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Radioactive Holmium Acetylacetonate Microspheres for Interstitial Microbrachytherapy: An <italic>In Vitro</italic> and <italic>In Vivo</italic> Stability Study</title><author><name sortKey="Bult, Wouter" sort="Bult, Wouter" uniqKey="Bult W" first="Wouter" last="Bult">Wouter Bult</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="De Leeuw, Hendrik" sort="De Leeuw, Hendrik" uniqKey="De Leeuw H" first="Hendrik" last="De Leeuw">Hendrik De Leeuw</name><affiliation wicri:level="3"><nlm:aff id="Aff2">Image Sciences Institute, UMC Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Image Sciences Institute, UMC Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Steinebach, Olav M" sort="Steinebach, Olav M" uniqKey="Steinebach O" first="Olav M." last="Steinebach">Olav M. Steinebach</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Department of Radiation, Radionuclides and Reactors Section Radiation & Isotopes for Health, Delft University of Technology, Delft, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Radiation, Radionuclides and Reactors Section Radiation & Isotopes for Health, Delft University of Technology, Delft</wicri:regionArea><wicri:noRegion>Delft</wicri:noRegion></affiliation></author><author><name sortKey="Van Der Bom, Martijn J" sort="Van Der Bom, Martijn J" uniqKey="Van Der Bom M" first="Martijn J." last="Van Der Bom">Martijn J. Van Der Bom</name><affiliation wicri:level="3"><nlm:aff id="Aff2">Image Sciences Institute, UMC Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Image Sciences Institute, UMC Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Wolterbeek, Hubert Th" sort="Wolterbeek, Hubert Th" uniqKey="Wolterbeek H" first="Hubert Th." last="Wolterbeek">Hubert Th. Wolterbeek</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Department of Radiation, Radionuclides and Reactors Section Radiation & Isotopes for Health, Delft University of Technology, Delft, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Radiation, Radionuclides and Reactors Section Radiation & Isotopes for Health, Delft University of Technology, Delft</wicri:regionArea><wicri:noRegion>Delft</wicri:noRegion></affiliation></author><author><name sortKey="Heeren, Ron M A" sort="Heeren, Ron M A" uniqKey="Heeren R" first="Ron M. A." last="Heeren">Ron M. A. Heeren</name><affiliation wicri:level="3"><nlm:aff id="Aff4">FOM institute for Atomic and Molecular Physics, Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>FOM institute for Atomic and Molecular Physics, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Bakker, Chris J G" sort="Bakker, Chris J G" uniqKey="Bakker C" first="Chris J. G." last="Bakker">Chris J. G. Bakker</name><affiliation wicri:level="3"><nlm:aff id="Aff2">Image Sciences Institute, UMC Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Image Sciences Institute, UMC Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Van Het Schip, Alfred D" sort="Van Het Schip, Alfred D" uniqKey="Van Het Schip A" first="Alfred D." last="Van Het Schip">Alfred D. Van Het Schip</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Hennink, Wim E" sort="Hennink, Wim E" uniqKey="Hennink W" first="Wim E." last="Hennink">Wim E. Hennink</name><affiliation wicri:level="3"><nlm:aff id="Aff5">Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences Utrecht University, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Nijsen, J Frank W" sort="Nijsen, J Frank W" uniqKey="Nijsen J" first="J. Frank W." last="Nijsen">J. Frank W. Nijsen</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22068276</idno><idno type="pmc">3281200</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281200</idno><idno type="RBID">PMC:3281200</idno><idno type="doi">10.1007/s11095-011-0610-7</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000182</idno><idno type="wicri:Area/Pmc/Curation">000182</idno><idno type="wicri:Area/Pmc/Checkpoint">000353</idno><idno type="wicri:Area/Ncbi/Merge">000115</idno><idno type="wicri:Area/Ncbi/Curation">000115</idno><idno