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靶向GRPR的放射性蛙皮素药物在前列腺癌诊疗中的研究进展
宋浩辉
徐梦欣
马旭倩
蔡杰
何超
刘冰琳
苏琪
刘志博
作者及单位信息
·
DOI： 10.3760/cma.j.cn321828-20230310-00055
Research progress of radiolabeled bombesin drugs targeting GRPR in the diagnosis and treatment of prostate cancer
Song Haohui
Xu Mengxin
Ma Xuqian
Cai Jie
He Chao
Liu Binglin
Su Qi
Liu Zhibo
Authors Info & Affiliations
Song Haohui
Boomray Pharmaceuticals Co., Ltd, Suzhou 215011, China
Xu Mengxin
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
Ma Xuqian
Boomray Pharmaceuticals Co., Ltd, Suzhou 215011, China
Cai Jie
Boomray Pharmaceuticals Co., Ltd, Suzhou 215011, China
He Chao
Boomray Pharmaceuticals Co., Ltd, Suzhou 215011, China
Liu Binglin
Boomray Pharmaceuticals Co., Ltd, Suzhou 215011, China
Su Qi
Boomray Pharmaceuticals Co., Ltd, Suzhou 215011, China
Liu Zhibo
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
·
DOI： 10.3760/cma.j.cn321828-20230310-00055
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摘要

前列腺癌是男性中最常见的癌症，也是全球男性癌症相关死亡的第五大原因。胃泌素释放肽受体(GRPR)是前列腺特异膜抗原(PSMA)的重要补充靶点，也是前列腺癌诊疗的关键靶标。放射性核素标记的蛙皮素(BBN)类似物可准确靶向肿瘤细胞过表达的GRPR，对前列腺癌病变进行早期诊疗。该文着重讨论了 99Tc m、 111In、 68Ga、 64Cu、 18F和 177Lu等核素标记的用于诊断和肽受体放射性核素治疗的BBN类似物。

前列腺肿瘤;受体，铃蟾肽;前列腺特异膜抗原;发展趋势
ABSTRACT

Prostate cancer is the most common cancer among men and the fifth leading cause of cancer-related death among men worldwide. Gastrin-releasing peptide receptor (GRPR) is an important complementary target of prostate specific membrane antigen (PSMA) and a key target for prostate cancer diagnosis and treatment. Radionuclide labeled bombesin (BBN) analogues can accurately target overexpressed GRPR in tumor cells, thus providing early diagnosis and treatment of prostate cancer. In this review, we focus on the studies of 99Tc m, 111In, 68Ga, 64Cu, 18F, and 177Lu nuclide-labeled BBN analogues for diagnosis and peptide receptor radionuclide therapy.

Prostatic neoplasms;Receptors, bombesin;Prostate-specific membrane antigen;Trends
Liu Zhibo, Email: nc.defudabe.ukpuilbz
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宋浩辉,徐梦欣,马旭倩,等. 靶向GRPR的放射性蛙皮素药物在前列腺癌诊疗中的研究进展[J]. 中华核医学与分子影像杂志,2024,44(12)：764-768.

