[^99mTc]Tc-HYNIC-RM2: A potential SPECT probe targeting GRPR expression in prostate cancers

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Chemistry
• Oncology

Background:

• Gastrin-releasing peptide receptors (GRPR) are overexpressed in prostate cancer, making them a target for imaging and staging.
• Previous research utilized gallium-68 labeled RM2 peptide, necessitating the development of alternative radiotracers for Single Photon Emission Computed Tomography (SPECT) imaging.

Purpose of the Study:

• To synthesize and evaluate a novel 99mTc-labeled HYNIC-RM2 peptide conjugate for SPECT imaging of GRPR-positive prostate cancer.
• To assess the in vitro and in vivo performance of 99mTc-HYNIC-RM2 in preclinical models.

Main Methods:

• HYNIC-RM2 peptide was synthesized using Fmoc solid-phase strategy and radiolabeled with 99mTc.
• In vitro studies were conducted on GRPR-positive PC3 cells.
• Metabolic stability, biodistribution, and SPECT/CT imaging studies were performed in SCID mice bearing PC3 xenografts, with and without the neutral endopeptidase inhibitor phosphoramidon (PA).

Main Results:

• 99mTc-HYNIC-RM2 demonstrated high binding affinity (Kd = 1.83 ± 0.31 nM).
• Co-administration of PA significantly enhanced metabolic stability (90% intact at 15 min p.i.) and tumor uptake (14.24 ± 0.76 %ID/g at 1h).
• SPECT/CT imaging clearly visualized PC3 xenografts, with uptake specificity confirmed by blocking studies.

Conclusions:

• 99mTc-HYNIC-RM2 exhibits promising characteristics for GRPR-targeted SPECT imaging of prostate cancer.
• The results support further investigation of 99mTc-HYNIC-RM2 as a diagnostic agent for GRPR-positive tumors.