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68Ga-labeled TMTP1 radiotracer for PET imaging of cervical cancer

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单位: [1]Department of Obstetrics and Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China [2]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 [3]Department of Nuclear Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China [4]Department of Pathology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China [5]Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
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关键词: Cervical cancer Ga-68-DOTA-TMTP1 positron emission tomography molecular imaging metastasis

摘要:
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-68-labeled cyclic TMTP1 radiotracer (Ga-68-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-68-DOTA-TMTP1 was high and the radiochemical purity was greater than 95%. The octanol-water partition coefficient for Ga-68-DOTA-TMTP1 was -2.76 +/- 0.08 and Ga-68-DOTA-TMTP1 has showed excellent stability in in vitro studies. The cellular uptake and efflux of Ga-68-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 gamma counter. Ga-68-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-68-DOTA-TMTP1 was thus validated. Overall, we have successfully synthesized Ga-68-DOTA-TMTP1 with high yield and high specific activity and have demonstrated its potential role for highly metastatic tumor-targeted diagnosis.

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大类 | 4 区 医学
小类 | 4 区 核医学
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Q3 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

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第一作者单位: [1]Department of Obstetrics and Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China [2]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 [5]Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
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通讯机构: [3]Department of Nuclear Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China [4]Department of Pathology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China [*1]Department of Nuclear Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China [*2]Department of Pathology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China
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