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

Area of Science:

• Radiochemistry and Nuclear Medicine
• Oncology
• Molecular Imaging

Background:

• Prostate-specific membrane antigen (PSMA) is a key target for prostate cancer (PCa) diagnosis and therapy.
• Development of effective PSMA-targeting tracers is crucial for improving PCa management.
• Existing tracers may have limitations in specificity or in vivo retention.

Purpose of the Study:

• To design and synthesize a novel dimeric PSMA-targeting ligand, PSMA-DIM.
• To evaluate the in vitro and in vivo performance of the radiolabeled tracer [⁶⁸Ga]-Ga-PSMA-DIM for PSMA-positive prostate cancer models.

Main Methods:

• Synthesis of the dimeric ligand PSMA-DIM based on the Glu-urea-Lys pharmacophore with specific motifs.
• Radiolabeling of PSMA-DIM with Gallium-68 ([⁶⁸Ga]).
• Assessment of radiochemical purity, stability, binding affinity (K_d), cell uptake, and internalization in PCa cell lines (LNCaP, 22Rv1, PC-3).
• Evaluation of in vivo tumor uptake, biodistribution, and retention in tumor-bearing mouse models.

Main Results:

• [⁶⁸Ga]-Ga-PSMA-DIM demonstrated high radiochemical purity (>98%) and stability.
• The tracer exhibited high binding affinity (K_d = 37.09 ± 13.53 nM) and significantly higher uptake/internalization in LNCaP cells compared to 22Rv1 or PC-3 cells.
• The tracer showed a favorable elimination half-life (99.55 min) and notable in vivo retention.
• High tumor uptake was observed in LNCaP and 22Rv1 xenografts, with sustained retention over 3 hours, differentiating from PC-3 xenografts.

Conclusions:

• [⁶⁸Ga]-Ga-PSMA-DIM is a highly specific and effective PSMA-targeting tracer.
• The tracer demonstrates sensitive differentiation of PSMA expression levels in preclinical models.
• Its notable in vivo retention suggests potential for improved diagnostic imaging in prostate cancer.