[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′-[ 18 F]fluorothymidine ([ 18 F]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 le...

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Published in:Molecular imaging and biology 2011-06, Vol.13 (3), p.547-557
Main Authors: Rueger, Maria A., Ameli, Mitra, Li, Hongfeng, Winkeler, Alexandra, Rueckriem, Benedikt, Vollmar, Stefan, Galldiks, Norbert, Hesselmann, Volker, Fraefel, Cornel, Wienhard, Klaus, Heiss, Wolf-Dieter, Jacobs, Andreas H.
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Cell Proliferation
Dideoxynucleosides
Gene Expression
Genetic Therapy
Glioma - diagnostic imaging
Glioma - pathology
Glioma - therapy
Green Fluorescent Proteins - metabolism
Humans
Imaging
Medicine
Medicine & Public Health
Mice
Mice, Nude
Positron-Emission Tomography
Radiology
Research Article
Time Factors
Treatment Outcome
Xenograft Model Antitumor Assays
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Summary:The purpose of this study was to investigate the potential of 3′-deoxy-3′-[ 18 F]fluorothymidine ([ 18 F]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-[ 18 F]fluoro-3-hydroxymethylbutyl)guanine assessing exogenous gene expression, and (c) repeat [ 18 F]FLT PET assessing antiproliferative therapeutic response. All stably transduced gliomas responded to therapy with significant reduction in tumor volume and [ 18 F]FLT accumulation within 3 days after initiation of therapy. The change in [ 18 F]FLT uptake before and after treatment correlated to volumetrically calculated growth rates. Therapeutic efficacy as monitored by [ 18 F]FLT PET correlated to levels of therapeutic gene expression measured in vivo . Thus, [ 18 F]FLT PET assesses early antiproliferative effects, making it a promising radiotracer for the development of novel treatments for glioma.
ISSN:1536-1632
1860-2002
DOI:10.1007/s11307-010-0361-6