title: Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review.
abstract: The positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been proposed to measure cell proliferation non-invasivelyin vivo. Hence, it should provide valuable information for response assessment to tumor therapies. To date, [18F]FLT uptake has found limited use as a response biomarker in clinical trials in part because a better understanding is needed of the determinants of [18F]FLT uptake and therapy-induced changes of its retention in the tumor. In this systematic review of preclinical [18F]FLT studies, comprising 174 reports, we identify the factors governing [18F]FLT uptake in tumors, among which thymidine kinase 1 plays a primary role. The majority of publications (83 %) report that decreased [18F]FLT uptake reflects the effects of anticancer therapies. 144 times [18F]FLT uptake was related to changes in proliferation as determined byex vivoanalyses. Of these approaches, 77 % describe a positive relation, implying a good concordance of tracer accumulation and tumor biology. These preclinical data indicate that [18F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies. Understanding of the parameters which influence cellular [18F]FLT uptake and retention as well as the mechanism of changes induced by therapy is essential for successful implementation of this PET tracer. Hence, our systematic review provides the background for the use of [18F]FLT in future clinical studies.
authors.affiliation: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-Universität (WWU) Münster, Münster, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Schelhaas
authors.affiliation: Comprehensive Cancer Imaging Centre, Imperial College London, UK.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Heinzmann
authors.affiliation: European Organization for Research and Treatment of Cancer Headquarters, Brussels, Belgium.
authors.forename: Vikram R
authors.initials: VR
authors.lastname: Bollineni
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Gerbrand M
authors.initials: GM
authors.lastname: Kramer
authors.affiliation: European Organization for Research and Treatment of Cancer Headquarters, Brussels, Belgium.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Imaging Sciences, University of Manchester, Manchester, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Waterton
authors.affiliation: Comprehensive Cancer Imaging Centre, Imperial College London, UK.
authors.forename: Eric O
authors.initials: EO
authors.lastname: Aboagye
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Shields
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, UK.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Soloviev
authors.affiliation: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-Universität (WWU) Münster, Münster, Germany.; Department of Geriatric Medicine, Johanniter Hospital, Bonn, Germany.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D015224:Dideoxynucleosides / Q000008:administration & dosage*; D004353:Drug Evaluation, Preclinical; D016903:Drug Monitoring / Q000379:methods*; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy*; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*
chemical_list: D015224:Dideoxynucleosides; C002854:alovudine
keywords: FLT; Oncology.; positron emission tomography