The strength of small: Improved targeting of Insulin-like Growth Factor-1 Receptor (IGF-1R) with F(ab')2-R1507 fragments in Ewing sarcomas
Identifieur interne : 000336 ( Main/Repository ); précédent : 000335; suivant : 000337The strength of small: Improved targeting of Insulin-like Growth Factor-1 Receptor (IGF-1R) with F(ab')2-R1507 fragments in Ewing sarcomas
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Abstract
Purpose: To investigate whether F(ab')2-fragments of the monoclonal Insulin-like Growth Factor-1 Receptor (IGF-1R) antibody R1507 (F(ab')2-R1507) can successfully target IGF-1R in Ewing sarcomas (ES). Materials and methods: BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human ES xenografts (EW-5 and EW-8) which previously showed heterogeneous or no uptake of indium-111-labelled R1507 IgG (111In-R1507), respectively. Mice were injected with 111In-F(ab')2-R1507 or 111In-R1507 as a reference. Biodistribution and immuno-SPECT/computed tomography (CT) imaging studies were carried out 2, 4, 8 and 24 h post-injection (p.i.) for 111In-F(ab')2-R1507 and 24 h p.i. for 111In-R1507. Results: Biodistribution studies showed specific accumulation of 111In-F(ab')2-R1507 in EW-5 xenografts from t = 2 h p.i. onwards (3.6 ± 0.2%ID/g at t = 24 h p.i.) and 111In-F(ab')2-R1507 immuno-SPECT showed almost homogeneous intratumoural distribution at t = 24 h p.i. Tumour-to-blood ratios of 111In-F(ab')2-R1507 were significantly higher than those of 111In-R1507 at t = 24 h p.i. (2.4 ± 0.4 versus 0.5 ± 0.1, respectively; p < 0.05). More importantly, 111In-F(ab')2-R1507 also specifically accumulated in EW-8 tumours (3.7 ± 0.7%ID/g at t = 24 h p.i). In both EW-5 and EW-8 tumours, there was a good spatial correlation between IGF-1R expression and 111In-F(ab')2-R1507 tumour distribution. Conclusion: 111In-F(ab')2-R1507 fragments can successfully target IGF-1R in ES models and have superior tumour penetrating and IGF-1R-targeting properties as compared to 111In-R1507. This suggests that anti-IGF-1R therapies in ES and other tumours may be improved by using smaller therapeutic compounds, although further in vivo studies addressing this topic are warranted.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">The strength of small: Improved targeting of Insulin-like Growth Factor-1 Receptor (IGF-1R) with F(ab')<sub>2</sub>-R1507 fragments in Ewing sarcomas</title><author><name sortKey="Fleuren, Emmy D G" uniqKey="Fleuren E">Emmy D. G. Fleuren</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medical Oncology, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>6500 HB Nijmegen</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>6500 HB Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Versleijen Jonkers, Yvonne M H" uniqKey="Versleijen Jonkers Y">Yvonne M. H. Versleijen-Jonkers</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medical Oncology, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>6500 HB Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Heskamp, Sandra" uniqKey="Heskamp S">Sandra Heskamp</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medical Oncology, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>6500 HB Nijmegen</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>6500 HB Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Roeffen, Melissa H S" uniqKey="Roeffen M">Melissa H. S. Roeffen</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medical Oncology, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>6500 HB Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Bouwman, Wilbert H" uniqKey="Bouwman W">Wilbert H. Bouwman</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>6500 HB Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Molkenboer Kuenen, Janneke D M" uniqKey="Molkenboer Kuenen J">Janneke D. M. Molkenboer-Kuenen</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>6500 HB Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Van Laarhoven, Hanneke W M" uniqKey="Van Laarhoven H">Hanneke W. M. Van Laarhoven</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medical Oncology, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>6500 HB Nijmegen</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Medical Oncology, Academic Medical Center, University of Amsterdam, P.O. Box 22660</s1><s2>1100 DD Amsterdam</s2><s3>NLD</s3><sZ>7 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>1100 DD Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Oyen, Wim J G" uniqKey="Oyen W">Wim J. G. Oyen</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>6500 HB Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Boerman, Otto C" uniqKey="Boerman O">Otto C. Boerman</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>6500 HB Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Van Der Graaf, Winette T A" uniqKey="Van Der Graaf W">Winette T. A. Van Der Graaf</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medical Oncology, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>6500 HB Nijmegen</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="inist">13-0276920</idno><date when="2013">2013</date><idno type="stanalyst">PASCAL 13-0276920 INIST</idno><idno type="RBID">Pascal:13-0276920</idno><idno