Preclinical Evaluation Study of 68Ga-Labeled PSMA-Targeted Dimer Probe.

The development of tracers targeting prostate-specific membrane antigen (PSMA) has great significance for improving the diagnosis and treatment of prostate cancer (PCa). In this study, a dimeric PSMA-targeting ligand, PSMA-DIM, has been designed and synthesized based on the structure of the Glu-urea-Lys pharmacophore by introducing 4-(p-iodophenyl) butyric acid and PEG4 motifs. [ 68 Ga]-Ga-PSMA-DIM exhibited high radiochemical purity (>98%) and stability, with a K d value for LNCaP cells of 37.09 ± 13.53 nM. The uptake and internalization of [ 68 Ga]-Ga-PSMA-DIM by LNCaP cells were significantly higher compared to 22Rv1 or PC-3 cells. The elimination half-life of [ 68 Ga]-Ga-PSMA-DIM from the plasma was calculated to be 99.55 min, indicating a significant extension of retention time in vivo. The peak tumor uptake of [ 68 Ga]-Ga-PSMA-DIM in LNCaP and 22Rv1 tumor-bearing mice was 4.19 ± 0.65 %ID/mL and 4.08 ± 0.47 %ID/mL, respectively, which was significantly higher than that observed in the PC-3 tumor-bearing mice (2.71 ± 0.70 %ID/mL). Moreover, [ 68 Ga]-Ga-PSMA-DIM maintained relatively high uptake in LNCaP and 22Rv1 tumors even after 3 h (3.84 ± 0.50 %ID/mL and 3.59 ± 0.57 %ID/mL, respectively). In conclusion, [ 68 Ga]-Ga-PSMA-DIM could sensitively and specifically differentiate models with varying PSMA expression levels and show notable retention in vivo.