type="wicri:Area/Ncbi/Checkpoint">000115</idno><idno type="wicri:doubleKey">0724-8741:2011:Bult W:radioactive:holmium:acetylacetonate</idno><idno type="wicri:Area/Main/Merge">000A52</idno><idno type="wicri:Area/Main/Curation">000A50</idno><idno type="wicri:Area/Main/Exploration">000A50</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Radioactive Holmium Acetylacetonate Microspheres for Interstitial Microbrachytherapy: An <italic>In Vitro</italic> and <italic>In Vivo</italic> Stability Study</title><author><name sortKey="Bult, Wouter" sort="Bult, Wouter" uniqKey="Bult W" first="Wouter" last="Bult">Wouter Bult</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="De Leeuw, Hendrik" sort="De Leeuw, Hendrik" uniqKey="De Leeuw H" first="Hendrik" last="De Leeuw">Hendrik De Leeuw</name><affiliation wicri:level="3"><nlm:aff id="Aff2">Image Sciences Institute, UMC Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Image Sciences Institute, UMC Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Steinebach, Olav M" sort="Steinebach, Olav M" uniqKey="Steinebach O" first="Olav M." last="Steinebach">Olav M. Steinebach</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Department of Radiation, Radionuclides and Reactors Section Radiation & Isotopes for Health, Delft University of Technology, Delft, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Radiation, Radionuclides and Reactors Section Radiation & Isotopes for Health, Delft University of Technology, Delft</wicri:regionArea><wicri:noRegion>Delft</wicri:noRegion></affiliation></author><author><name sortKey="Van Der Bom, Martijn J" sort="Van Der Bom, Martijn J" uniqKey="Van Der Bom M" first="Martijn J." last="Van Der Bom">Martijn J. Van Der Bom</name><affiliation wicri:level="3"><nlm:aff id="Aff2">Image Sciences Institute, UMC Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Image Sciences Institute, UMC Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Wolterbeek, Hubert Th" sort="Wolterbeek, Hubert Th" uniqKey="Wolterbeek H" first="Hubert Th." last="Wolterbeek">Hubert Th. Wolterbeek</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Department of Radiation, Radionuclides and Reactors Section Radiation & Isotopes for Health, Delft University of Technology, Delft, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Radiation, Radionuclides and Reactors Section Radiation & Isotopes for Health, Delft University of Technology, Delft</wicri:regionArea><wicri:noRegion>Delft</wicri:noRegion></affiliation></author><author><name sortKey="Heeren, Ron M A" sort="Heeren, Ron M A" uniqKey="Heeren R" first="Ron M. A." last="Heeren">Ron M. A. Heeren</name><affiliation wicri:level="3"><nlm:aff id="Aff4">FOM institute for Atomic and Molecular Physics, Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>FOM institute for Atomic and Molecular Physics, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Bakker, Chris J G" sort="Bakker, Chris J G" uniqKey="Bakker C" first="Chris J. G." last="Bakker">Chris J. G. Bakker</name><affiliation wicri:level="3"><nlm:aff id="Aff2">Image Sciences Institute, UMC Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Image Sciences Institute, UMC Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Van Het Schip, Alfred D" sort="Van Het Schip, Alfred D" uniqKey="Van Het Schip A" first="Alfred D." last="Van Het Schip">Alfred D. Van Het Schip</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Hennink, Wim E" sort="Hennink, Wim E" uniqKey="Hennink W" first="Wim E." last="Hennink">Wim E. Hennink</name><affiliation wicri:level="3"><nlm:aff id="Aff5">Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences Utrecht University, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Nijsen, J Frank W" sort="Nijsen, J Frank W" uniqKey="Nijsen J" first="J. Frank W." last="Nijsen">J. Frank W. Nijsen</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author></analytic><series><title level="j">Pharmaceutical Research</title><idno type="ISSN">0724-8741</idno><idno type="eISSN">1573-904X</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><sec><title>Purpose</title><p>The clinical application of holmium acetylacetonate microspheres (HoAcAcMS) for the intratumoral radionuclide treatment of solid malignancies requires a thorough understanding of their stability. Therefore, an <italic>in vitro</italic> and an <italic>in vivo</italic> stability study with HoAcAcMS was conducted.