Xi Chen, Yue Sun, Fei Li, Ling Xi, Jun Dai, Can Zhao, Qingjian Dong
{"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. 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 <sup>68</sup>Ga-labeled cyclic TMTP1 radiotracer (<sup>68</sup>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 <sup>68</sup>Ga-DOTA-TMTP1 was high and the radiochemical purity was greater than 95%. 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":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of nuclear medicine and molecular imaging","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.62347/NFDH6303","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
引用次数: 0
Abstract
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.