[18F]FLT PET for non-invasive monitoring of early response to gene therapy in experimental gliomas.
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.
Rueger
Maria A
MA
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.
Ameli
Mitra
M
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.
Li
Hongfeng
H
Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.
Winkeler
Alexandra
A
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.
Rueckriem
Benedikt
B
Department of Radiology, University Hospital Cologne, Cologne, Germany.
Vollmar
Stefan
S
Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.
Galldiks
Norbert
N
Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.
Hesselmann
Volker
V
Department of Radiology, University Hospital Cologne, Cologne, Germany.
Fraefel
Cornel
C
Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.
Wienhard
Klaus
K
Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.
Heiss
Wolf-Dieter
WD
Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany.
Jacobs
Andreas H
AH
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.
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
D015224:Dideoxynucleosides; D049452:Green Fluorescent Proteins; C002854:alovudine