Synthesis, Radiolabeling, and Biological Evaluation of (R)- and (S)-2-Amino-5-[18F]fluoro-2-methylpentanoic Acid ((R)-, (S)-[18F]FAMPe) as Potential Positron Emission Tomography Tracers for Brain Tumors,Journal of Medicinal Chemistry

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Synthesis, Radiolabeling, and Biological Evaluation of (R)- and (S)-2-Amino-5-[18F]fluoro-2-methylpentanoic Acid ((R)-, (S)-[18F]FAMPe) as Potential Positron Emission Tomography Tracers for Brain Tumors
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2015-05-04 00:00:00 , DOI: 10.1021/jm502023y
Ahlem Bouhlel ₁ , Dong Zhou ₁ , Aixiao Li ₁ , Liya Yuan ₁ , Keith M. Rich ₁ , Jonathan McConathy ₁

Affiliation

A novel ¹⁸F-labeled α,α-disubstituted amino acid-based tracer, 2-amino-5-[¹⁸F]fluoro-2-methylpentanoic acid ([¹⁸F]FAMPe), has been developed for brain tumor imaging with a longer alkyl side chain than previously reported compounds to increase brain availability via system L amino acid transport. Both enantiomers of [¹⁸F]FAMPe were obtained in good radiochemical yield (24–52% n = 8) and high radiochemical purity (>99%). In vitro uptake assays in mouse DBT gliomas cells revealed that (S)-[¹⁸F]FAMPe enters cells partly via sodium-independent system L transporters and also via other nonsystem A transport systems including transporters that recognize glutamine. Biodistribution and small animal PET/CT studies in the mouse DBT model of glioblastoma showed that both (R)- and (S)-[¹⁸F]FAMPe have good tumor imaging properties with the (S)-enantiomer providing higher tumor uptake and tumor to brain ratios. Comparison of the SUVs showed that (S)-[¹⁸F]FAMPe had higher tumor to brain ratios compared to (S)-[¹⁸F]FET, a well-established system L substrate.

中文翻译：

（R）-和（S）-2-氨基-5- [ ¹⁸ F]氟-2-甲基戊酸（（R）-，（S）-[ ¹⁸ F] FAMPe）的合成，放射性标记和生物学评价脑肿瘤的潜在正电子发射断层显像示踪剂。

一种新型的¹⁸ F标记的基于α，α-二取代氨基酸的示踪剂2-氨基-5- [ ¹⁸ F]氟-2-甲基戊酸（[ ¹⁸ F] FAMPe）已开发用于脑肿瘤成像。烷基侧链比以前报道的化合物更长，可通过系统L氨基酸转运增加大脑的利用率。[ ¹⁸ F] FAMPe的两种对映体均以良好的放射化学收率（24–52％n = 8）和较高的放射化学纯度（> 99％）获得。小鼠DBT胶质瘤细胞的体外摄取测定表明，（S）-[ ¹⁸F] FAMPe部分通过不依赖钠的系统L转运蛋白，也通过其他非系统A转运系统（包括识别谷氨酰胺的转运蛋白）进入细胞。胶质母细胞瘤小鼠DBT模型的生物分布和小动物PET / CT研究表明（R）-和（S）-[ ¹⁸ F] FAMPe均具有良好的肿瘤成像特性，而（S）-对映异构体可提供更高的肿瘤摄取和肿瘤与大脑的比例。SUV的比较表明（S）-[ ¹⁸ F] FAMPe与成熟的系统L底物（S）-[ ¹⁸ F] FET相比具有更高的瘤脑比例。

更新日期：2015-05-04

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