The purpose of this study was to evaluate the tumor targeting and imaging properties of novel ¹¹¹In-labeled gonadotropin-releasing hormone (GnRH) peptides for human prostate cancer. Three new 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-linker-d-Phe-(d-Lys⁶-GnRH) peptides with different hydrocarbon linkers were designed to evaluate their effects on GnRH receptor binding affinities. The Aoc (aminooctanoic acid) linker was better than βAla (3-aminopropanoic acid) and Aun (aminoundecanoic acid) linkers in retaining strong receptor binding affinity. DOTA-Aoc-d-Phe-(d-Lys⁶-GnRH) exhibited 6.6 ± 0.1 nM GnRH receptor binding affinity. ¹¹¹In-DOTA-Aoc-d-Phe-(d-Lys⁶-GnRH) exhibited fast tumor uptake and urinary clearance in DU145 human prostate cancer-xenografted nude mice. The DU145 tumor lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using ¹¹¹In-DOTA-Aoc-d-Phe-(d-Lys⁶-GnRH) as an imaging probe, providing an insight into the design of new GnRH peptides for prostate cancer in the future.

本研究的目的是评估新型¹¹¹ In 标记促性腺激素释放激素 (GnRH) 肽对人类前列腺癌的肿瘤靶向和成像特性。设计了三种具有不同烃连接体的新 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸 (DOTA)-连接体-d- Phe-( d -Lys ⁶ -GnRH) 肽来评估其对 GnRH 受体结合亲和力的影响。 Aoc（氨基辛酸）接头在保留强受体结合亲和力方面优于βAla（3-氨基丙酸）和Aun（氨基十一烷酸）接头。 DOTA-Aoc- d -Phe-( d- Lys ⁶ -GnRH) 表现出 6.6 ± 0.1 nM GnRH 受体结合亲和力。 ¹¹¹ In-DOTA-Aoc- d -Phe-( d- Lys ⁶ -GnRH) 在 DU145 人前列腺癌异种移植裸鼠中表现出快速的肿瘤摄取和尿清除。使用¹¹¹ In-DOTA-Aoc- d -Phe-( d- Lys ⁶ -GnRH) 作为成像探针，通过单光子发射计算机断层扫描 (SPECT)/CT 可以清楚地显示 DU145 肿瘤病变，从而提供对设计的深入了解未来治疗前列腺癌的新 GnRH 肽。