Integrating PET and Fluorescence Imaging with a Novel PSMA-ICG Conjugate for Prostate Cancer Management

Area of Science:

• Nuclear medicine and molecular imaging
• Oncology and cancer diagnostics
• Radiopharmaceutical chemistry

Background:

• Prostate cancer (PCa) poses a significant global health challenge.
• Current preoperative imaging lacks the sensitivity for accurate PCa diagnosis.
• Novel imaging probes are crucial for improving PCa detection and treatment.

Purpose of the Study:

• To design, synthesize, and evaluate a novel PET/fluorescence dual-modality probe, [68Ga]Ga-XY-PSMA-ICG.
• To assess the probe's affinity, specificity, biodistribution, pharmacokinetics, and dosimetry.
• To validate its efficacy in preclinical models and initial human studies for prostate cancer imaging.

Main Methods:

• Synthesis and radiolabeling of [68Ga]Ga-XY-PSMA-ICG via a 14-step process.
• In vitro and in vivo evaluation in PSMA-positive xenograft models using PET and fluorescence imaging.
• First-in-human clinical studies to assess safety, biodistribution, and lesion detectability.

Main Results:

• The probe demonstrated good yield and stability, with rapid, specific tumor uptake and long retention in xenografts.
• Compared to [68Ga]Ga-PSMA-617, [68Ga]Ga-XY-PSMA-ICG showed significantly better tumor-to-background ratios at 60 min.
• Clinical studies confirmed good safety, favorable biodistribution, and excellent lesion detectability in prostate cancer patients.

Conclusions:

• [68Ga]Ga-XY-PSMA-ICG is a clinically translatable dual-modality probe for prostate cancer.
• It offers enhanced diagnostic capabilities for precise PCa management.
• The probe shows significant potential for further clinical application in prostate cancer imaging.