Preclinical efficacy of the c-Met inhibitor CE-355621 in a U87 MG mouse xenograft model evaluated by 18F-FDG small-animal PET

J Nucl Med. 2008 Jan;49(1):129-134. doi: 10.2967/jnumed.106.038836. Epub 2007 Dec 12.

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 (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 (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 (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 (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 (18)F-FDG accumulation earlier than tumor volume changes in a mouse xenograft model. These results support the use of (18)F-FDG PET to assess early tumor response for CE-355621.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Drug Antagonism
  • Fluorodeoxyglucose F18 / pharmacokinetics*
  • Glioblastoma
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Positron-Emission Tomography / methods
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Radiopharmaceuticals / pharmacokinetics*
  • Transplantation, Heterologous

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Proto-Oncogene Proteins c-met