68Ga-DOTA-TFpep Targeting the Thomsen-Friedenreich Antigen for PET Imaging
文献类型：期刊论文
| 作者 | Ju, Nianting5,6; Tan, Boyu1,2,6; Lou, Hongyue6; Zhang, Ying6; Qian, Kun6; Qu, Chunrong6; Luo, Quanyong5; Cheng, Zhen3,4,6 |
| 刊名 | MOLECULAR PHARMACEUTICS
 |
| 出版日期 | 2025-12-15 |
| 页码 | 8 |
| 关键词 | Ga-68 peptide PET imaging radiolabeling Thomsen-Friedenreich antigen |
| ISSN号 | 1543-8384 |
| DOI | 10.1021/acs.molpharmaceut.5c01313 |
| 英文摘要 | As an important tumor-associated carbohydrate antigen, the Thomsen-Friedenreich (T or TF) antigen has become an attractive target for tumor diagnosis and treatment. However, there has been very limited success in developing peptide- and small-molecule-based radiopharmaceuticals for this important target. Currently, only Cu-64-NO2A-TFpep has been reported as a radiolabeled peptide targeting the TF antigen, and it shows a low tumor-to-liver ratio due to Cu-64 retention in the liver. In this study, a novel PET probe targeting the TF antigen (DOTA-TFpep) was synthesized using 2,2 ',2 '',2 & tprime;-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) chelator for increasing the hydrophilic property and for radiolabeling with different radionuclides. DOTA-TFpep was then radiolabeled with Ga-68 for positron emission tomography (PET) imaging of breast tumors expressing the TF antigen. Ga-68-DOTA-TFpep was confirmed by radio-HPLC with a purity greater than 98% and high stability in PBS. Immunofluorescence analysis confirmed the TF antigen expression of 4T1 and K1 cell lines. Cell uptake studies confirmed its targeting specificity. Further in vivo biodistribution studies in high (4T1) and low (K1) TF antigen-expression xenograft models demonstrated the favorable pharmacokinetics property of the probe. PET imaging and biodistribution showed that Ga-68-DOTA-TFpep exhibited specific tumor uptake. Moreover, compared with the widely studied Cu-64-NO2A-TFpep, Ga-68-DOTA-TFpep showed lower liver uptake and a higher tumor-to-liver ratio (1.31 +/- 0.20 for Cu-64-NO2A-TFpep and 0.48 +/- 0.15 for Ga-68-DOTA-TFpep at 120 min after injection). In summary, this study demonstrates the synthesis and evaluation of the TF antigen-targeting probe Ga-68-DOTA-TFpep. It shows favorable in vivo tumor imaging properties, highlighting it as a promising molecular probe targeting the TF antigen. |
| WOS关键词 | MONOCLONAL-ANTIBODY ; HUMAN BREAST ; RENAL UPTAKE ; PEPTIDES ; CARCINOMA ; CHELATORS ; AFFINITY ; JAA-F11 ; BIND ; DOTA |
| 资助项目 | Science and Technology Commission of Shanghai Municipality[24YF2756100] ; Ningbo Major Research and Development Plan Project[2024Z214] ; Natural Science Foundation of Shanghai Municipality[82472091] ; China Postdoctoral Science Foundation[GZC20232842] ; Shandong Laboratory Program[SYS202205] ; Shanghai Post-doctoral Excellence Program[2024709] ; National Health and Medical Research Council (NHMRC)[2024709] |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001640157500001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322372]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Qu, Chunrong; Luo, Quanyong; Cheng, Zhen |
| 作者单位 | 1.ShanghaiTech Univ, Sch Biomed Engn, Shanghai 201210, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China 4.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China 5.Shanghai Jiao Tong Univ Sch Med, Dept Nucl Med, Shanghai Peoples Hosp Affiliated 6, Shanghai 200233, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Mol Imaging Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ju, Nianting,Tan, Boyu,Lou, Hongyue,et al. 68Ga-DOTA-TFpep Targeting the Thomsen-Friedenreich Antigen for PET Imaging[J]. MOLECULAR PHARMACEUTICS,2025:8. |
| APA | Ju, Nianting.,Tan, Boyu.,Lou, Hongyue.,Zhang, Ying.,Qian, Kun.,...&Cheng, Zhen.(2025).68Ga-DOTA-TFpep Targeting the Thomsen-Friedenreich Antigen for PET Imaging.MOLECULAR PHARMACEUTICS,8. |
| MLA | Ju, Nianting,et al."68Ga-DOTA-TFpep Targeting the Thomsen-Friedenreich Antigen for PET Imaging".MOLECULAR PHARMACEUTICS (2025):8. |
入库方式： OAI收割
来源：上海药物研究所
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