type="wicri:Area/Main/Corpus">000908</idno><idno type="wicri:Area/Main/Repository">000336</idno></publicationStmt><seriesStmt><idno type="ISSN">0959-8049</idno><title level="j" type="abbreviated">Eur. j. cancer : (1990)</title><title level="j" type="main">European journal of cancer : (1990)</title></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cancerology</term><term>Ewing sarcoma</term><term>F(ab′)2-Fragment</term><term>Insulin like growth factor 2</term><term>Photon</term><term>Single photon emission tomography</term><term>Strength</term><term>Targeting</term><term>Type 1 insulin-like growth factor receptor</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Sarcome d'Ewing</term><term>Résistance mécanique</term><term>Ciblage</term><term>Facteur croissance IGF2</term><term>Fragment peptidique F(ab′)2</term><term>Photon</term><term>Tomoscintigraphie émission monophotonique</term><term>Cancérologie</term><term>Récepteur IGF de type 1</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Purpose: To investigate whether F(ab')<sub>2</sub>-fragments of the monoclonal Insulin-like Growth Factor-1 Receptor (IGF-1R) antibody R1507 (F(ab')<sub>2</sub>-R1507) can successfully target IGF-1R in Ewing sarcomas (ES). Materials and methods: BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human ES xenografts (EW-5 and EW-8) which previously showed heterogeneous or no uptake of indium-111-labelled R1507 IgG (<sup>111</sup>In-R1507), respectively. Mice were injected with <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 or <sup>111</sup>In-R1507 as a reference. Biodistribution and immuno-SPECT/computed tomography (CT) imaging studies were carried out 2, 4, 8 and 24 h post-injection (p.i.) for <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 and 24 h p.i. for <sup>111</sup>In-R1507. Results: Biodistribution studies showed specific accumulation of <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 in EW-5 xenografts from t = 2 h p.i. onwards (3.6 ± 0.2%ID/g at t = 24 h p.i.) and <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 immuno-SPECT showed almost homogeneous intratumoural distribution at t = 24 h p.i. Tumour-to-blood ratios of <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 were significantly higher than those of <sup>111</sup>In-R1507 at t = 24 h p.i. (2.4 ± 0.4 versus 0.5 ± 0.1, respectively; p < 0.05). More importantly, <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 also specifically accumulated in EW-8 tumours (3.7 ± 0.7%ID/g at t = 24 h p.i). In both EW-5 and EW-8 tumours, there was a good spatial correlation between IGF-1R expression and <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 tumour distribution. Conclusion: <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 fragments can successfully target IGF-1R in ES models and have superior tumour penetrating and IGF-1R-targeting properties as compared to <sup>111</sup>In-R1507. This suggests that anti-IGF-1R therapies in ES and other tumours may be improved by using smaller therapeutic compounds, although further in vivo studies addressing this topic are warranted.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0959-8049</s0></fA01><fA03 i2="1"><s0>Eur. j. cancer : (1990)</s0></fA03><fA05><s2>49</s2></fA05><fA06><s2>13</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>The strength of small: Improved targeting of Insulin-like Growth Factor-1 Receptor (IGF-1R) with F(ab')<sub>2</sub>-R1507 fragments in Ewing sarcomas</s1></fA08><fA11 i1="01" i2="1"><s1>FLEUREN (Emmy D. G.)</s1></fA11><fA11 i1="02" i2="1"><s1>VERSLEIJEN-JONKERS (Yvonne M. H.)</s1></fA11><fA11 i1="03" i2="1"><s1>HESKAMP (Sandra)</s1></fA11><fA11 i1="04" i2="1"><s1>ROEFFEN (Melissa H. S.)</s1></fA11><fA11 i1="05" i2="1"><s1>BOUWMAN (Wilbert H.)</s1></fA11><fA11 i1="06" i2="1"><s1>MOLKENBOER-KUENEN (Janneke D. M.)</s1></fA11><fA11 i1="07" i2="1"><s1>VAN LAARHOVEN (Hanneke W. M.)</s1></fA11><fA11 i1="08" i2="1"><s1>OYEN (Wim J. G.)</s1></fA11><fA11 i1="09" i2="1"><s1>BOERMAN (Otto C.)</s1></fA11><fA11 i1="10" i2="1"><s1>VAN DER GRAAF (Winette T. A.)</s1></fA11><fA14 i1="01"><s1>Department of Medical Oncology, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101</s1><s2>6500 HB Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></fA14><fA14 i1="03"><s1>Department of Medical Oncology, Academic Medical Center, University of Amsterdam, P.O. Box 22660</s1><s2>1100 DD Amsterdam</s2><s3>NLD</s3><sZ>7 aut.