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.
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 ,  Sanjiv S Gambhir  1  6
Affiliations
  • 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. Department of Bioengineering, Stanford University, Stanford, California.
  • # Contributed equally.
PMID: 18077531 DOI: 10.2967/jnumed.106.038836
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.

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