PET Imaging of New Target PARP in Prostate Cancer.

Background/

Objectives

Poly (ADP-ribose) polymerase (PARP), particularly PARP-1, is overexpressed in prostate cancer and linked to poor prognosis. PARP inhibitors show efficacy in homologous recombination deficiency (HRD)-positive tumors, but 30-70% of patients develop resistance, often due to low PARP expression. Tissue biopsies have limitations in assessing PARP levels, highlighting the need for noninvasive imaging tools. This study aimed to develop a novel [68Ga]Ga-PARP-targeted radiotracer for prostate cancer visualization and therapy monitoring, with potential implications for targeted radionuclide therapy.

Methods

PET/CT imaging was conducted in 22RV1 prostate cancer xenograft-bearing mice using the [68Ga]Ga-FL9-7 probe. Imaging was performed at 1, 2, and 3 h post-injection. Standardized uptake values (SUV) were quantified to evaluate tumor and organ uptake, and tumor-to-normal tissue (T/NT) contrast ratios were calculated.

Results

[68Ga]Ga-FL9-7 rapidly accumulated in tumors, with optimal imaging contrast achieved at 3 h post-injection. Normal organ uptake (e.g., kidneys) peaked at 1 h and subsequently declined, while tumor uptake increased over time. This differential clearance and retention resulted in the highest T/NT ratio at the 3 h time point.

Conclusions

The [68Ga]Ga-FL9-7 probe enables effective noninvasive visualization of PARP-1 expression in prostate cancer, demonstrating clinical potential for tumor localization and monitoring of PARP-targeted therapies. This work also lays the groundwork for further development of PARP-targeted radionuclide therapy strategies.