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.

Objective:To explore the optimal labeling conditions of 177Lu-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)- D-Phe1-Tyr3-Thr8-octreotide (TATE), and evaluate its biodistribution and imaging characteristics in mice. Methods:The reaction temperature, pH, reaction time and other labeling conditions were changed to realize the rapid labeling of NOTATATE by 177Lu. The optimal labeling conditions, radiochemical purity, in vitro stability, plasma protein binding rate, and lipid-water partition coefficient were determined. Twenty-four normal KM mice were divided into 6 groups by random number table method. After injected with 3.7 MBq 177Lu-NOTATATE through tail vein, they were sacrificed at 0.5, 1, 4, 24 h and 4, 6 d respectively to research the biological distribution (injection dose rate per gram of tissue percentage, %ID/g). Six normal mice were randomly divided into 2 groups and injected with 11.1 MBq 177Lu-NOTATATE and 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)TATE, respectively. SPECT planar imaging was performed at 1, 2, 3 h after injection. Another 8 mice were divided into 4 groups, injected with 3.7, 7.4, 18.5 MBq 177Lu-NOTATATE and saline respectively for an acute toxicity test. Results:At pH 5 and reaction temperature between 95 ℃ and 100 ℃ for 15 min, the labeling rate could reach more than 98%. After being placed in human serum for 24 h, the radiochemical purity was still higher than 95%. The plasma protein binding rate of 177Lu-NOTATATE was (58.6±1.9)% and the lipid-water partition coefficient was 0.048±0.014. In normal mice, the concentration of radioactivity is mainly in the liver, kidney and spleen, especially in the kidney (up to (29.120±1.204) %ID/g after 0.5 h of injection), which is less distributed in the blood and excreted rapidly. Compared with 177Lu-DOTATATE, 177Lu-NOTATATE was excreted faster by the kidney. The toxicity study results revealed that no damage was observed in mice of each group, and no obvious damage or inflammatory changes were observed in organ tissue sections. Conclusions:The optimal labeling condition of 177Lu-NOTATATE were determined in this study. The physical, chemical, and biological properties of 177Lu-NOTATATE were proved to be good and safe, and it was excreted faster by the kidney than 177Lu-DOTATATE. The results of this study lay a foundation for further clinical transformation research.

Prostate specific membrane antigen (PSMA) radioligand therapy (RLT) is effective in metastatic castration-resistant prostate cancer (mCRPC). However, PSMA RLT can cause radiation damage to salivary glands, especially 225Ac/ 177Lu-PSMA-617. Radiation-related salivary glands damage can cause xerostomia, reduce the quality of life, and even limit the dose of radiopharmaceuticals and reduce the efficacy of tumor treatment. At present, there are few literatures on PSMA RLT related salivary glands damage in China. In this article, radiation-related salivary glands damage and the related protective measures during 225Ac/ 177Lu-PSMA-617 RLT are reviewed based on domestic and foreign studies.