PDF(Pubmed)
Abstract：
UNASSIGNED: Central to targeted radionuclide imaging and therapy of prostate cancer (PCa) are prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals. Gastrin-releasing peptide receptor (GRPR) targeting has been proposed as a potential additional approach for PCa theranostics. The aim of this study was to investigate to what extent and at what stage of the disease GRPR-targeting applications can complement PSMA-targeting theranostics in the management of PCa.
UNASSIGNED: Binding of the GRPR- and PSMA-targeting radiopharmaceuticals [177Lu]Lu-NeoB and [177Lu]Lu-PSMA-617, respectively, was evaluated and compared on tissue sections of 20 benign prostatic hyperplasia (BPH), 16 primary PCa and 17 progressive castration-resistant PCa (CRPC) fresh frozen tissue specimens. Hematoxylin-eosin and alpha-methylacyl-CoA racemase stains were performed to identify regions of prostatic adenocarcinoma and potentially high-grade prostatic intraepithelial neoplasia. For a subset of primary PCa samples, RNA in situ hybridization (ISH) was used to identify target mRNA expression in defined tumor regions.
UNASSIGNED: The highest median [177Lu]Lu-NeoB binding was observed in primary PCa samples, while median and overall [177Lu]Lu-PSMA-617 binding was highest in CRPC samples. The highest [177Lu]Lu-NeoB binding was observed in 3/17 CRPC samples of which one sample showed no [177Lu]Lu-PSMA-617 binding. RNA ISH analyses showed a trend between mRNA expression and radiopharmaceutical binding, and confirmed the distinct GRPR and PSMA expression patterns in primary PCa observed with radiopharmaceutical binding.
UNASSIGNED: Our study emphasizes that GRPR-targeting approaches can contribute to improved PCa management and complement currently applied PSMA-targeting strategies in both early and late stage PCa.
UNASSIGNED: Binding of the GRPR- and PSMA-targeting radiopharmaceuticals [177Lu]Lu-NeoB and [177Lu]Lu-PSMA-617, respectively, was evaluated and compared on tissue sections of 20 benign prostatic hyperplasia (BPH), 16 primary PCa and 17 progressive castration-resistant PCa (CRPC) fresh frozen tissue specimens. Hematoxylin-eosin and alpha-methylacyl-CoA racemase stains were performed to identify regions of prostatic adenocarcinoma and potentially high-grade prostatic intraepithelial neoplasia. For a subset of primary PCa samples, RNA in situ hybridization (ISH) was used to identify target mRNA expression in defined tumor regions.
UNASSIGNED: The highest median [177Lu]Lu-NeoB binding was observed in primary PCa samples, while median and overall [177Lu]Lu-PSMA-617 binding was highest in CRPC samples. The highest [177Lu]Lu-NeoB binding was observed in 3/17 CRPC samples of which one sample showed no [177Lu]Lu-PSMA-617 binding. RNA ISH analyses showed a trend between mRNA expression and radiopharmaceutical binding, and confirmed the distinct GRPR and PSMA expression patterns in primary PCa observed with radiopharmaceutical binding.
UNASSIGNED: Our study emphasizes that GRPR-targeting approaches can contribute to improved PCa management and complement currently applied PSMA-targeting strategies in both early and late stage PCa.
摘要：
■前列腺癌（PCa）的靶向放射性核素成像和治疗的核心是前列腺特异性膜抗原（PSMA）靶向放射性药物。胃泌素释放肽受体（GRPR）靶向已被提出作为PCa疗法的潜在附加方法。这项研究的目的是调查GRPR靶向应用在何种程度上以及在疾病的哪个阶段可以在PCa的管理中补充PSMA靶向疗法。
■针对GRPR和PSMA的放射性药物[177Lu]Lu-NeoB和[177Lu]Lu-PSMA-617的结合，在20例良性前列腺增生（BPH）的组织切片上进行了评估和比较，16个原发性PCa和17个进行性去势抗性PCa(CRPC)新鲜冷冻组织标本。进行苏木精-伊红和α-甲基酰基-CoA消旋酶染色以识别前列腺腺癌和潜在的高级别前列腺上皮内瘤变的区域。对于主PCa样本的子集，RNA原位杂交(ISH)用于鉴定确定的肿瘤区域中的靶mRNA表达。
■在原发性PCa样品中观察到最高的中值[177Lu]Lu-NeoB结合，而[177Lu]Lu-PSMA-617的中位数和总体结合在CRPC样品中最高。在3/17个CRPC样品中观察到最高的[177Lu]Lu-NeoB结合,其中一个样品没有显示[177Lu]Lu-PSMA-617结合。RNAISH分析显示mRNA表达和放射性药物结合之间的趋势，并证实了在放射性药物结合下观察到的原发性PCa中不同的GRPR和PSMA表达模式。
■我们的研究强调，GRPR靶向方法可以有助于改善PCa管理，并补充目前在早期和晚期PCa中应用的PSMA靶向策略。
■针对GRPR和PSMA的放射性药物[177Lu]Lu-NeoB和[177Lu]Lu-PSMA-617的结合，在20例良性前列腺增生（BPH）的组织切片上进行了评估和比较，16个原发性PCa和17个进行性去势抗性PCa(CRPC)新鲜冷冻组织标本。进行苏木精-伊红和α-甲基酰基-CoA消旋酶染色以识别前列腺腺癌和潜在的高级别前列腺上皮内瘤变的区域。对于主PCa样本的子集，RNA原位杂交(ISH)用于鉴定确定的肿瘤区域中的靶mRNA表达。
■在原发性PCa样品中观察到最高的中值[177Lu]Lu-NeoB结合，而[177Lu]Lu-PSMA-617的中位数和总体结合在CRPC样品中最高。在3/17个CRPC样品中观察到最高的[177Lu]Lu-NeoB结合,其中一个样品没有显示[177Lu]Lu-PSMA-617结合。RNAISH分析显示mRNA表达和放射性药物结合之间的趋势，并证实了在放射性药物结合下观察到的原发性PCa中不同的GRPR和PSMA表达模式。
■我们的研究强调，GRPR靶向方法可以有助于改善PCa管理，并补充目前在早期和晚期PCa中应用的PSMA靶向策略。
