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PLoS One. 2014 Sep 23;9(9):e108193. doi: 10.1371/journal.pone.0108193. eCollection 2014.

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

Author information

1
The Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical School, Nashville, TN, United States of America; Department of Biomedical Engineering, Vanderbilt University Medical School, Nashville, TN, United States of America; Department of Medicine, Vanderbilt University Medical School, Nashville, TN, United States of America.
2
The Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical School, Nashville, TN, United States of America.
3
Department of Medicine, Vanderbilt University Medical School, Nashville, TN, United States of America; Department of Vanderbilt Ingram Cancer Center, Vanderbilt University Medical School, Nashville, TN, United States of America.
4
Department of Medicine, Vanderbilt University Medical School, Nashville, TN, United States of America; Department of Vanderbilt Ingram Cancer Center, Vanderbilt University Medical School, Nashville, TN, United States of America; Department of Pathology, Vanderbilt University Medical School, Nashville, TN, United States of America.
5
The Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical School, Nashville, TN, United States of America; Department of Biomedical Engineering, Vanderbilt University Medical School, Nashville, TN, United States of America; Department of Vanderbilt Ingram Cancer Center, Vanderbilt University Medical School, Nashville, TN, United States of America; Department of Radiology and Radiological Sciences, Vanderbilt University Medical School, Nashville, TN, United States of America; Department of Neurosurgery, Vanderbilt University Medical School, Nashville, TN, United States of America; Department of Chemical and Physical Biology, Vanderbilt University Medical School, Nashville, TN, United States of America.

Abstract

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.

PMID:
25247710
PMCID:
PMC4172755
DOI:
10.1371/journal.pone.0108193
[Indexed for MEDLINE]
Free PMC Article

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