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Meeting ReportOncology-Basic: Translational/Preclinical Nuclear Medicine

Optimization of MORAb-009 dose to block shed antigen in circulation and produce high tumor to background ratios of In-111 MORAb-009

In Soo Shin, Hyung Sub Kim, Zhengsheng Yao, Sang-Myung Lee, Celeste Regino, Noriko Sato, Raffit Hassan, Peter Choyke, Ira Pastan and Chang Paik
Journal of Nuclear Medicine May 2010, 51 (supplement 2) 1192;
In Soo Shin
1NMD, Radiology and Imaging Science, CC, NIH, Bethesda, MD
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Hyung Sub Kim
1NMD, Radiology and Imaging Science, CC, NIH, Bethesda, MD
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Zhengsheng Yao
1NMD, Radiology and Imaging Science, CC, NIH, Bethesda, MD
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Sang-Myung Lee
1NMD, Radiology and Imaging Science, CC, NIH, Bethesda, MD
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Celeste Regino
2Molecular Imaging Program, NCI, NIH, Bethesda, MD
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Noriko Sato
2Molecular Imaging Program, NCI, NIH, Bethesda, MD
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Raffit Hassan
3Laboratory of Molecular Biology, NCI, NIH, Bethesda, MD
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Peter Choyke
2Molecular Imaging Program, NCI, NIH, Bethesda, MD
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Ira Pastan
3Laboratory of Molecular Biology, NCI, NIH, Bethesda, MD
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Chang Paik
1NMD, Radiology and Imaging Science, CC, NIH, Bethesda, MD
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Abstract

1192

Objectives We are studying the in vivo tumor targeting and biodistribution of In-111 labeled MORAb-009, a mAb directed against mesothelin, in nude mice with mesothelin-expressing A431/K5. Our aims are to determine the optimum dose of MORAb-009 to block shed-mesothelin in the blood and extracellular fluid (ECF) and to produce a high tumor-to-non-tumor background radioactivity ratio using In-111 MORAb-009.

Methods Groups of nude mice (n = 5-10 mice/group) were inoculated in the right hind flank s.c. with A431/K5 tumor cells expressing mesothelin. A week later, the mice received i.v. In-111-CHX-A”- MORAb-009 (2 μCi /2~50 μg mAb). The mice were euthanized at 1, 2, and 5 day postinjection for biodistributon.

Results The results indicate that the tumor uptake (% ID/g) was inversely proportional to the liver and spleen uptake of In-111 MORAb-009. For a MORAb-009 dose ranging from 2 to 50 μg and a tumor size raging from ~30 mg to > 400 mg, we found that the tumor uptake was inversely proportional to tumor size and that the tumor uptake of a smaller MORAb-009 dose (2 µg) was greatly affected by tumor size; 30 µg MORAb-009 produced a high tumor uptake and retention (27.6 ± 7.1% and 36.5 ± 14.9% injected dose (ID)/g tumor at 1 and 5 day, respectively) of In-111 MORAb-009 in mice with < ~130 mg tumors, and 50 µg MORAb-009 produced a high tumor uptake and retention (26.3 ± 9.9% and 29.4 ± 11.9% ID/g at 1 and 5 day, respectively) in mice with < ~240 mg tumors.

Conclusions These results indicate that without pre- or co-injection of an optimal dose of MORAb-009, some of In-111 MORAb-009 could bind to shed-mesothelin in the blood before reaching the tumor and form MORAb-009-mesothelin complexes which would be taken up by the liver and spleen, thereby decreasing the tumor uptake of In-111 MORAb-009 and exposing these organs to associated radiation

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Journal of Nuclear Medicine
Vol. 51, Issue supplement 2
May 2010
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Optimization of MORAb-009 dose to block shed antigen in circulation and produce high tumor to background ratios of In-111 MORAb-009
In Soo Shin, Hyung Sub Kim, Zhengsheng Yao, Sang-Myung Lee, Celeste Regino, Noriko Sato, Raffit Hassan, Peter Choyke, Ira Pastan, Chang Paik
Journal of Nuclear Medicine May 2010, 51 (supplement 2) 1192;

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Optimization of MORAb-009 dose to block shed antigen in circulation and produce high tumor to background ratios of In-111 MORAb-009
In Soo Shin, Hyung Sub Kim, Zhengsheng Yao, Sang-Myung Lee, Celeste Regino, Noriko Sato, Raffit Hassan, Peter Choyke, Ira Pastan, Chang Paik
Journal of Nuclear Medicine May 2010, 51 (supplement 2) 1192;
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