Xi Chen, Yue Sun, Fei Li, Ling Xi, Jun Dai, Can Zhao, Qingjian Dong
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The octanol-water partition coefficient for <sup>68</sup>Ga-DOTA-TMTP1 was -2.76 ± 0.08 and <sup>68</sup>Ga-DOTA-TMTP1 has showed excellent stability in in vitro studies. The cellular uptake and efflux of <sup>68</sup>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. <sup>68</sup>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 <sup>68</sup>Ga-DOTA-TMTP1 was thus validated. Overall, we have successfully synthesized <sup>68</sup>Ga-DOTA-TMTP1 with high yield and high specific activity and have demonstrated its potential role for highly metastatic tumor-targeted diagnosis.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087289/pdf/","citationCount":"0","resultStr":"{\"title\":\"<sup>68</sup>Ga-labeled TMTP1 radiotracer for PET imaging of cervical cancer.\",\"authors\":\"Xi Chen, Yue Sun, Fei Li, Ling Xi, Jun Dai, Can Zhao, Qingjian Dong\",\"doi\":\"10.62347/NFDH6303\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Molecular imaging enables visualization and characterization of biological processes that influence tumor behavior and response to therapy. 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引用次数: 0
摘要
分子成像技术可对影响肿瘤行为和治疗反应的生物过程进行可视化和特征描述。TMTP1(NVVRQ)肽对高度转移性肿瘤具有显著的亲和力,其潜在受体是氨肽酶 P2。在这项研究中,我们设计并合成了一种 68Ga 标记的环状 TMTP1 放射性示踪剂(68Ga-DOTA-TMTP1),用于宫颈癌的 PET 成像。这项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。68Ga-DOTA-TMTP1 的放射化学收率很高,放射化学纯度大于 95%。68Ga-DOTA-TMTP1的辛醇-水分配系数为-2.76 ± 0.08,68Ga-DOTA-TMTP1在体外研究中表现出优异的稳定性。68Ga-DOTA-TMTP1 在成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 中的细胞摄取和外流情况在 γ 计数器中进行了测量。68Ga-DOTA-TMTP1 在 HeLa 细胞中的吸收率高于 C-33A 细胞。过量的 TMTP1 可以阻断与 HeLa 和 C-33A 细胞的结合。在 microPET 图像上,HeLa 肿瘤在 60 分钟内清晰可见,而且 HeLa 肿瘤对放射性示踪剂的摄取量高于 C-33A 肿瘤。用 TMTP1 阻断后,HeLa 肿瘤的摄取明显减少,68Ga-DOTA-TMTP1 的特异性由此得到验证。总之,我们成功合成了 68Ga-DOTA-TMTP1,其产量高、特异性强,证明了它在高转移性肿瘤靶向诊断中的潜在作用。
68Ga-labeled TMTP1 radiotracer for PET imaging of cervical cancer.
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 68Ga-labeled cyclic TMTP1 radiotracer (68Ga-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 68Ga-DOTA-TMTP1 was high and the radiochemical purity was greater than 95%. The octanol-water partition coefficient for 68Ga-DOTA-TMTP1 was -2.76 ± 0.08 and 68Ga-DOTA-TMTP1 has showed excellent stability in in vitro studies. The cellular uptake and efflux of 68Ga-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. 68Ga-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 68Ga-DOTA-TMTP1 was thus validated. Overall, we have successfully synthesized 68Ga-DOTA-TMTP1 with high yield and high specific activity and have demonstrated its potential role for highly metastatic tumor-targeted diagnosis.
期刊介绍:
The scope of AJNMMI encompasses all areas of molecular imaging, including but not limited to: positron emission tomography (PET), single-photon emission computed tomography (SPECT), molecular magnetic resonance imaging, magnetic resonance spectroscopy, optical bioluminescence, optical fluorescence, targeted ultrasound, photoacoustic imaging, etc. AJNMMI welcomes original and review articles on both clinical investigation and preclinical research. Occasionally, special topic issues, short communications, editorials, and invited perspectives will also be published. Manuscripts, including figures and tables, must be original and not under consideration by another journal.