Objective To evaluate the potential of 77Lu-prostate specific membrane antigen(PSMA)-3Q in the treatment of metastatic castration-resistant prostate cancer(mCRPC)and compare it with 177 Lu-PSMA-I&T.Methods 177Lu-PSMA-3Q was prepared and the quality control and stability testing were per-formed.Pharmacokinetic evaluation and biodistribution of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T were con-ducted in normal BALB/c mice and 22Rv1 tumor-bearing mice.SPECT imaging was performed on 2 patients(60 and 76 years old)with mCRPC from Chinese PLA General Hospital at 24,72,and 120 h after injec-tion of 177Lu-PSMA-3Q or 177Lu-PSMA-I&T((7.40±0.74)GBq).Data were analyzed by using independent-sample t test.Results 177Lu-PSMA-3Q was prepared with the total activity of 74 GBq,the yield rate of 95％(uncorrected),and the radiochemical purity was still above 95％after 168 h at room temperature.The distribution half-lives of 177Lu-PSMA-3Q and 177 Lu-PSMA-I&T were(0.75±0.22)and(0.86±0.19)min,and the clearance half-lives were(24.74±3.77)and(29.53±3.42)min.Biodistribution of normal mice showed that the uptake values in the liver,lungs,and kidneys 5 d after injection of 177Lu-PSMA-3Q were lower than those of 177 Lu-PSMA-I&T(t values:4.24-8.36,all P＜0.05).The tumor uptake of 177 Lu-PSMA-3Q after 24 h injection was the highest and was higher than that of 177 Lu-PSMA-I&T((0.856±0.183)vs(0.579±0.126)percentage activity of injection dose per gram of tissue(％ID/g);t=2.78,P=0.024)in 22Rv1 tumor-bearing mice.The rapid clearance pattern resulted in a higher tumor/muscle(T/M)ratio for 177Lu-PSMA-3Q(99.604±11.106),which was significantly higher than that for 177Lu-PSMA-I&T(45.078±10.444;t=7.80,P＜0.001).According to SPECT imaging of patients with mCRPC,the residual lesion counts of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T at 120 h accounted for 0.32±0.05 and 0.58±0.04 of those at 24 h,with significant difference(t=7.62,P=0.002).Conclusion 177Lu-PSMA-3Q is easy to label,and has high yield and radiochemical purity,good stability,excellent biological performance,good targeting ability in patients,longer retention time,and fast background clearance rate,which is an ideal prostate cancer treat-ment drug targeting PSMA.
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