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

## TL;DR

This study evaluates a new radiolabeled peptide for prostate cancer imaging and therapy, showing improved tumor targeting and survival rates in mice.

## Contribution

A novel PSMA-targeted radiolabeled peptide with an albumin-binding moiety is developed and tested for enhanced radiotheranostic performance.

## Key findings

- 177Lu-PSMA-NARI-56 showed significant tumor uptake of 40.56 ± 10.01%ID/g at 24 hours.
- The compound demonstrated 98% tumor inhibition and 90% survival rate in mice compared to 58% and 30% for 177Lu-PSMA-617.
- 177Lu-PSMA-NARI-56 exhibited prolonged tumor accumulation and superior therapeutic efficacy in PSMA-positive models.

## Abstract

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 177Lu as the therapeutic agent. The aim of this study was to determine the specific binding of 177Lu-PSMA-NARI-56 towards PSMA, assess its biodistribution, and evaluate therapeutic effectiveness by tumor-bearing mice. The effect of 177Lu-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 111In-PSMA-NARI-56. 177Lu-PSMA-NARI-56 exhibited a significant impact on the viability of the LNCaP cell. Biodistribution results revealed the maximum tumor uptake of 177Lu-PSMA-NARI-56 occurring within 24 h, reaching 40.56 ± 10.01%ID/g. In radionuclide therapy, at 58 days post-injection (p.i.), 177Lu-PSMA-NARI-56 demonstrated superior tumor inhibition (98%) compared to 177Lu-PSMA-617 (58%), and the mouse survival rate after 90 days of radiotherapy (90%) was also higher than that of 177Lu-PSMA-617 (30%) in LNCaP tumor-bearing mice. In the PSMA-positive animal model, 177Lu-PSMA-NARI-56 shows higher potential radiotheranostic and prolonged accumulation (identify by 111In-PSMA-NARI-56/nanoSPECT/CT image), offering the potential for improved treatment effectiveness and increased survival rates when compared to 177Lu-PSMA-617.