Preparation and tumor-specific molecular imaging of a novel PET probe targeting angiotensin converting enzyme 2 / 中华核医学与分子影像杂志

ABSTRACT

Objective:To prepare a novel molecular imaging probe targeting angiotensin converting enzyme (ACE) 2 by using 68Ga labeled with 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-DX600, then the probe was evaluated in cervical cancer model by microPET/CT imaging. Methods:68Ga labeled DOTA-DX600 at 95 ℃, and the quality control, stability in vitro and lipid-water partition coefficient (log P) were tested. Tumor-bearing mouse models were constructed using stably transfected ACE2 highly expressed cervical cancer cells (Hela). The distribution and uptake of 68Ga-DOTA-DX600 in normal KM mice and tumor-bearing mice were determined by microPET/CT imaging, and the maximum standardized uptake value (SUV max) of the main organs and tumors were obtained by semi-quantitative analysis of the region of interest (ROI). Results:The preparation time of 68Ga-DOTA-DX600 was about 20 min, the specific activity of the probe was (18.74±3.72)×10 6 GBq/mol, the labeling rate was 82.3%, and the radiochemical purity was about 99% after purification. After placement in saline or 5% human serum albumin (HSA) solution at room temperature for 2 h, the radiochemical purity of the probe was more than 96%. The lipid-water partition coefficient (log P) was -2.44 ±0.04 ( n=3), which indicated as a good hydrophilicity. In normal KM mice, 68Ga-DOTA-DX600 metabolized faster in the blood and mainly distributed in the kidneys. The probe showed good tumor targeting ability in the tumor-bearing mice and the SUV max of the tumor were 0.25±0.01 and 0.21±0.01 at 30 min and 60 min after injection, respectively, and the tumor uptake was inhibited by DX600. Conclusion:68Ga-DOTA-DX600 can be obtained conveniently and fast and shows a good targeting ability to tumors, which provide potential application value for researches on targeting ACE2.