FDG-PET as a pharmacodynamic biomarker for early assessment of treatment response to linifanib (ABT-869) in a non-small cell lung cancer xenograft model.

Abstract

Linifanib (ABT-869) is a multitargeted receptor tyrosine kinase inhibitor. This work aims to evaluate F-fluorodeoxyglucose-positron emission tomography (FDG-PET) as a pharmacodynamic (PD) biomarker for linifanib treatment utilizing the Calu-6 model of human non-small cell lung (NSCLC) cancer in SCID-beige mice. Animals received either vehicle or 12.5 mg/kg linifanib orally twice a day for the duration of the study. Imaging was performed at -1, 1, 3, and 7 days after beginning treatment (n = 12-14 per group). Linifanib inhibited tumor growth and suppressed tumor metabolic activity. Changes in tumor FDG uptake were observed as early as 1 day after beginning linifanib treatment and were sustained for the duration of the study. This study confirms that linifanib is efficacious in this xenograft model of human NSCLC and confirms FDG-PET is a potential PD biomarker strategy for linifanib therapy.

• Authors: Sarah R Mudd, Martin J Voorbach, David R Reuter, Paul Tapang, Jonathan A Hickson, Marion Refici-Buhr, Gerard B Fox, Daniel H Albert, Yanping Luo, Mark Day
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 69 Issue 6 Pg. 1669-72 (Jun 2012) ISSN: 1432-0843 [Electronic] Germany
• PMID: 22327787 (Publication Type: Journal Article)

Chemical References

• Indazoles
• Phenylurea Compounds
• Fluorodeoxyglucose F18
• linifanib
• Receptor Protein-Tyrosine Kinases

Topics

• Animals
• Carcinoma, Non-Small-Cell Lung (diagnostic imaging, drug therapy)
• Cell Line, Tumor
• Fluorodeoxyglucose F18
• Humans
• Indazoles (therapeutic use)
• Lung Neoplasms (diagnostic imaging, drug therapy)
• Mice
• Mice, SCID
• Phenylurea Compounds (therapeutic use)
• Positron-Emission Tomography
• Receptor Protein-Tyrosine Kinases (antagonists & inhibitors)
• Xenograft Model Antitumor Assays