(2S,4S)-4-[18F]FEBGln 作为正电子发射断层扫描示踪剂用于肿瘤成像的评价,Molecular Pharmaceutics

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(2S,4S)-4-[18F]FEBGln 作为正电子发射断层扫描示踪剂用于肿瘤成像的评价
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2023-08-30 , DOI: 10.1021/acs.molpharmaceut.3c00544
Yong Huang ₁ , Yajing Liu ₂ , Chengze Li ₁ , Zhongjing Li ₁ , Hualong Chen ₃ , Lu Zhang ₃ , Ying Liang ₁ , Zehui Wu ₃

Affiliation

谷氨酰胺代谢相关示踪剂有可能使许多肿瘤可视化，因为谷氨酰胺是肿瘤的第二大能量来源。(2S,4S)-4-[ ¹⁸ F]FEBGln是通过在谷氨酰胺的碳-4上引入[ ^{18 F]氟乙氧基苄基而设计的。}本研究的目的是详细研究(2S,4S)-4-[ ^{18 F]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。}荷瘤MCF-7裸鼠的生物分布结果表明，(2S,4S)-4-[ ¹⁸ F]FEBGln具有较高的初始肿瘤摄取率和较快的清除率，导致肿瘤与肌肉的比率高达30注射后分钟。体内无明显脱氟作用。^{(2S,4S)-4-[ 18} F]FEBGln原位MCF-7荷瘤裸鼠的显微PET-CT成像结果与生物学分布结果一致。与(2S,4R)-4-[ ¹⁸ F]FGln相比，(2S,4S)-4-[ ¹⁸ F]FEBGln肿瘤保留较差，但在正常组织中清除也较快，因此具有更好的PET图像对比前者。与MCF-7荷载裸鼠中较差的保留不同，(2S,4S)-4-[ ¹⁸ F]FEBGln在NCI-h1975和22Rv1肿瘤模型中具有良好的保留。由于(2S,4S)-4-[ ¹⁸ F]FEBGln在正常肺中的摄取量较低，而在膀胱中的摄取量较高，因此有望用于肺癌的准确诊断，但不能准确判断前列腺癌。与放射性标记氨基酸在脑肿瘤应用中的优势一致，(2S,4S)-4-[ ^{18 F]FEBGln 能够以比[}¹⁸ F]FET 和 [ ¹⁸ F]FDG更高的对比度准确诊断 U87MG 胶质瘤，并且有是(2S,4S)-4-[ ¹⁸ F]FEBGln摄取与肿瘤生长周期之间的相关性。进一步的动力学模型分析表明(2S,4S)-4-[ ^{18 F]FEBGln与(2S,4R)-4-[}¹⁸ F]FGln相似，符合一室模型和Logan图模型，且预计可以评估肿瘤谷氨酰胺池的大小。因此，(2S,4S)-4-[ ¹⁸ F]FEBGln有望为胶质瘤、肺癌、乳腺癌的诊断、制定个性化方案、疗效评价提供强有力的影像学依据。

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Evaluation of (2S,4S)-4-[18F]FEBGln as a Positron Emission Tomography Tracer for Tumor Imaging

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.

更新日期：2023-08-30

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