Cui Can, Hanyu Masayuki, Hatori Akiko, Zhang Yiding, Xie Lin, Ohya Tomoya, Fukada Masami, Suzuki Hisashi, Nagatsu Kotaro, Jiang Cuiping, Luo Rui, Shao Guoqiang, Zhang Mingrong, Wang Feng
Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical UniversityNanjing, China.
Department of Radiopharmaceutics Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and TechnologyChiba, Japan.
Am J Nucl Med Mol Imaging. 2017 Apr 15;7(2):40-52. eCollection 2017.
We radiolabeled a ligand, PSMA-617, of prostate-specific membrane antigen (PSMA) with copper-64 (Cu), to evaluate the metabolism, biodistribution, and potential of [Cu]PSMA-617 for PET imaging of prostate cancer. [Cu]PSMA-617 was synthesized by heating PSMA-617 with [Cu]CuCl in buffer solution at 90°C for 5 min. uptake was determined in two cell lines of prostate cancer. regional distributions were determined in normal and tumor-bearing mice. High radiolabeling efficiency of Cu for PSMA-617 yielded [Cu]PSMA-617 with >99% radiochemical purity. cellular uptake experiments demonstrated the specificity of [Cu]PSMA-617 for PSMA-positive LNCaP cells. Biodistribution observations of normal mice revealed high uptake of radioactivity in the kidney and liver. PET with [Cu]PSMA-617 visualized tumor areas implanted by PSMA-positive LNCaP cells in the mice. Two hours after the injection of [Cu]PSMA-617 into mice, a radiolabeled metabolite was observed in the blood, liver, urine, and LNCaP tumor tissues. [Cu]PSMA-617 was easily synthesized, and exhibited a favorable biodistribution in PSMA-positive tumors. Although this radioligand shows slow clearance for kidney and high liver uptake, change of its chelator moiety and easy radiolabeling may enable development of new Cu or Cu-labeled PSMA ligands for imaging and radiotherapy.
我们用铜 - 64（Cu）对前列腺特异性膜抗原（PSMA）的配体PSMA - 617进行放射性标记，以评估[Cu]PSMA - 617在前列腺癌PET成像中的代谢、生物分布及潜力。[Cu]PSMA - 617是通过将PSMA - 617与[Cu]CuCl在缓冲溶液中于90°C加热5分钟合成的。在两种前列腺癌细胞系中测定了摄取情况。在正常小鼠和荷瘤小鼠中测定了区域分布。Cu对PSMA - 617的高放射性标记效率产生了放射化学纯度>99%的[Cu]PSMA - 617。细胞摄取实验证明了[Cu]PSMA - 617对PSMA阳性LNCaP细胞的特异性。正常小鼠的生物分布观察显示肾脏和肝脏对放射性的摄取较高。用[Cu]PSMA - 617进行的PET成像显示了小鼠体内由PSMA阳性LNCaP细胞植入的肿瘤区域。向小鼠注射[Cu]PSMA - 617两小时后，在血液、肝脏、尿液和LNCaP肿瘤组织中观察到一种放射性标记的代谢物。[Cu]PSMA - 617易于合成，并且在PSMA阳性肿瘤中表现出良好的生物分布。尽管这种放射性配体在肾脏中的清除较慢且肝脏摄取较高，但其螯合剂部分的改变和易于放射性标记可能有助于开发用于成像和放射治疗的新型Cu或Cu标记的PSMA配体。
