The ghrelin receptor, also known as the growth hormone secretagogue receptor 1a (GHS-R1a), is a G-protein-coupled receptor that is differentially expressed in healthy tissue and several cancers, including prostate, testicular, and ovarian. Selectively targeting the ghrelin receptor using fluorine-18 tagged entities would allow localization and visualization of ghrelin receptor expressing carcinomas using PET imaging. The endogenous ligand ghrelin, a 28 amino acid peptide with 3.1 nM affinity, has poor in vivo stability. Here we report on ghrelin(1–8) analogues bearing modifications at residues 1, 3, 4, and 8. The lead analogue, [Inp¹,Dpr³(6-fluoro-2-naphthoate),1-Nal⁴,Thr⁸]ghrelin(1–8), possessed an IC₅₀ value of 0.11 nM that is a 28-fold improvement compared to the natural ligand. A novel 6-fluoro-2-pentafluorophenyl naphthoate (PFPN) prosthetic group was synthesized to incorporate fluorine-18 for PET imaging. This is not only the highest affinity ghrelin analogue reported but also the shortest ghrelin analogue capable of binding GHS-R1a with better affinity than ghrelin(1–28).

中文翻译：

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Ghrelin（1–8）的结构-活性研究导致Ghrelin受体的高亲和力含氟配体

ghrelin受体，也称为生长激素促分泌素受体1a（GHS-R1a），是一种G蛋白偶联受体，在健康组织和几种癌症（包括前列腺癌，睾丸癌和卵巢癌）中差异表达。使用氟18标签的实体选择性靶向生长素释放肽受体，将允许使用PET成像对生长激素释放肽受体表达的癌进行定位和可视化。内源性配体生长素释放肽是具有3.1 nM亲和力的28个氨基酸的肽，其体内稳定性较差。在这里，我们报道了在残基1、3、4和8处带有修饰的ghrelin（1-8）类似物。主要类似物[Inp ¹，Dpr ³（6-fluoro-2-naphthoate），1-Nal ⁴，Thr ⁸ ] ghrelin（1–8），IC ₅₀值为0.11 nM，与天然配体相比提高了28倍。合成了新型的6-氟-2-五氟苯基萘甲酸（PFPN）辅基，将氟-18引入PET成像中。这不仅是报道的最高亲和力的生长素释放肽类似物，而且是最短的生长素释放肽类似物，能够以比生长素释放肽更好的亲和力结合GHS-R1a（1-28）。