评估(2S,4S)-4-[18F]FEBGln作为肿瘤成像的正电子发射断层扫描示踪剂。
Evaluation of (2S,4S)-4-[18F]FEBGln as a Positron Emission Tomography Tracer for Tumor Imaging.
发表日期:2023 Aug 30
作者:
Yong Huang, Yajing Liu, Chengze Li, Zhongjing Li, Hualong Chen, Lu Zhang, Ying Liang, Zehui Wu
来源:
Brain Structure & Function
摘要:
由于谷氨酰胺是肿瘤的第二大能源来源,与谷氨酰胺代谢相关的示踪剂具有可视化众多肿瘤的潜力。(2S,4S)-4-[18F]FEBGln在谷氨酰胺的碳-4位引入了[18F]氟乙氧基苄基。本研究的目的是详细研究(2S,4S)-4-[18F]FEBGln的药代动力学特性和肿瘤正电子发射断层扫描(PET)成像特征。裸鼠MCF-7肿瘤的生物分布结果显示,(2S,4S)-4-[18F]FEBGln具有高的初期肿瘤摄取率和快速的清除率,在注射后30分钟时呈现较高的肿瘤-肌肉比。体内没有明显的脱氟现象。原位移植MCF-7肿瘤的裸鼠的微型PET-CT成像结果与生物分布结果一致。与(2S,4R)-4-[18F]FGln相比,(2S,4S)-4-[18F]FEBGln表现出较差的肿瘤保留性,但其在正常组织的清除也很快,因此具有比前者更好的PET图像对比度。与MCF-7移植裸鼠中的病灶保留性差不同,(2S,4S)-4-[18F]FEBGln在NCI-h1975和22Rv1肿瘤模型中保留性良好。由于(2S,4S)-4-[18F]FEBGln在正常肺组织中的摄取较低,在膀胱中的摄取较高,预期可用于准确诊断肺癌,但不能准确定位前列腺癌。与放射性标记的氨基酸在脑肿瘤应用中具有的优势一致,(2S,4S)-4-[18F]FEBGln与[18F]FET和[18F]FDG相比,能更准确地诊断U87MG胶质瘤,并且(2S,4S)-4-[18F]FEBGln的摄取与肿瘤生长周期相关。进一步的动力学模型分析显示,(2S,4S)-4-[18F]FEBGln与(2S,4R)-4-[18F]FGln相似,符合一室模型和Logan图形模型,有望评估肿瘤的谷氨酰胺库容量。因此,(2S,4S)-4-[18F]FEBGln有望为胶质瘤、肺癌和乳腺癌的诊断、个体化治疗方案制定和疗效评估提供强有力的成像依据。
Glutamine metabolism-related tracers have the potential to visualize numerous tumors because glutamine is the second largest source of energy for tumors. (2S,4S)-4-[18F]FEBGln was designed by introducing [18F]fluoroethoxy benzyl on carbon-4 of glutamine. The aim of this study was to investigate the pharmacokinetic properties and tumor positron emission tomography (PET) imaging characteristics of (2S,4S)-4-[18F]FEBGln in detail. The biodistribution results of nude mice bearing MCF-7 tumor showed that (2S,4S)-4-[18F]FEBGln had high initial tumor uptake, and a fast clearance rate, resulting in a high tumor-to-muscle ratio at 30 min postinjection. There was no obvious defluorination in vivo. The micro-PET-CT imaging results of (2S,4S)-4-[18F]FEBGln orthotopic MCF-7 tumor-bearing nude mice were consistent with the biological distribution results. Compared with (2S,4R)-4-[18F]FGln, (2S,4S)-4-[18F]FEBGln showed poor tumor retention, but its clearance in normal tissues was also fast, so it had better PET image contrast than the former. Unlike poor retention in MCF-7-bearing nude mice, (2S,4S)-4-[18F]FEBGln has good retention in NCI-h1975 and 22Rv1 tumor models. Since (2S,4S)-4-[18F]FEBGln has low uptake in normal lungs and high uptake in the bladder, it is expected to be used in the accurate diagnosis of lung cancer but cannot accurately determine prostate cancer. Consistent with the advantages of radiolabeled amino acids in the application of brain tumors, (2S,4S)-4-[18F]FEBGln accurately diagnoses U87MG glioma with higher contrast than [18F]FET and [18F]FDG, and there is a correlation between (2S,4S)-4-[18F]FEBGln uptake and tumor growth cycle. Further kinetic model analysis showed that (2S,4S)-4-[18F]FEBGln was similar to (2S,4R)-4-[18F]FGln, conforming to the one-compartment model and the Logan graphical model, and was expected to assess the size of the glutamine pool of the tumor. Therefore, (2S,4S)-4-[18F]FEBGln is expected to provide a strong imaging basis for the diagnosis, formulation of personalized plans, and efficacy evaluation of glioma, lung cancer, and breast cancer.