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

被引：0
作者：
Maria A. Rueger
Mitra Ameli
Hongfeng Li
Alexandra Winkeler
Benedikt Rueckriem
Stefan Vollmar
Norbert Galldiks
Volker Hesselmann
Cornel Fraefel
Klaus Wienhard
Wolf-Dieter Heiss
Andreas H. Jacobs
机构：
[1] Max Planck-Institute for Neurological Research,Laboratory for Gene Therapy and Molecular Imaging
[2] Center for Molecular Medicine (CMMC),Departments of Neurology
[3] University Hospital Cologne,Department of Radiology
[4] University Hospital Cologne,European Institute for Molecular Imaging (EIMI)
[5] University of Münster,undefined
来源：
Molecular Imaging and Biology | 2011年 / 13卷
关键词：
[18F]FLT PET; Glioma; Suicide gene therapy; HSV-1-;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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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页码：547 / 557
页数：10
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  • [21] Von Der HM(2002)Basis of FLT as a cell proliferation marker: comparative uptake studies with [3H]thymidine and [3H]arabinothymidine, and cell-analysis in 22 asynchronously growing tumor cell lines Nucl Med Biol 29 281-287
  • [22] Halter G(2002)Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells J Nucl Med 43 1210-1217
  • [23] Glatting G(2003)Monitoring tumor cell proliferation by targeting DNA synthetic processes with thymidine and thymidine analogs J Nucl Med 44 2027-2032
  • [24] Cobben DC(1992)Comparisons of anti-human immunodeficiency virus activities, cellular transport, and plasma and intracellular pharmacokinetics of 3′-fluoro-3′-deoxythymidine and 3′-azido-3′-deoxythymidine Antimicrob Agents Chemother 36 808-818
  • [25] Jager PL(2007)Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study J Clin Oncol 25 4714-4721
  • [26] Elsinga PH(2002)Early changes in [18F]FLT uptake after chemotherapy: an experimental study Eur J Nucl Med Mol Imaging 29 1462-1469
  • [27] Maas B(2005)Early detection of tumor response to chemotherapy by 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography: the effect of cisplatin on a fibrosarcoma tumor model in vivo Cancer Res 65 4202-4210
  • [28] Suurmeijer AJ(2005)Monitoring antiproliferative responses to kinase inhibitor therapy in mice with 3′-deoxy-3′-18F-fluorothymidine PET J Nucl Med 46 114-120
  • [29] Hoekstra HJ(2000)A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme Hum Gene Ther 11 2389-2401
  • [30] Francis DL(1999)A phase 1-2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir. GLI328 European–Canadian Study Group Hum Gene Ther 10 2325-2335
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