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.
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.
Advanced Technology Translational Sciences, Global Pharmaceutical R & D, Abbott Laboratories, Abbott Park, IL 60064, USA. sarah.mudd@abbott.com
Sarah R
SR
Mudd
Martin J
MJ
Voorbach
David R
DR
Reuter
Paul
P
Tapang
Jonathan A
JA
Hickson
Marion
M
Refici-Buhr
Gerard B
GB
Fox
Daniel H
DH
Albert
Yanping
Y
Luo
Mark
M
Day
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy*; D045744:Cell Line, Tumor; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007191:Indazoles / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
D007191:Indazoles; D010671:Phenylurea Compounds; D019788:Fluorodeoxyglucose F18; C513486:linifanib; D020794:Receptor Protein-Tyrosine Kinases