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


CONCLUSIONS
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.
Tseng
Jeffrey R
JR
Molecular Imaging Program at Stanford, Bio-X Program, and Department of Radiology, Stanford University, Stanford, California.
Kang
Keon Wook
KW
Department of Nuclear Medicine, National Cancer Center, Goyang, South Korea.
Dandekar
Mangal
M
Molecular Imaging Program at Stanford, Bio-X Program, and Department of Radiology, Stanford University, Stanford, California.
Yaghoubi
Shahriar
S
Molecular Imaging Program at Stanford, Bio-X Program, and Department of Radiology, Stanford University, Stanford, California.
Lee
Joseph H
JH
Cancer Biology, PGRD-La Jolla Laboratories, Pfizer Inc., La Jolla, California.
Christensen
James G
JG
Cancer Biology, PGRD-La Jolla Laboratories, Pfizer Inc., La Jolla, California.
Muir
Stephen
S
Oncology, PGRD-New London, Pfizer, Inc., New London, Connecticut.
Vincent
Patrick W
PW
Cancer Biology, PGRD-Groton Laboratories, Pfizer Inc., Groton, Connecticut.
Michaud
Neil R
NR
Cancer Biology, PGRD-Groton Laboratories, Pfizer Inc., Groton, Connecticut.
Gambhir
Sanjiv S
SS
Molecular Imaging Program at Stanford, Bio-X Program, and Department of Radiology, Stanford University, Stanford, California.|Department of Bioengineering, Stanford University, Stanford, California.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004336:Drug Antagonism; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005909:Glioblastoma; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography / Q000379:methods; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D019859:Proto-Oncogene Proteins c-met