A Preclinical Study of an ¹²⁵I-Labeled PSMA Ligand for Prostate-Cancer Puncture

Prostate cancer (PCa) is characterized by high expression of prostate-specific 1membrane antigen (PSMA), a type II transmembrane protein. Prostate-specific membrane antigen positron emission tomography (PSMA PET) has high sensitivity and specificity and can therefore be potentially used to detect PCa. Exploiting the advantages of PSMA PET imaging, in this study, we aim to develop a novel radiopharmaceutical to facilitate biopsy punching of PCa.

We synthesized a high-affinity radiopharmaceutical of PSMA (¹²⁵I-PSMA-7). We evaluated the properties of ¹²⁵I-PSMA-7, including the purity, stability, affinity, partition coefficient, and toxicity. (PSMA+) 22Rv1 and (PSMA-) PC3 cell lines were used to evaluate ¹²⁵I-PSMA-7 in vitro. BALB/c nude mice bearing 22Rv1 and PC3 xenografts were used for biodistribution and imaging. The uptake of the main organs was evaluated in vivo using single photon emission computed tomography (SPECT).

¹²⁵I-PSMA-7 had a purity of 99.6% and remained stable for seven days and was therefore always safe to use. ¹²⁵I-PSMA-7 had a Ki of 4.037 × 10^-11 and a partition coefficient of -1.80. The results of in vitro cellular experiments showed a high uptake by 22Rv1 cells (ranging from 2.88 ± 0.14 IA%/10⁶ at 5 min to 61.98 ± 3.43 IA%/10⁶ at 24 h, where the internalization was 46.1% at 1 h and 88.06% at 24 h). However, the uptake of PC3 cells was very low (ranging from 0.34 ± 0.08 IA%/10⁶ at 5 min to 1.60 ± 0.15 IA%/10⁶ at 24 h). The tumors' uptake of ¹²⁵I-PSMA-7 ranged from 9.02 ± 0.30 ID%/g at 1 h to 4.11 ± 1.04 ID%/g at 7 d and the tumor/muscle ratios and tumor/blood ratios increased over time. In addition, we used γ-counter to measure cpm per milligram of tumor and muscle on days 4 and 7. The background on day 4 is 42 cpm and the tumor is 1739 cpm/mg and the muscle is 45 cpm/mg, and the background on day 7 is 74 cpm and the tumor is 1404cpm/mg and the muscle is 32 cpm/mg. At 1 h post-injection, the high uptake of ¹²⁵I-PSMA-7 resulted in clear delineation of 22Rv1-derived tumors upon imaging. By comparison, 22Rv1-blocking mice took up less ¹²⁵I-PSMA-7.

These results show that ¹²⁵I-PSMA-7 is a promising radiotracer that could be used to puncture the prostate. ¹²⁵I-PSMA-7 could be applied to targeted biopsy, reducing the need for saturated biopsy.