Chen Xi, Sun Yue, Li Fei, Xi Ling, Dai Jun, Zhao Can, Dong Qingjian
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, Hubei, China.
National Clinical Research Centre for Obstetrics and Gynaecology, Cancer Biology Research Centre (Key Laboratory of The Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, Hubei, China.
Am J Nucl Med Mol Imaging. 2024 Apr 25;14(2):110-121. doi: 10.62347/NFDH6303. eCollection 2024.
Molecular imaging enables visualization and characterization of biological processes that influence tumor behavior and response to therapy. The TMTP1 (NVVRQ) peptide has shown remarkable affinity to highly metastatic tumors and and its potential receptor is aminopeptidase P2. In this study, we have designed and synthesized a Ga-labeled cyclic TMTP1 radiotracer (Ga-DOTA-TMTP1), for PET imaging of cervical cancer. The goal of this study was to investigate the properties of this radiotracer and its tumor diagnostic potential. The radiochemical yield of Ga-DOTA-TMTP1 was high and the radiochemical purity was greater than 95%. The octanol-water partition coefficient for Ga-DOTA-TMTP1 was -2.76 ± 0.08 and Ga-DOTA-TMTP1 has showed excellent stability in in vitro studies. The cellular uptake and efflux of Ga-DOTA-TMTP1 in paired highly metastatic and lowly metastatic cervical cancer cell line HeLa and C-33A as well as normal cervical epithelial cell line End1 were measured in a γ counter. Ga-DOTA-TMTP1 exhibited higher uptake in HeLa cells than in C-33A cells. The binding to HeLa and C-33A cells could be blocked by excess TMTP1. On microPET images, HeLa tumors were clearly visualized within 60 min and the uptake of the radiotracer in HeLa tumors was higher than that of C-33A tumors. After blocking with TMTP1, HeLa tumors uptake was significantly reduced and the specificity Ga-DOTA-TMTP1 was thus validated. Overall, we have successfully synthesized Ga-DOTA-TMTP1 with high yield and high specific activity and have demonstrated its potential role for highly metastatic tumor-targeted diagnosis.
分子成像能够可视化并表征影响肿瘤行为和治疗反应的生物学过程。TMTP1（NVVRQ）肽已显示出对高转移性肿瘤具有显著亲和力，其潜在受体是氨肽酶P2。在本研究中，我们设计并合成了一种用于宫颈癌PET成像的镓标记环状TMTP1放射性示踪剂（Ga-DOTA-TMTP1）。本研究的目的是研究这种放射性示踪剂的特性及其肿瘤诊断潜力。Ga-DOTA-TMTP1的放射化学产率高，放射化学纯度大于95%。Ga-DOTA-TMTP1的正辛醇-水分配系数为-2.76±0.08，并且在体外研究中显示出优异的稳定性。在γ计数器中测量了Ga-DOTA-TMTP1在配对的高转移性和低转移性宫颈癌细胞系HeLa和C-33A以及正常宫颈上皮细胞系End1中的细胞摄取和流出。Ga-DOTA-TMTP1在HeLa细胞中的摄取高于C-33A细胞。与HeLa和C-33A细胞的结合可被过量的TMTP1阻断。在微型PET图像上，HeLa肿瘤在60分钟内清晰可见，并且放射性示踪剂在HeLa肿瘤中的摄取高于C-33A肿瘤。用TMTP1阻断后，HeLa肿瘤摄取显著降低，从而验证了Ga-DOTA-TMTP1的特异性。总体而言，我们成功地高产率、高比活度地合成了Ga-DOTA-TMTP1，并证明了其在高转移性肿瘤靶向诊断中的潜在作用。
