Preparation and preliminary biological evaluation of domestic 177Lu-PSMA-617 / 中华核医学与分子影像杂志

ABSTRACT

Objective:To synthesize 177Lu-prostate-specific membrane antigen (PSMA)-617 with domestic 177Lu (made in China), and explore its optimal labeling condition, biodistribution, stability, and safety. Methods:177Lu-PSMA-617 was prepared with domestic 177Lu by a manual method. The optimal labeling condition, radiochemical purity, stability ( in vivo and in vitro), lipid-water partition coefficient, and plasma protein binding rate were determined. The uptake rate of 177Lu-PSMA-617 was evaluated by using 22RV1 cells. Biodistribution and SPECT/CT imaging were performed on normal mice with imported 177Lu-PSMA-617 as control group. The blood routine test was performed to evaluate the safety. Results:The best labeling result of domestic 177Lu-PSMA-617 can be obtained under the following conditions pH=4.5, 100 ℃ for 30 min. And the radiochemical purity was ≥99%. The product was stable in vivo and in vitro, with the radiochemical purity >95% in 72 h. The plasma protein binding rate was (35.3±5.3)%, the lipid-water partition coefficient was -2.27±0.06, and the specific uptake rate of domestic 177Lu-PSMA-617 by 22RV1 cells reached the highest in 1 h ((7.58±0.84)%), which was slightly lower than the imported 177Lu-PSMA-617 ((7.86±0.96)%), but there was no significant difference between them ( t=-0.439, P>0.05). The distribution and SPECT/CT imaging of normal mice showed that domestic and imported 177Lu-PSMA-617 in blood were cleared quite fast, and both of them were excreted mainly through the kidneys. No obvious adverse reactions were found in the toxicity test of domestic and imported 177Lu-PSMA-617. There was no obvious abnormality in blood routine and liver and kidney metabolism. Conclusion:The domestic 177Lu-PSMA-617 has many advantages, such as qualified quality control, good biological properties and safety, which support its potential application value in diagnosis of prostatic neoplasms.