Molecular imaging and treatment of PSMA-positive prostate cancer with 99mTc radiolabeled aptamer-siRNA chimeras

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer (PCa). The aptamer (Apt) A10-3.2 can be used as a specific ligand for the early diagnosis and targeted treatment of PCa. siRNA-Apt has been used to therapeutically target PSMA-positive PCa. We aimed to synthesize a new type of molecular probe to facilitate the integration of diagnosis and treatment for PSMA-positive PCa.Chimeras were obtained by covalent linking PSMA Apt-A10-3.2 and the MDM2 siRNA. SHNH, a bifunctional chelating agent, was used to couple 99mTc with chimeras to synthesize a new molecular probe. Labeling efficiency, radiochemical purity, and stability were confirmed using a γ-well counter and Whatman paper No.1. SPECT imaging and biodistribution studies were performed on BALB/c mice bearing 22Rv1 or PC-3 xenografts. Tumor inhibition and cytotoxicity of Chimeras were evaluated. LNCaP, 22RV1, and PC-3 PCa cell lines were used for in vitro and in vivo experiments.[99mTc]Tc-chimeras showed high labeling efficiency (61.47% ± 2.85%, n = 3), radiochemical purity (>95%), and stability. Biodistribution studies and SPECT imaging with 99mTc-chimeras in mice bearing 22Rv1 xenografts demonstrated a high T/M ratio (4.63 ± 0.68, n = 3) and a high T/B ratio (3.61 ± 0.7, n = 3) at 2 h post-injection. 99mTc-chimeras showed rapid renal clearance. Compared with the PBS group, tumor growth in the chimera group was significantly inhibited (P < 0.01, n = 4), but there was no significant difference in body weight (p > 0.05, n = 4). H&E staining showed no obvious liver or kidney damage.Our study proved that [99mTc]Tc-Aptamer-siRNA chimeras could be used to diagnose and treat PSMA-positive PCa in vivo.