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First published online December 12, 2007
J Nucl Med 2007, doi:10.2967/jnumed.106.038836
 © 2007 by Society of Nuclear Medicine
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Preclinical Efficacy of the c-Met Inhibitor CE-355621 in a U87 MG Mouse Xenograft Model Evaluated by 18F-FDG Small-Animal PET

Jeffrey R. Tseng 1, * Keon Wook Kang 2, * Mangal Dandekar 1, Shahriar Yaghoubi 1, Joseph H. Lee 3, James G. Christensen 3, Stephen Muir 4, Patrick W. Vincent 5, Neil R. Michaud 5, and Sanjiv S. Gambhir 6*

1 Molecular Imaging Program at Stanford, Bio-X Program, and Department of Radiology, Stanford University, Stanford, California
2 Department of Nuclear Medicine, National Cancer Center, Goyang, South Korea
3 Cancer Biology, PGRD-La Jolla Laboratories, Pfizer Inc., La Jolla, California
4 Oncology, PGRD-New London, Pfizer, Inc., New London, Connecticut
5 Cancer Biology, PGRD-Groton Laboratories, Pfizer Inc., Groton, Connecticut
6 Molecular Imaging Program at Stanford, Bio-X Program, and Department of Radiology, Stanford University, Stanford, California; Department of Bioengineering, Stanford University, Stanford, California

* To whom correspondence should be addressed. E-mail: sgambhir{at}stanford.edu.


  Abstract

The purpose of this study was to evaluate the efficacy of CE-355621, a novel antibody against c-Met, in a subcutaneous U87 MG xenograft mouse model using 18F-FDG small-animal PET. Methods: CE-355621 or control vehicle was administered intraperitoneally into nude mice (drug-treated group, n = 12; control group, n = 14) with U87 MG subcutaneous tumor xenografts. Drug efficacy was evaluated over 2 wk using 18F-FDG small-animal PET and compared with tumor volume growth curves. Results: The maximum %ID/g (percentage injected dose per gram of tissue) of 18F-FDG accumulation in mice treated with CE-355621 remained essentially unchanged over 2 wk, whereas the %ID/g of the control tumors increased 66% compared with the baseline. Significant inhibition of 18F-FDG accumulation was seen 3 d after drug treatment, which was earlier than the inhibition of tumor volume growth seen at 7 d after drug treatment. Conclusion: CE-355621 is an efficacious novel antineoplastic chemotherapeutic agent that inhibits 18F-FDG accumulation earlier than tumor volume changes in a mouse xenograft model. These results support the use of 18F-FDG PET to assess early tumor response for CE-355621.

Key Words: CE-355621, c-Met inhibitor, 18F-FDG, microPET, drug evaluation, therapy response




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