title: Molecular imaging of proliferation in vivo: positron emission tomography with [18F]fluorothymidine.
abstract: Deregulated cell cycle progression is a hallmark of cancer. Accordingly, a major part of therapeutic drugs has been designed to inhibit cell proliferation and tumor growth. Metabolic imaging with positron emission tomography (PET) and the glucose analog 2'-[(18)F]fluoro-2'-deoxyglucose (FDG) has been demonstrated to sensitively detect malignant tumors and to identify responding tumors early in the course of anticancer treatment. However, tumoral uptake of FDG reflects proliferation only in part and is associated with false positive findings due to unspecific tracer retention in inflammatory processes. Most recent advances in cancer treatment have come from the development of disease specific, molecular agents, many of which induce cell cycle arrest (cytostatic effect) instead of tumor cell death (cytotoxic effect). Thus, evaluating alterations in DNA metabolism may reflect response to treatment better than alterations in glucose utilization. PET with the thymidine analog 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) enables non-invasive imaging and quantification of the proliferation fraction of tumors. Furthermore, FLT has been suggested as surrogate marker for assessment of response to treatment, especially when targeted drugs are utilized. This article reports on metabolic pathways of radionucleosides in proliferating cells. Methods for in vivo assessment of the proliferative activity in preclinical and clinical studies are described with a focus on early monitoring response to therapy.
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, D-81675 Munich, Germany. andreas.buck@tum.de
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Buck
authors.forename: Ken
authors.initials: K
authors.lastname: Herrmann
authors.forename: Changxian
authors.initials: C
authors.lastname: Shen
authors.forename: Tobias
authors.initials: T
authors.lastname: Dechow
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester