Preparation, preclinical evaluation and preliminary clinical application of 64Cu-DOTATATE
10.3760/cma.j.cn321828-20240712-00255
- VernacularTitle:64Cu－DOTATATE的制备、临床前评价及初步临床应用
- Author:
Huanhuan LIU
1
;
Xiaojun ZHANG
1
;
Guangyu MA
1
;
Yue PAN
1
;
Jingfeng ZHANG
1
;
Hui WEN
1
;
Xiaodan XU
1
;
Ruimin WANG
1
;
Jinming ZHANG
1
Author Information
1. 解放军总医院第一医学中心核医学科，北京 100853
- Publication Type:Journal Article
- Keywords:
Neuroendocrine tumors;
Peptides;
Isotope labeling;
Copper;
Mice, nude
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2025;45(6):358-363
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To prepare domestic 64Cu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE), and to verify its distribution and preliminary diagnostic value in neuroendocrine tumors (NETs). Methods:DOTATATE was labeled with the domestic 64Cu to obtain 64Cu-DOTATATE. The lipophilicity, in vitro stability, and pharmacokinetics were studied. Biodistribution experiments and microPET imaging were performed on NCI-H727 (somatostatin receptor (SSTR)2 positive expression) tumor-bearing nude mice. The preliminary clinical applications were conducted on 10 NETs patients (5 males, 5 females; age (58.5±13.0) years) from Chinese PLA General Hospital between May 2023 and April 2024. Data were analyzed by using independent-sample t test. Results:64Cu-DOTATATE was successfully prepared with the radiochemical purity greater than 98%, log P of -2.609±0.051 and good stability. Pharmacokinetic experiments in BALB/c mice suggested rapid blood clearance of the drug (elimination half-time of 22.78min). Biodistribution results in tumor-bearing mice showed that 64Cu-DOTATATE was mainly metabolized through the liver and kidneys, with significant tumor uptake at 1h ((2.519±0.273) percentage activity of injection dose per gram of tissue (%ID/g)) and sustained high uptake at 24h ((4.331±0.549)%ID/g). MicroPET imaging of tumor-bearing mice showed a slight increase in uptake and good retention at 24h, with a significant statistical difference compared to the blocked group ((2.197±0.250) vs (0.985±0.064) % ID/g; t=6.40, P=0.008). The tumor/liver ratios were 0.075±0.007, 0.083±0.011, 0.118±0.005, 0.263±0.031 at 1, 2, 6 and 24h, respectively. Preliminary clinical application indicated that 64Cu-DOTATATE exhibited good targeting in patients, and the liver radioactivity distribution was moderate (SUV max=10.62±3.46), providing good image quality. Conclusion:Domestic 64Cu-DOTATATE PET/CT imaging is a promising imaging evaluation method in NETs with the value for further clinical research.
