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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

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; and ⁶ Department of Bioengineering, Stanford University, Stanford, California

Correspondence: For correspondence or reprints contact: Sanjiv S. Gambhir, MD, PhD, Molecular Imaging Program at Stanford (MIPS), Division of Nuclear Medicine, Departments of Radiology and Bioengineering, Bio-X Program; The James H. Clark Center, 318 Campus Dr., East Wing, 1st Floor, Stanford, California 94305-5427. E-mail: sgambhir{at}stanford.edu

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

^* Contributed equally to this work.

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.

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