title: [18F]FLT PET for non-invasive monitoring of early response to gene therapy in experimental gliomas.
abstract: The purpose of this study was to investigate the potential of 3'-deoxy-3'-[¹⁸F]fluorothymidine ([¹⁸F]FLT) positron emission tomography (PET) to detect early treatment responses in gliomas. Human glioma cells were stably transduced with genes yielding therapeutic activity, sorted for different levels of exogenous gene expression, and implanted subcutaneously into nude mice. Multimodality imaging during prodrug therapy included (a) magnetic resonance imaging, (b) PET with 9-(4-[¹⁸F]fluoro-3-hydroxymethylbutyl)guanine assessing exogenous gene expression, and (c) repeat [¹⁸F]FLT PET assessing antiproliferative therapeutic response. All stably transduced gliomas responded to therapy with significant reduction in tumor volume and [¹⁸F]FLT accumulation within 3 days after initiation of therapy. The change in [¹⁸F]FLT uptake before and after treatment correlated to volumetrically calculated growth rates. Therapeutic efficacy as monitored by [¹⁸F]FLT PET correlated to levels of therapeutic gene expression measured in vivo. Thus, [¹⁸F]FLT PET assesses early antiproliferative effects, making it a promising radiotracer for the development of novel treatments for glioma.
authors.affiliation: Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.|Center for Molecular Medicine (CMMC), Cologne, Germany.|Departments of Neurology, University Hospital Cologne, Cologne, Germany.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rueger
authors.affiliation: Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.|Departments of Neurology, University Hospital Cologne, Cologne, Germany.
authors.forename: Mitra
authors.initials: M
authors.lastname: Ameli
authors.affiliation: Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Li
authors.affiliation: Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.|Center for Molecular Medicine (CMMC), Cologne, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Winkeler
authors.affiliation: Department of Radiology, University Hospital Cologne, Cologne, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Rueckriem
authors.affiliation: Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vollmar
authors.affiliation: Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Galldiks
authors.affiliation: Department of Radiology, University Hospital Cologne, Cologne, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Hesselmann
authors.affiliation: Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.
authors.forename: Cornel
authors.initials: C
authors.lastname: Fraefel
authors.affiliation: Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Wienhard
authors.affiliation: Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Heiss
authors.affiliation: Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany. Andreas.Jacobs@nf.mpg.de.|Center for Molecular Medicine (CMMC), Cologne, Germany. Andreas.Jacobs@nf.mpg.de.|European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany. Andreas.Jacobs@nf.mpg.de.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015224:Dideoxynucleosides; D015870:Gene Expression; D015316:Genetic Therapy; D005910:Glioma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D013997:Time Factors; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D015224:Dideoxynucleosides; D049452:Green Fluorescent Proteins; C002854:alovudine