Abstract No. 323 Hitting the Bull’s Eye: A Nanoscale PSMA-Targeted Ultrasound Contrast Agent (UCA) for Prostate Cancer Molecular Imaging

PSMA-Targeted Nanobubbles (PSMA-NB) are a promising clinical tool for increasing the accuracy of prostate biopsy in situations where multiparametric magnetic resonance imaging (mpMRI) is not available. PSMA-NB contrast-enhanced ultrasound (CEUS) allows for targeted biopsy, reducing the number of necessary samples and aiding in the reduction of complications associated with prostate biopsy. The significantly longer half-life of PSMA-NB enables more comprehensive evaluation by the physician. Furthermore, PSMA-NB allows for real-time molecular imaging of the prostate, which can greatly aid in the accurate diagnosis and management of prostate cancer. Our goal is to assess experimental PSMA-targeted nanobubbles (PSMA-NB) as a UCA for prostate cancer ultrasound molecular imaging in large animal models. Five sexually mature male New Zealand white rabbits and four male beagles were used in the study. Prostate cancer cells were inoculated into the prostate glands via US-guided injection. Multiparametric magnetic resonance imaging (mpMRI) and NB-based CEUS were performed to evaluate tumor growth. Clinically approved microbubble UCA (MB) was used as a control. The rabbits were imaged with a transabdominal approach (17 MHz), while the dogs were imaged with an 8 MHz transrectal end-fire probe. UCA was injected through peripheral vein access and was imaged for 15 minutes after injection. Time-intensity curves (TICs) were normalized for the baseline signal intensity and peak value, and decorrelation time (DT) and area under the curve (AUC) mapping was performed. At the end of the study, tumors were harvested for histopathology assessment. In the rabbit model, PSMA-NB showed a two times higher signal and longer half-life (contrast signal >10 min) than MB in early-stage tumors (< 75 mm3). PSMA-NB demonstrated slower wash-out on tumors than normal prostate, indicating contrast retention; no difference in wash-out was observed with MB. Differences were preserved in tumors outside the prostate. In the canine model, decorrelation time mapping of PSMA-NB clearly delineated tumor growth zones with high cellular activity confirmed by histopathology. Our study demonstrated that PSMA-NB has the potential to highlight tumor areas within the prostate gland in both rabbit and canine models of prostate cancer. NBs showed contrast retention and slower washout of PSMA-NB, enabling differentiation between tumor interest zones and normal prostate tissue. These findings suggest that PSMA-NB UCA could be a promising tool for prostate cancer diagnosis and treatment.