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.
Mol Imaging Biol. 2011 Jun;13(3):547-557. doi: 10.1007/s11307-010-0361-6.
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.
本研究旨在探讨 3'-去氧-3'-[¹⁸F]氟代胸苷([¹⁸F]FLT)正电子发射断层扫描(PET)在检测胶质瘤早期治疗反应中的潜力。人胶质瘤细胞被稳定转染产生治疗活性的基因,按不同水平的外源基因表达进行分选,并皮下植入裸鼠。在前药治疗期间进行的多模态成像包括:(a)磁共振成像,(b)评估外源基因表达的 9-(4-[¹⁸F]氟-3-羟甲基丁基)鸟嘌呤 PET,以及 (c)重复 [¹⁸F]FLT PET 评估抗增殖治疗反应。所有稳定转染的胶质瘤在治疗开始后 3 天内对治疗有反应,肿瘤体积和 [¹⁸F]FLT 积聚显著减少。治疗前后 [¹⁸F]FLT 摄取的变化与体积计算的生长率相关。通过 [¹⁸F]FLT PET 监测的治疗效果与体内测量的治疗基因表达水平相关。因此,[¹⁸F]FLT PET 评估早期抗增殖作用,使其成为开发新型胶质瘤治疗方法的有前途的示踪剂。