DOI:10.3760/cma.j.cn321828-20230310-00055

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前列腺癌是全球第三大常见的癌症，也是全球男性癌症死亡的第五大原因 [ 1 ]。前列腺特异膜抗原(prostate specific membrane antigen, PSMA)是目前研究最为广泛且被认为是前列腺癌诊疗最理想的靶点 [ 2 , 3 ]。但是该靶点存在一定局限性，例如对于早期、前列腺特异抗原(prostate specific antigen, PSA)低水平或早期复发前列腺癌的检出率较低 [ 4 ]。文献统计，大约5%的原发性前列腺癌和15%的转移性前列腺癌的PSMA检测结果为阴性 [ 5 ]。但是在这部分患者中发现，胃泌素释放肽受体(gastrin-releasing peptide receptor, GRPR)在病变部位呈高表达，在正常前列腺组织和良性前列腺增生中基本不表达 [ 6 , 7 ]。GRPR表达与Gleason评分呈一定水平的负相关性，即低Gleason评分下GRPR高表达，而高Gleason评分下GRPR低表达 [ 8 ]。因此，GRPR放射性配体是PSMA靶向诊疗前列腺癌的有效补充 [ 9 ]。
蛙皮素(bombesin, BBN)是意大利药理学家Vittorio Erspamer从欧洲青蛙(Bombina bombina和Bombina variegata)的皮肤中分离发现的一种十四肽。后来，在许多其他物种中也发现了BBN类似物，例如人体内的胃泌素释放肽(gastric-releasing peptide, GRP),其是哺乳动物体内的一种神经激素，常分布于外周神经系统和胃肠道神经纤维中。GRPR是一种G蛋白偶联受体，能够诱导癌细胞生长 [ 10 ]。近年来，GRPR被发现在前列腺癌、乳腺癌、肺癌和肾细胞癌等癌症中高表达。本文将重点讨论 99Tc m、 111In、 68Ga、 64Cu、 18F、 177Lu等核素标记的靶向GRPR的放射性BBN药物在前列腺癌诊疗中的研究进展，相关药物见 表1 。
类别 放射性核素 半衰期 主要药物 应用
诊断类 99Tc m 6.01 h 99Tc m-RP527 [ 11 ]、 99Tc m-Demobesin 4 [ 12 , 13 ]、 99Tc m-Demobesin 1 [ 14 ] SPECT
  111In 67.31 h 111In-NOTA-PEG2-RM26 [ 15 ]、 111In-NODAGA-PEG2-RM26 [ 15 ]、 111In-DOTA-PEG2-RM26 [ 15 ]、 111In-DOTAGA-PEG2-RM26 [ 15 ] SPECT
  68Ga 67.71 min 68Ga-SB3 [ 16 , 17 ]、 68Ga-RM2 [ 18 , 19 , 20 ]、 68Ga-RM26 [ 21 ]、 68Ga-ProBOMB1 [ 22 ]、 68Ga-ProBOMB2 [ 23 ] PET
  64Cu 12.7 h 64Cu-DOTA-Aoc-BBN(7-14) [ 24 ]、 64Cu-DOTA-Aca-BBN(7-14) [ 25 ]、 64Cu-DOTA-[Lys 3]BBN [ 25 ]、 64Cu-SAR-BBN [ 26 , 27 ] PET
  18F 109.7 min 18F-BAY86-4367 [ 28 , 29 , 30 ]、 18F-Al-NOTA-8-Aoc-BBN(7-14)NH 2 [ 31 ] PET
治疗类 177Lu 6.7 d 177Lu-AMBA [ 32 ]、 177Lu-RM2 [ 33 ]、 177Lu-AMTG [ 34 ]、 177Lu-AMTG2 [ 34 ]、 177Lu-ProBOMB1 [ 35 ]、 177Lu-ProBOMB2 [ 23 ] SPECT/PRRT
基于蛙皮素(BBN)的靶向GRPR放射性药物

注：DOTA为1，4，7，10-四氮杂环十二烷-1，4，7，10-四乙酸，DOTAGA为1，4，7，10-四氮杂环十二烷-1-戊二酸-4，7，10-三乙酸，GRPR为胃泌素释放肽受体，Lys为赖氨酸，NODAGA为1，4，7-三氮杂环壬烷-1-戊二酸-4，7-二乙酸，NOTA为1，4，7-三氮杂环壬烷-1，4，7-三乙酸，PEG为聚乙二醇，PRRT为肽受体放射性核素治疗

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备注信息
A
刘志博，Email: nc.defudabe.ukpuilbz
B

宋浩辉：研究实施、论文撰写；徐梦欣、马旭倩：论文修改；蔡杰、何超、刘冰琳、苏琪：统计学分析；刘志博：研究指导

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