</sZ></fA14><fA20><s1>2851-2858</s1></fA20><fA21><s1>2013</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>12648</s2><s5>354000501928980100</s5></fA43><fA44><s0>0000</s0><s1>© 2013 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>37 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>13-0276920</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>European journal of cancer : (1990)</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>Purpose: To investigate whether F(ab')<sub>2</sub>-fragments of the monoclonal Insulin-like Growth Factor-1 Receptor (IGF-1R) antibody R1507 (F(ab')<sub>2</sub>-R1507) can successfully target IGF-1R in Ewing sarcomas (ES). Materials and methods: BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human ES xenografts (EW-5 and EW-8) which previously showed heterogeneous or no uptake of indium-111-labelled R1507 IgG (<sup>111</sup>In-R1507), respectively. Mice were injected with <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 or <sup>111</sup>In-R1507 as a reference. Biodistribution and immuno-SPECT/computed tomography (CT) imaging studies were carried out 2, 4, 8 and 24 h post-injection (p.i.) for <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 and 24 h p.i. for <sup>111</sup>In-R1507. Results: Biodistribution studies showed specific accumulation of <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 in EW-5 xenografts from t = 2 h p.i. onwards (3.6 ± 0.2%ID/g at t = 24 h p.i.) and <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 immuno-SPECT showed almost homogeneous intratumoural distribution at t = 24 h p.i. Tumour-to-blood ratios of <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 were significantly higher than those of <sup>111</sup>In-R1507 at t = 24 h p.i. (2.4 ± 0.4 versus 0.5 ± 0.1, respectively; p < 0.05). More importantly, <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 also specifically accumulated in EW-8 tumours (3.7 ± 0.7%ID/g at t = 24 h p.i). In both EW-5 and EW-8 tumours, there was a good spatial correlation between IGF-1R expression and <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 tumour distribution. Conclusion: <sup>111</sup>In-F(ab')<sub>2</sub>-R1507 fragments can successfully target IGF-1R in ES models and have superior tumour penetrating and IGF-1R-targeting properties as compared to <sup>111</sup>In-R1507. This suggests that anti-IGF-1R therapies in ES and other tumours may be improved by using smaller therapeutic compounds, although further in vivo studies addressing this topic are warranted.</s0></fC01><fC02 i1="01" i2="X"><s0>002B02</s0></fC02><fC02 i1="02" i2="X"><s0>002B04C</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Sarcome d'Ewing</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Ewing sarcoma</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Sarcoma Ewing</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Résistance mécanique</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Strength</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Resistencia mecánica</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Ciblage</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Targeting</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Blancado</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Facteur croissance IGF2</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Insulin like growth factor 2</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Factor crecimiento IGF2</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Fragment peptidique F(ab′)2</s0><s5>06</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>F(ab′)2-Fragment</s0><s5>06</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Fragmento peptídico F(ab′)2</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Photon</s0><s5>08</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Photon</s0><s5>08</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Fotón</s0><s5>08</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Tomoscintigraphie émission monophotonique</s0><s5>09</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Single photon emission tomography</s0><s5>09</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Tomografía emisión fotón único</s0><s5>09</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Cancérologie</s0><s5>11</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Cancerology</s0><s5>11</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Cancerología</s0><s5>11</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Récepteur IGF de type 1</s0><s4>CD</s4><s5>96</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Type 1 insulin-like growth factor receptor</s0><s4>CD</s4><s5>96</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Pathologie du système ostéoarticulaire</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Diseases of the osteoarticular system</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Sistema osteoarticular patología</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Tumeur maligne</s0><s2>NM</s2><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Malignant tumor</s0><s2>NM</s2><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Tumor maligno</s0><s2>NM</s2><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Cancer</s0><s2>NM</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Cancer</s0><s2>NM</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Cáncer</s0><s2>NM</s2></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Exploration radioisotopique</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Radionuclide study</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Exploración radioisotópica</s0><s5>39</s5></fC07><fN21><s1>259</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= The strength of small: Improved targeting of Insulin-like Growth Factor-1 Receptor (IGF-1R) with F(ab')2-R1507 fragments in Ewing sarcomas
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