PSMA-Targeted Radiolabeled Peptide for Imaging and Therapy in Prostate Cancer: Preclinical Evaluation of Biodistribution and Therapeutic Efficacy.

Albumin-binding agents enhance tumor uptake of radiopharmaceuticals targeting prostate-specific membrane antigens (PSMAs) in radiotherapy. We synthesized PSMA-NARI-56, a molecule with both PSMA targeting activity and albumin-binding moiety, labeled with Lu as the therapeutic agent. The aim of this study was to determine the specific binding of Lu-PSMA-NARI-56 towards PSMA, assess its biodistribution, and evaluate therapeutic effectiveness by tumor-bearing mice. The effect of Lu-PSMA-NARI-56 viability of PSMA-positive cell (LNCaP) was evaluated. Biodistribution and endoradiotherapy studies were utilized to determine the distribution, targeting, and anti-tumor efficacy by tumor-bearing mice identified by In-PSMA-NARI-56. Lu-PSMA-NARI-56 exhibited a significant impact on the viability of the LNCaP cell. Biodistribution results revealed the maximum tumor uptake of Lu-PSMA-NARI-56 occurring within 24 h, reaching 40.56 ± 10.01%ID/g. In radionuclide therapy, at 58 days post-injection (p.i.), Lu-PSMA-NARI-56 demonstrated superior tumor inhibition (98%) compared to Lu-PSMA-617 (58%), and the mouse survival rate after 90 days of radiotherapy (90%) was also higher than that of Lu-PSMA-617 (30%) in LNCaP tumor-bearing mice. In the PSMA-positive animal model, Lu-PSMA-NARI-56 shows higher potential radiotheranostic and prolonged accumulation (identify by In-PSMA-NARI-56/nanoSPECT/CT image), offering the potential for improved treatment effectiveness and increased survival rates when compared to Lu-PSMA-617.