Development of Heterobivalent Theranostic Probes Having High Affinity/Selectivity for the GRPR/PSMA.

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Chemistry
• Molecular Imaging

Background:

• Gastrin-releasing peptide receptor (GRPR) and prostate-specific membrane antigen (PSMA) are key targets in prostate cancer.
• Development of targeted radiopharmaceuticals is crucial for accurate cancer imaging and therapy.

Purpose of the Study:

• To develop and evaluate novel heterobivalent radiotracers targeting both GRPR and PSMA.
• To assess the in vitro and in vivo performance of these radiotracers for potential clinical applications.

Main Methods:

• Synthesis and characterization of heterobivalent radiotracers [DUPA-6-Ahx-([111In]In-DO3A)-8-Aoc-BBN ANT] and [DUPA-6-Ahx-([177Lu]Lu-DO3A)-8-Aoc-BBN ANT].
• In vitro binding affinity assays using PC-3 and LNCaP cell membranes.
• In vivo biodistribution and micro-single-photon emission computed tomography (microSPECT) imaging in tumor-bearing mice.

Main Results:

• Radiotracers demonstrated high binding affinity for GRPR and PSMA.
• Favorable pharmacokinetic and excretion profiles observed.
• High tumor uptake (4.74-7.51%ID/g at 1h) and retention in PC-3 or PC-3 PIP tumor models.
• MicroSPECT imaging confirmed high tumor accumulation with minimal off-target tissue uptake.

Conclusions:

• The developed heterobivalent radiotracers exhibit excellent selectivity and specificity for GRPR/PSMA-expressing cells.
• These radiotracers show promising potential for diagnostic imaging and targeted radionuclide therapy in prostate cancer.