VAPC-1 receptor is well known receptor associated with cancer cell growth and angiogenesis by stimulation of the EGFR and HER 2 pathways. VPAC-1 has been noted to be overexpressed in various malignancies, bladder and prostate cancer showing close to 100% over-expression. In preliminary studies, the overexpression of VAPC-1 has been found before any histological evidence of neoplasia in prostate cancer tissue, suggesting its use in the diagnosis of prostate cancer. The speaker reports the ability to detect prostate cancer cells in the urine in patients with prostate cancer using VAPC-1 as a diagnostic target. The receptor is not overexpressed in patients with BPH noting is specificity for malignant conditions. The clinical implications for the use of VPAC-1 for the detection of prostate cancer remains to be validated as well as its association with clinical significant versus clinical insignificant disease.
Dr. Thakur’s laboratory has developed a PET radio-ligand targeting the VAPC-1 receptor. The ligand is a copper based ligand currently is known as 64Cu-TP3805. The ligand has demonstrated high sensitivity to prostate cancer, detecting the site of prostate cancer in patients undergoing a radical prostatectomy. Its association with Gleason grade has not been validated but studies are on-going attempting to merge the radio-ligand with mpMRI targeted biopsies. The radio ligand has also been tested in patients with metastatic disease noting comparable sensitivity to 18F-NaF PET/CT scans. Importantly the radio-ligand has 100% hepatobiliary excretion making it an excellent candidate for GU based studies. No study validating its use in the clinical setting has been performed and the tracer remains experimental.
Lastly, there is significant excitement about the use of the agent in theranostics treatments given its cancer specificity compared to other available agents. Dr. Thakur points out that PSMA agents are heavily concentrated in the salivary glands and in the cornea which may cause xerostomia (dry mouth) or cataracts in patients in whom PSMA targeted treatments are used. Cu-TP3805 demonstrates minimal concentration in benign tissues which will advantageous for reduction of side effects.
In summary, VAPC-1 appears to be an exciting target for prostate cancer imaging. Its use appears to be wide, from a potential urinary marker to its use in theranostic agents. Early phase trials are still pending but they are awaited with excitement.
Presented by: Madhukar (Mathew) Thakur PhD, Professor of Radiology at Jefferson Hospital in Philadelphia, PA
Written by: Andres F. Correa, Society of Urologic Oncology Fellow,Fox Chase Cancer Center-Temple Health, Philadelphia, PA at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC