The ghrelin receptor (GHSR) is known to regulate various physiological processes including appetite, food intake, and growth hormone release. Its expression is mainly observed in the brain, pancreas, stomach, and intestine. However, the functions of the receptor have not been fully elucidated. GHSR imaging with positron emission tomography (PET) is expected to further understanding of the functions and pathologies of the receptor. In this study, we newly designed and synthesized diaminopyrimidine derivatives ([F]BPP-1 and [F]BPP-2) and evaluated their utility as novel PET probes targeting GHSR. In competitive binding assays, the binding affinity of BPP-2 for GHSR ( = 274 nM) was comparable to that of the diaminopyimidine lead compound Abb8a ( = 109 nM). In a biodistribution study using normal mice, [F]BPP-2 displayed low uptake in the brain and moderate uptake in the pancreas, but high radioactivity accumulation in bone was observed due to its defluorination . Taken together, although further improvement of the pharmacokinetics is needed, the diaminopyrimidine scaffold has potential for the development of useful GHSR-targeting PET probes.

中文翻译：

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用于检测大脑中生长素释放肽受体的新型 18F 标记 2,4-二氨基嘧啶衍生物的合成和生物学评价

众所周知，生长素释放肽受体 (GHSR) 可以调节各种生理过程，包括食欲、食物摄入和生长激素释放。其表达主要在脑、胰腺、胃和肠中观察到。然而，受体的功能尚未完全阐明。正电子发射断层扫描 (PET) 的 GHSR 成像有望进一步了解受体的功能和病理学。在本研究中，我们新设计并合成了二氨基嘧啶衍生物（[F]BPP-1 和 [F]BPP-2），并评估了它们作为针对 GHSR 的新型 PET 探针的实用性。在竞争性结合测定中，BPP-2 对 GHSR 的结合亲和力 (= 274 nM) 与二氨基嘧啶先导化合物 Abb8a (= 109 nM) 相当。在使用正常小鼠的生物分布研究中，[F]BPP-2 在大脑中表现出低摄取，在胰腺中表现出中等摄取，但由于其脱氟而在骨骼中观察到高放射性积累。总而言之，尽管需要进一步改进药代动力学，但二氨基嘧啶支架具有开发有用的 GHSR 靶向 PET 探针的潜力。