Abstract

Abstract Introduction: Prostatic cancer (PCa) is the second most prevalent disease in men globally. In 2020 it lead to >14 million new cases and >375,000 deaths worldwide. Despite numerous detection methods, detecting PCa reliably and non-invasively continues to be challenging. PCa malignant cells (MC) express VPAC (combined for Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Peptide) in high density. A VPAC specific PACAP analogues (Kd=3.1 × 10−8M) developed in our laboratory was conjugated with a fluorophore and named TP4303. The goal was to assess if TP4303 will image PCa-MC shed in voided urine and present severity of PCa as grade group (GG). Method: Consenting PCa patients (N=110) scheduled for radical prostatectomy provided voided urine. Urine was cyto-centrifuged. Cells on glass slide were fixed, incubated with TP4303, washed, treated with DAPI (4,6-diamidodino-2-phenylindole), cover slip placed and analyzed with Zeiss Axio Observer microscope, coupled with ZENN Microscopy software. The software determined percentage of PCa MC shed by each patient. The results were corroborated as per GG, determined by post-surgical histopathology and analyzed statistically. Results:TP4303 imaged PCa in all subjects. The percent MC shed in urine increased from 13.1±14.4% for GG1 to 25.3±21.07% for GG3 (p=0.05) to 50.5±26.7% for GG5 (p=0.002). Similarly, the fluorescence intensity increased from 43.8±2.2 for GG1 to 48.8±7.0 for GG3 (p=0.01) to 51.5±14.4 for GG5 (p=0.15). Conclusions: The data strongly suggests that TP4303 may not only detect PCa reliably and noninvasively, but may also predict the severity of PCa. Supported by NIH: NC5R01CA249921 Citation Format: Mathew L. Thakur, Vivek S. Tomar, Emma Dale, Leonard G. Gomella, Hector T. Navarro, Oleksandr Kolesnikov, Joon Yau Leong, Olivia Dahlgren, Edouard J. Trabulsi. Targeting genomic biomarker in voided urine for prostate cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1031.

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