Preclinical Efficacy of the c-Met Inhibitor CE-355621 in a U87 MG Mouse Xenograft Model Evaluated by ^sup 18^F-FDG Small-Animal PET

• Published in: The Journal of nuclear medicine (1978) Vol. 49; no. 1; p. 129
• Main Authors: Tseng, Jeffrey R, Kang, Keon Wook, Dandekar, Mangal, Yaghoubi, Shahriar, Lee, Joseph H, Christensen, James G, Muir, Stephen, Vincent, Patrick W, Michaud, Neil R, Gambhir, Sanjiv S
• Format: Journal Article
• Language: English
• Published: New York Society of Nuclear Medicine 01.01.2008
• Subjects: Apoptosis; Carbon dioxide; Cell adhesion & migration; Clinical trials; Immunization; Laboratory animals; Monoclonal antibodies; Novels; Rodents; Studies; Substance abuse treatment
• ISSN: 0161-5505

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 ^sup 18^F-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 ^sup 18^F-FDG small-animal PET and compared with tumor volume growth curves. Results: The maximum %ID/g (percentage injected dose per gram of tissue) of ^sup 18^F-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 ^sup 18^F-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 ^sup 18^F-FDG accumulation earlier than tumor volume changes in a mouse xenograft model. These results support the use of ^sup 18^F-FDG PET to assess early tumor response for CE-355621. [PUBLICATION ABSTRACT]