Evaluation of the antitumor effects of rilotumumab by PET imaging in a U-87 MG mouse xenograft model |
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| Authors: | Karen Rex Xiaoman Z Lewis Sundaresan Gobalakrishnan Charles Glaus Matthew D Silva Robert Radinsky Teresa L Burgess Sanjiv S Gambhir Angela Coxon |
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| Institution: | 1. Oncology Research, Amgen Inc., Thousand Oaks, CA, USA;2. Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA;3. Research Imaging Sciences, Amgen Inc., Thousand Oaks, CA, USA;4. Department of Molecular, Cell, and Developmental Biology, University of California at Santa Barbara, Santa Barbara, CA, USA;5. Division of Nuclear Medicine, Department of Radiology and Bio-X Program, Stanford University School of Medicine, Stanford, CA, USA |
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| Abstract: | IntroductionDysregulation of the hepatocyte growth factor (HGF)/MET pathway has been implicated in various cancers. Rilotumumab is an investigational, fully human monoclonal antibody that binds and neutralizes HGF. The purpose of this study was to evaluate the efficacy of rilotumumab in a U-87 MG mouse xenograft tumor model using 18 F-FDG and 18 F-FLT PET.MethodsU-87 MG tumor-bearing nude mice received rilotumumab or control IgG2. In the dose response study, increasing doses of rilotumumab (10, 30, 100, 300, or 500 μg) were administered, and mice were evaluated with 18 F-FDG PET at baseline and 7 days post-treatment. In the time course study, 300 μg of rilotumumab twice per week was used for the treatment, and mice were evaluated over 7 days using 18 F-FDG and 18 F-FLT PET.ResultsIn the dose response study, rilotumumab at doses of 300 and 500 μg was similarly effective against tumor growth. Treatment with 300 and 500 μg rilotumumab inhibited 18 F-FDG accumulation with significant decreases of ? 37% and ? 40% in the percent injected dose per gram of tissue (%ID/g), respectively. In the time course study, treatment with 300 μg rilotumumab inhibited 18 F-FDG and 18 F-FLT accumulation with a maximum %ID/g of ? 41% and ? 64%, respectively. No apparent differences between the use of either tracer to evaluate rilotumumab efficacy were observed.ConclusionsRilotumumab inhibited 18 F-FDG and 18 F-FLT accumulation as early as 2 and 4 days after treatment, respectively, in a mouse tumor model. Further studies to evaluate 18 F-FDG PET imaging as an early tumor response marker for rilotumumab are warranted. Rilotumumab is currently being tested in patients with MET-positive, advanced gastric and gastroesophageal cancer. |
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