Evaluation of the antitumor effects of rilotumumab by PET imaging in a U-87 MG mouse xenograft model.

Abstract

INTRODUCTION:

Dysregulation 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.

METHODS:

U-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.

RESULTS:

In 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.

CONCLUSIONS:

Rilotumumab 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.

• Authors: Karen Rex, Xiaoman Z Lewis, Sundaresan Gobalakrishnan, Charles Glaus, Matthew D Silva, Robert Radinsky, Teresa L Burgess, Sanjiv S Gambhir, Angela Coxon
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 40 Issue 4 Pg. 458-63 (May 2013) ISSN: 1872-9614 [Electronic] United States
• PMID: 23454250 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Biomarkers
• Dideoxynucleosides
• Fluorodeoxyglucose F18
• rilotumumab
• Hepatocyte Growth Factor
• alovudine

Topics

• Animals
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (pharmacology, therapeutic use)
• Biological Transport (drug effects)
• Biomarkers (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dideoxynucleosides
• Dose-Response Relationship, Drug
• Female
• Fluorodeoxyglucose F18 (metabolism)
• Glioblastoma (diagnostic imaging, drug therapy, metabolism, pathology)
• Hepatocyte Growth Factor (metabolism)
• Humans
• Mice
• Molecular Targeted Therapy
• Positron-Emission Tomography
• Time Factors
• Xenograft Model Antitumor Assays