Foss Catherine A, Mease Ronnie C, Fan Hong, Wang Yuchuan, Ravert Hayden T, Dannals Robert F, Olszewski Rafal T, Heston Warren D, Kozikowski Alan P, Pomper Martin G
Johns Hopkins University, Baltimore, Maryland 21287-2182, USA.
Clin Cancer Res. 2005 Jun 1;11(11):4022-8. doi: 10.1158/1078-0432.CCR-04-2690.
Prostate-specific membrane antigen (PSMA) is a cell surface protein that is overexpressed in prostate cancer, including hormone-refractory and metastatic disease. Our goal in this study was to develop a series of PSMA-based imaging agents for clinical use.
We have synthesized and evaluated the in vivo biodistribution of two radiolabeled urea derivatives that have high affinity for PSMA in severe combined immunodeficient mice harboring MCF-7 (breast, PSMA-negative), PC-3 (prostate, PSMA-negative), and LNCaP (prostate, PSMA-positive) xenografts. Radiopharmaceutical binding selectivity and tumor uptake were also evaluated in vivo using dedicated small animal positron emission tomography, single photon emission computed tomography, and gamma scintigraphic imaging devices. N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-[(11)C]methyl-L-cysteine ([(11)C]DCMC K(i), 3.1 nmol/L) and N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-[(125)I]iodo-L-tyrosine ([(125)C]DCIT K(i), 1.5 nmol/L) were synthesized using [(11)C]CH(3)I and with [(125)I]NaI/Iodogen, respectively.
At 30 minutes postinjection, [(11)C]DCMC and [(125)I]DCIT showed tumor/muscle ratios of 10.8 and 4.7, respectively, with clear delineation of LNCaP-derived tumors on imaging. MCF-7- and PC-3-derived tumors showed significantly less uptake of [(11)C]DCMC or [(125)I]DCIT.
These results show the feasibility of imaging PSMA-positive prostate cancer using low molecular weight agents.
前列腺特异性膜抗原（PSMA）是一种细胞表面蛋白，在前列腺癌中过度表达，包括激素难治性和转移性疾病。本研究的目标是开发一系列基于PSMA的临床用成像剂。
我们合成并评估了两种放射性标记的尿素衍生物在携带MCF-7（乳腺癌，PSMA阴性）、PC-3（前列腺癌，PSMA阴性）和LNCaP（前列腺癌，PSMA阳性）异种移植瘤的严重联合免疫缺陷小鼠体内的生物分布，这两种衍生物对PSMA具有高亲和力。还使用专用的小动物正电子发射断层扫描、单光子发射计算机断层扫描和γ闪烁成像设备在体内评估放射性药物的结合选择性和肿瘤摄取。分别使用[¹¹C]CH₃I和[¹²⁵I]NaI/碘珠合成了N-[N-[(S)-1,3-二羧基丙基]氨基甲酰基]-S-[(¹¹C)]甲基-L-半胱氨酸（[¹¹C]DCMC，Kᵢ为3.1 nmol/L）和N-[N-[(S)-1,3-二羧基丙基]氨基甲酰基]-S-3-[(¹²⁵I)]碘代-L-酪氨酸（[¹²⁵I]DCIT，Kᵢ为1.5 nmol/L）。
注射后30分钟，[¹¹C]DCMC和[¹²⁵I]DCIT的肿瘤/肌肉比值分别为10.8和4.7，成像时LNCaP来源的肿瘤清晰可见。MCF-7和PC-3来源的肿瘤对[¹¹C]DCMC或[¹²⁵I]DCIT的摄取明显较少。
这些结果表明使用低分子量试剂对PSMA阳性前列腺癌进行成像的可行性。
