A Preclinical Study of a PSMA Ligand-Based Dual-Modality Probe for Radical Prostatectomy.

Area of Science:

• Oncology
• Medical Imaging
• Radiochemistry

Background:

• Prostate-specific membrane antigen (PSMA) is a key target in prostate cancer (PCa).
• Dual-modality imaging probes combine radionuclide and near-infrared fluorescence (NIRF) for enhanced tumor visualization.
• PSMA-targeted probes improve surgical guidance in PCa by offering complementary preoperative and intraoperative imaging.

Purpose of the Study:

• To develop a novel dual-labeled PSMA probe ([68Ga]Ga-PSMA-DF) integrating radioactive and fluorescent properties.
• To achieve precise tumor delineation during radical prostatectomy (RP) using this dual-modality probe.
• To evaluate the in vitro and in vivo performance and safety of the novel probe.

Main Methods:

• Synthesis of a high-affinity PSMA-targeted fluorescent probe (PSMA-DF) via solid-phase synthesis.
• Radiolabeling of PSMA-DF with Gallium-68 ([68Ga]) to create the dual-modal probe [68Ga]Ga-PSMA-DF.
• In vitro and in vivo evaluation in PSMA-positive (22Rv1) and PSMA-negative (PC-3) PCa cell lines and xenograft models, using micro-PET/CT and NIRF imaging.

Main Results:

• Successful synthesis of high-purity PSMA-DF with excellent optical properties and subsequent generation of [68Ga]Ga-PSMA-DF.
• High specific uptake of [68Ga]Ga-PSMA-DF in PSMA-positive 22Rv1 cells and xenografts, with minimal uptake in PC-3 cells.
• Effective tumor visualization in vivo via micro-PET/CT and NIRF imaging, demonstrating high tumor accumulation and tumor-to-background ratios.

Conclusions:

• The dual-modality probe [68Ga]Ga-PSMA-DF exhibits high and specific uptake in preclinical PCa models.
• This probe holds significant potential as a dual-tracer for both PET/CT imaging and intraoperative fluorescence guidance in PCa surgery.
• Further validation is warranted to translate these findings into clinical practice for improved surgical outcomes.