</p></sec><sec><title>Methods</title><p>HoAcAcMS, before and after neutron irradiation, were incubated in a phosphate buffer at 37°C for 6 months. The <italic>in vitro</italic> release of holmium in this buffer after 6 months was 0.5%. Elemental analysis, scanning electron microscopy, infrared spectroscopy and time of flight secondary ion mass spectrometry were performed on the HoAcAcMS.</p></sec><sec><title>Results</title><p>After 4 days in buffer the acetylacetonate ligands were replaced by phosphate, without altering the particle size and surface morphology. HoAcAcMS before and after neutron irradiation were administered intratumorally in VX2 tumor-bearing rabbits. No holmium was detected in the faeces, urine, femur and blood. Histological examination of the tumor revealed clusters of intact microspheres amidst necrotic tissue after 30 days.</p></sec><sec><title>Conclusion</title><p>HoAcAcMS are stable both <italic>in vitro</italic> and <italic>in vivo</italic> and are suitable for intratumoral radionuclide treatment.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Jemal, A" uniqKey="Jemal A">A Jemal</name></author><author><name sortKey="Siegel, R" uniqKey="Siegel R">R Siegel</name></author><author><name sortKey="Ward, E" uniqKey="Ward E">E Ward</name></author><author><name sortKey="Hao, Y" uniqKey="Hao Y">Y Hao</name></author><author><name sortKey="Xu, J" uniqKey="Xu J">J Xu</name></author><author><name sortKey="Thun, Mj" uniqKey="Thun M">MJ Thun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Parkin, Dm" uniqKey="Parkin D">DM Parkin</name></author><author><name sortKey="Bray, F" uniqKey="Bray F">F 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uniqKey="Meulenhoff P">PC Meulenhoff</name></author><author><name sortKey="Zonnenberg, Ba" uniqKey="Zonnenberg B">BA Zonnenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bult, W" uniqKey="Bult W">W Bult</name></author><author><name sortKey="Varkevisser, R" uniqKey="Varkevisser R">R Varkevisser</name></author><author><name sortKey="Soulimani, F" uniqKey="Soulimani F">F Soulimani</name></author><author><name sortKey="Seevinck, Pr" uniqKey="Seevinck P">PR Seevinck</name></author><author><name sortKey="Leeuw, H" uniqKey="Leeuw H">H Leeuw</name></author><author><name sortKey="Bakker, Cj" uniqKey="Bakker C">CJ Bakker</name></author><author><name sortKey="Luijten, Pr" uniqKey="Luijten P">PR Luijten</name></author><author><name sortKey="Schip, Ad" uniqKey="Schip A">AD Schip</name></author><author><name sortKey="Hennink, We" uniqKey="Hennink W">WE Hennink</name></author><author><name sortKey="Nijsen, Jf" uniqKey="Nijsen J">JF Nijsen</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Dong, X" uniqKey="Dong X">X Dong</name></author><author><name sortKey="Gusev, A" uniqKey="Gusev A">A Gusev</name></author><author><name sortKey="Hercules, Dm" uniqKey="Hercules D">DM Hercules</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Rouxel, J" uniqKey="Rouxel J">J Rouxel</name></author><author><name sortKey="Tournoux, M" uniqKey="Tournoux M">M Tournoux</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, C" uniqKey="Lu C">C Lu</name></author><author><name sortKey="Ding, Zf" uniqKey="Ding Z">ZF Ding</name></author><author><name sortKey="Lipson, Rh" uniqKey="Lipson R">RH Lipson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harlan, Cj" uniqKey="Harlan C">CJ Harlan</name></author><author><name sortKey="Kareiva, A" uniqKey="Kareiva A">A Kareiva</name></author><author><name sortKey="Macqueen, Db" uniqKey="Macqueen D">DB MacQueen</name></author><author><name sortKey="Cook, R" uniqKey="Cook R">R Cook</name></author><author><name