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[18F]FLT PET for Non-Invasive Monitoring of Early Response to Gene Therapy in Experimental Gliomas

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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.

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Acknowledgments

This work is supported in part by the Deutsche Forschungsgemeinschaft (DFG-Ja98/1-2), Center for Molecular Medicine Cologne (CMMC-TV46), and 6th FW EU grant EMIL (LSHC-CT-2004-503569).

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Authors and Affiliations

  1. Laboratory for Gene Therapy and Molecular Imaging, Max Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931, Cologne, Germany

    Maria A. Rueger, Mitra Ameli, Hongfeng Li, Alexandra Winkeler, Stefan Vollmar, Norbert Galldiks, Cornel Fraefel, Klaus Wienhard, Wolf-Dieter Heiss & Andreas H. Jacobs

  2. Center for Molecular Medicine (CMMC), Cologne, Germany

    Maria A. Rueger, Alexandra Winkeler & Andreas H. Jacobs

  3. Departments of Neurology, University Hospital Cologne, Cologne, Germany

    Maria A. Rueger & Mitra Ameli

  4. Department of Radiology, University Hospital Cologne, Cologne, Germany

    Benedikt Rueckriem & Volker Hesselmann

  5. European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany

    Andreas H. Jacobs

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  1. Maria A. Rueger
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Correspondence to Andreas H. Jacobs.

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Rueger, M.A., Ameli, M., Li, H. et al. [18F]FLT PET for Non-Invasive Monitoring of Early Response to Gene Therapy in Experimental Gliomas. Mol Imaging Biol 13, 547–557 (2011). https://doi.org/10.1007/s11307-010-0361-6

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  • DOI: https://doi.org/10.1007/s11307-010-0361-6

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