Radiolabeled bombesin (BBN) analogs have long been used for developing gastrin-releasing peptide receptor (GRPR) targeted imaging probes, and tracers with excellent in vivo performance including high tumor uptake, high contrast, and favorable pharmacokinetics are highly desired. In this study, we compared the 68Ga-labeled GRPR agonist (Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2, BBN7-14) and antagonist (d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, RM26) for the positron emission tomography (PET) imaging of prostate cancer. The in vitro stabilities, receptor binding, cell uptake, internalization, and efflux properties of the probes 68Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-Aca-BBN7-14 and 68Ga-NOTA-poly(ethylene glycol)3 (PEG3)-RM26 were studied in PC-3 cells, and the in vivo GRPR targeting abilities and kinetics were investigated using PC-3 tumor xenografted mice. BBN7-14, PEG3-RM26, NOTA-Aca-BBN7-14, and NOTA-PEG3-RM26 showed similar binding affinity to GRPR. In PC-3 tumor-bearing mice, the tumor uptake of 68Ga-NOTA-PEG3-RM26 remained at around 3.00 percentage of injected dose per gram of tissue within 1 h after injection, in contrast with 68Ga-NOTA-Aca-BBN7-14, which demonstrated rapid elimination and high background signal. Additionally, the majority of the 68Ga-NOTA-PEG3-RM26 remained intact in mouse serum at 5 min after injection, while almost all of the 68Ga-NOTA-Aca-BBN7-14 was degraded under the same conditions, demonstrating more-favorable in vivo pharmacokinetic properties and metabolic stabilities of the antagonist probe relative to its agonist counterpart. Overall, the antagonistic GRPR targeted probe 68Ga-NOTA-PEG3-RM26 is a more-promising candidate than the agonist 68Ga-NOTA-Aca-BBN7-14 for the PET imaging of prostate cancer patients.

中文翻译：

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带有Ga-68标签的胃泌素释放肽受体激动剂BBN7-14和拮抗剂RM26的前列腺癌正电子发射断层显像。

长期以来，放射性标记的蛙皮素（BBN）类似物一直用于开发胃泌素释放肽受体（GRPR）靶向成像探针，人们迫切需要具有出色的体内性能（包括高肿瘤摄取，高对比度和良好的药代动力学）的示踪剂。在这项研究中，我们比较了68Ga标记的GRPR激动剂（Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2，BBN7-14）和拮抗剂（d-Phe-Gln-Trp-Ala-Val- Gly-His-Sta-Leu-NH2，RM26）用于前列腺癌的正电子发射断层扫描（PET）成像。探针68Ga-1,4,7-三氮杂环壬烷-1,4,7-三乙酸（NOTA）-Aca-BBN7-14和68Ga-NOTA的体外稳定性，受体结合，细胞摄取，内在化和外排特性-聚（乙二醇）3（PEG3）-RM26在PC-3细胞中进行了研究，并使用PC-3肿瘤异种移植小鼠研究了体内GRPR靶向能力和动力学。BBN7-14，PEG3-RM26，NOTA-Aca-BBN7-14和NOTA-PEG3-RM26显示出与GRPR相似的结合亲和力。在PC-3荷瘤小鼠中，注射后1 h内，对68Ga-NOTA-PEG3-RM26的肿瘤吸收保持在每克组织注射剂量约3.00％的水平，而68Ga-NOTA-Aca-BBN7-14 ，显示出快速消除和高背景信号的能力。此外，大多数68Ga-NOTA-PEG3-RM26在注射后5分钟内在小鼠血清中保持完整，而几乎所有68Ga-NOTA-Aca-BBN7-14在相同条件下均被降解，表明在拮抗剂探针相对于其激动剂对应物的体内药代动力学性质和代谢稳定性。全面的，