VPAC1 targeted detection of genitourinary cancer: a urinary assay

Objectives Genitourinary cancers, such as prostate (CaP) and bladder urothelial (BUC) cancer, are the most common malignancies, yet their non-invasive diagnosis remains challenging. In recent years, detecting circulating tumor cells in peripheral blood has drawn a considerable attention to assess the primary disease, as well as to determine effectiveness of therapy and predict recurrence of disease. These techniques are complex and are not yet widely used in routine clinical practice. On their cells, both diseases express VPAC1 receptors in high density. The goal is to target VPAC1 for detection of shed cancer cells (SCC) in voided urine using TP4303, a VPAC1 specific biomolecule linked with a near infrared fluorophore.

Methods Urine samples (n=203) were collected from normal volunteers (n=53, M=22, F=31) and from patients with CaP (n=76), BUC (n=35, M=25, F=10), benign prostatic hyperplasia (BPH, n=4), and with other non-oncologic complaints (n=35, M=14, F=21). The urine was cytospun, cells were fixed, incubated with TP4303 (Ex=633nm, Em=754nm), washed, and cell nuclei were stained with DAPI (Ex=350nm, Em=470nm). Slides were read using a confocal microscope. The protocol was IRB exempt as no health record was required to be collected.

Results 74/76 CaP had SCC (97.4%), one was negative for SCC (1.3%), and one was technically unclear. For BUC, 33/35 (94.3%) had SCC, one was negative (2.8%), and one was technically unclear (2.8%). None of the 4 BPH had SCC (100%). In 53 normals, 11 had SCC (20.7%), 32 were negative (60.4%), and 10 were technically unclear (18.8%). In miscellaneous 35 subjects, 19 (54.3%) had SCC, 13 (37.1%) were normal, and 3 (8.6%) were technically unclear.

Conclusions The method is simple, noninvasive, rapid, and detects SCC with a high sensitivity in voided urine of patients with CaP and BUC.

Research Support NIH CA157372-02 and NuView Inc. (MLT)