Low-Level Endogenous PSMA Expression in Nonprostatic Tumor Xenografts Is Sufficient for In Vivo Tumor Targeting and Imaging
Low-Level Endogenous PSMA Expression in Nonprostatic Tumor Xenografts Is Sufficient for In Vivo Tumor Targeting and Imaging
复制标题
DOI：
10.2967/jnumed.117.191221
复制
发表时间：
2018-03-01
影响因子：
9.3
通讯作者：
Pomper, Martin G.
中科院分区：
文献类型：
--
作者：
Nimmagadda, Sridhar;Pullambhatla, Mrudula;Pomper, Martin G.
前列腺特异性膜抗原（PSMA）在前列腺癌和其他实体瘤的新生血管中高度表达。PSMA的非前列腺表达仅在非前列腺癌的新生血管内皮细胞中有报道;然而，关于PSMA在上皮细胞中表达的报道很少。在此，我们描述了PSMA在非前列腺上皮细胞中的表达，并描述了PSMA结合剂非侵入性检测该表达的潜力。方法：从公开可用的基因组数据库中提取PSMA表达数据。通过定量逆转录聚合酶链反应、流式细胞术和蛋白质印迹法，在几种非前列腺细胞系和黑色素瘤和小细胞肺癌（SCLC）来源的异种移植物中，对PSMA表达的基因组数据进行了实验验证。使用基于PSMA的核和光学成像剂并通过生物分布、阻断和离体分子表征研究，进一步确立了PSMA检测在这些肿瘤模型中的可行性。结果：我们发现一小部分非前列腺癌细胞系和肿瘤表达PSMA。重要的是，PSMA表达足够高以使用基于PSMA的核和光学成像剂对建立的黑素瘤和SCLC异种移植物成像。结论：这些结果表明，PSMA在非前列腺肿瘤中的表达可能不仅限于内皮细胞，还可能包括非前列腺癌的实体瘤组织，包括黑色素瘤和SCLC。我们的观察结果表明，更广泛的适用性PSMA靶向成像和治疗。
Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and within the neovasculature of other solid tumors. The nonprostatic expression of PSMA has been reported exclusively within the neovasculature endothelial cells of nonprostatic cancers; however, there are few reports on PSMA expression in epithelial cells. Herein, we describe PSMA expression in nonprostatic epithelial cells and characterize the potential of PSMA-binding agents to noninvasively detect that expression. Methods: PSMA expression data were extracted from publicly available genomic databases. Genomic data were experimentally validated for PSMA expression-by quantitative reverse transcription polymerase chain reaction, flow cytometry, and Western blotting-in several nonprostatic cell lines and xenografts of melanoma and small cell lung cancer (SCLC) origin. The feasibility of PSMA detection in those tumor models was further established using PSMA-based nuclear and optical imaging agents and by biodistribution, blocking, and ex vivo molecular characterization studies. Results: We discovered that a small percentage of nonprostatic cancer cell lines and tumors express PSMA. Importantly, PSMA expression was sufficiently high to image established melanoma and SCLC xenografts using PSMA-based nuclear and optical imaging agents. Conclusion: These results indicate that PSMA expression in nonprostatic tumors may not be limited to the endothelium but may also include solid tumor tissue of nonprostatic cancers including melanoma and SCLC. Our observations indicate broader applicability of PSMA-targeted imaging and therapeutics.