sortKey="Barron, Ar" uniqKey="Barron A">AR Barron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suzuki, Ys" uniqKey="Suzuki Y">YS Suzuki</name></author><author><name sortKey="Momose, Y" uniqKey="Momose Y">Y Momose</name></author><author><name sortKey="Higashi, N" uniqKey="Higashi N">N Higashi</name></author><author><name sortKey="Shigematsu, A" uniqKey="Shigematsu A">A Shigematsu</name></author><author><name sortKey="Park, Kb" uniqKey="Park K">KB Park</name></author><author><name sortKey="Kim, Ym" uniqKey="Kim Y">YM Kim</name></author><author><name sortKey="Kim, Jr" uniqKey="Kim J">JR Kim</name></author><author><name sortKey="Ryu, Jm" uniqKey="Ryu J">JM Ryu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sinton, Tj" uniqKey="Sinton T">TJ Sinton</name></author><author><name sortKey="Cowley, Dm" uniqKey="Cowley D">DM Cowley</name></author><author><name sortKey="Bryant, Sj" uniqKey="Bryant S">SJ Bryant</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vente, Mad" uniqKey="Vente M">MAD Vente</name></author><author><name sortKey="Nijsen, Jfw" uniqKey="Nijsen J">JFW Nijsen</name></author><author><name sortKey="Wit, Tc" uniqKey="Wit T">TC Wit</name></author><author><name sortKey="Seppenwoolde, Jh" uniqKey="Seppenwoolde J">JH Seppenwoolde</name></author><author><name sortKey="Krijger, Gc" uniqKey="Krijger G">GC Krijger</name></author><author><name sortKey="Seevinck, Pr" uniqKey="Seevinck P">PR Seevinck</name></author><author><name sortKey="Huisman, A" uniqKey="Huisman A">A Huisman</name></author><author><name sortKey="Zonnenberg, Ba" uniqKey="Zonnenberg B">BA Zonnenberg</name></author><author><name sortKey="Ingh, Tsgam" uniqKey="Ingh T">TSGAM Ingh</name></author><author><name sortKey="Schip, Ad" uniqKey="Schip A">AD Schip</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Salem, R" uniqKey="Salem R">R Salem</name></author><author><name sortKey="Thurston, Kg" uniqKey="Thurston K">KG Thurston</name></author><author><name sortKey="Carr, Bi" uniqKey="Carr B">BI Carr</name></author><author><name sortKey="Goin, Je" uniqKey="Goin J">JE Goin</name></author><author><name sortKey="Geschwind, Jf" uniqKey="Geschwind J">JF Geschwind</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Durbin, Pw" uniqKey="Durbin P">PW Durbin</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Pays-Bas</li></country><region><li>Hollande-Septentrionale</li><li>Utrecht (province)</li></region><settlement><li>Amsterdam</li><li>Utrecht</li></settlement></list><tree><country name="Pays-Bas"><region name="Utrecht (province)"><name sortKey="Bult, Wouter" sort="Bult, Wouter" uniqKey="Bult W" first="Wouter" last="Bult">Wouter Bult</name></region><name sortKey="Bakker, Chris J G" sort="Bakker, Chris J G" uniqKey="Bakker C" first="Chris J. G." last="Bakker">Chris J. G. Bakker</name><name sortKey="De Leeuw, Hendrik" sort="De Leeuw, Hendrik" uniqKey="De Leeuw H" first="Hendrik" last="De Leeuw">Hendrik De Leeuw</name><name sortKey="Heeren, Ron M A" sort="Heeren, Ron M A" uniqKey="Heeren R" first="Ron M. A." last="Heeren">Ron M. A. Heeren</name><name sortKey="Hennink, Wim E" sort="Hennink, Wim E" uniqKey="Hennink W" first="Wim E." last="Hennink">Wim E. Hennink</name><name sortKey="Nijsen, J Frank W" sort="Nijsen, J Frank W" uniqKey="Nijsen J" first="J. Frank W." last="Nijsen">J. Frank W. Nijsen</name><name sortKey="Steinebach, Olav M" sort="Steinebach, Olav M" uniqKey="Steinebach O" first="Olav M." last="Steinebach">Olav M. Steinebach</name><name sortKey="Van Der Bom, Martijn J" sort="Van Der Bom, Martijn J" uniqKey="Van Der Bom M" first="Martijn J." last="Van Der Bom">Martijn J. Van Der Bom</name><name sortKey="Van Het Schip, Alfred D" sort="Van Het Schip, Alfred D" uniqKey="Van Het Schip A" first="Alfred D." last="Van Het Schip">Alfred D. Van Het Schip</name><name sortKey="Wolterbeek, Hubert Th" sort="Wolterbeek, Hubert Th" uniqKey="Wolterbeek H" first="Hubert Th." last="Wolterbeek">Hubert Th. Wolterbeek</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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