H. Manning
Faculty Member
Last active: 3/22/2018

3'-Deoxy-3'-[18F]-Fluorothymidine PET imaging reflects PI3K-mTOR-mediated pro-survival response to targeted therapy in colorectal cancer.

McKinley ET, Zhao P, Coffey RJ, Washington MK, Manning HC
PLoS One. 2014 9 (9): e108193

PMID: 25247710 · PMCID: PMC4172755 · DOI:10.1371/journal.pone.0108193

Biomarkers that predict response to targeted therapy in oncology are an essential component of personalized medicine. In preclinical treatment response studies that featured models of wild-type KRAS or mutant BRAF colorectal cancer treated with either cetuximab or vemurafenib, respectively, we illustrate that [(18)F]-FLT PET, a non-invasive molecular imaging readout of thymidine salvage, closely reflects pro-survival responses to targeted therapy that are mediated by PI3K-mTOR activity. Activation of pro-survival mechanisms forms the basis of numerous modes of resistance. Therefore, we conclude that [(18)F]-FLT PET may serve a novel and potentially critical role to predict tumors that exhibit molecular features that tend to reflect recalcitrance to MAPK-targeted therapy. Though these studies focused on colorectal cancer, we envision that the results may be applicable to other solid tumors as well.

MeSH Terms (10)

Animals Antineoplastic Agents Cell Line, Tumor Cetuximab Colorectal Neoplasms Mice Mice, Nude Phosphatidylinositol 3-Kinases Positron-Emission Tomography TOR Serine-Threonine Kinases

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