title: 3'-Deoxy-3'-[18F]-Fluorothymidine PET imaging reflects PI3K-mTOR-mediated pro-survival response to targeted therapy in colorectal cancer.
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.
authors.affiliation: 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.
authors.forename: Eliot T
authors.initials: ET
authors.lastname: McKinley
authors.affiliation: The Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical School, Nashville, TN, United States of America.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Coffey
authors.affiliation: 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.
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.affiliation: 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.
authors.forename: H Charles
authors.initials: HC
authors.lastname: Manning
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D049268:Positron-Emission Tomography; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D000068818:Cetuximab; D019869:Phosphatidylinositol 3-Kinases; D058570:TOR Serine-Threonine Kinases