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

Molecular Imaging Program at Stanford, Bio-X Program, and Department of Radiology, Stanford University, Stanford, California 94305-5427, USA.
Journal of Nuclear Medicine (Impact Factor: 6.16). 02/2008; 49(1):129-34. DOI: 10.2967/jnumed.106.038836
Source: PubMed


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.
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.
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.
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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Available from: Mangal Dandekar
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    • "Deregulation of MET is associated with transformation and metastatic progression in many cancers, and this has led to research of the MET pathway as a therapeutic target [3] [4]. Anti-MET strategies have been investigated using antibodies [5], decoy receptors [6], and a variety of tyrosine kinase inhibitors (TKIs) [7] [8] [9] [10]. MET is expressed in a variety of tissues including canine osteosarcoma (OS) tumors and cell lines [11]. "
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