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


Rueger, M A; Ameli, M; Li, H; Winkeler, A; Rueckriem, B; Vollmar, S; Galldiks, N; Hesselmann, V; Fraefel, C; Wienhard, K; Heiss, W D; Jacobs, A H (2011). [18F]FLT PET for Non-Invasive Monitoring of Early Response to Gene Therapy in Experimental Gliomas. Molecular Imaging and Biology, 13(3):547-557.

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. Key words: [18F]FLT PET, Glioma, Suicide gene therapy, HSV-1-tk

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. Key words: [18F]FLT PET, Glioma, Suicide gene therapy, HSV-1-tk

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Virology
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2011
Deposited On:15 Jul 2010 06:27
Last Modified:05 Apr 2016 14:11
Publisher:Springer
ISSN:1536-1632
Publisher DOI:https://doi.org/10.1007/s11307-010-0361-6
PubMed ID:20563754

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