March 2022

Prostate cancer is one of the most commonly diagnosed cancers, affecting 1 out of 8 men in the United States between the ages of 65-74. Symptoms of prostate cancer include problems with urination, blood in urine, bone and back pain, numbness in legs, loss of bladder and bowel control, weight loss, and loss of appetite. Although early stages of this disease can be successfully treated with therapy and disease progression can be actively monitored by physicians, advanced prostate cancer remains incurable and fatal.

Prostate cancer occurs when the cells in the reproductive gland that produce seminal fluid either grow out of control or begin to die more slowly than usual [1]. An essential biomarker for prostate cancer cells is the overexpression of surface prostate-specific membrane antigen (PSMA), a transmembrane glutamate carboxypeptidase.  

In 2021, VISION researchers released a study that detailed the results of a large Phase 3 clinical trial that sought to demonstrate the effect of the radiopharmaceutical drug Lu-PSMA-617 (Pluvicto) on patients with metastatic castrate-resistant prostate cancer. The study found that Lu-PSMA-617 prolonged imaging-based progression-free survival and overall survival in participants when added along to standard treatments when compared to those who received only standard therapies [2]. This emerging class of drugs promises a safe and effective targeted approach to destroy cancer cells that are resistant to other therapies.  

The drug mechanism of radionuclides consists of two components: a drug and a radioactive particle. In Lu-PSMA-617, the small-molecule drug is PSMA-617, which serves as the delivery vehicle that binds to the PSMA protein and is then engulfed by the cancer cell. The cell then becomes exposed to the radioactive particle, Lutetium-177, that emits toxic levels of beta-ray radiation, effectively killing the cell. Lu-177 is regarded as the radiometal of choice for radionuclide therapy due to its commercial availability, compatibility with targeting agents (t1/2 = 6.7 days), and clinical success [3]. 

This month, the FDA approved the use of Lu-PSMA-617 to treat patients that have metastatic prostate cancer that is hormone-resistant, has significantly progressed despite receiving standard treatment of care, and whose tumors overproduce the PSMA protein. In order to be a candidate of this targeted radionuclide therapy, the FDA regulates that PSMA-positive radioactive tracers, like gallium Ga 68 gozetotide (Locametz), be used during PET imaging to detect lesions based on elevated PSA levels before initiating treatment [4].

References:

[1] Merriel, S., Funston, G., & Hamilton, W. (2018). Prostate Cancer in Primary Care. Advances in therapy, 35(9), 1285–1294. https://doi.org/10.1007/s12325-018-0766-1

[2] Sartor, O., de Bono, J., Chi, K. N., Fizazi, K., Herrmann, K., Rahbar, K., Tagawa, S. T., Nordquist, L. T., Vaishampayan, N., El-Haddad, G., Park, C. H., Beer, T. M., Armour, A., Pérez-Contreras, W. J., DeSilvio, M., Kpamegan, E., Gericke, G., Messmann, R. A., Morris, M. J., Krause, B. J., VISION Investigators (2021). Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. The New England journal of medicine, 385(12), 1091–1103. https://doi.org/10.1056/NEJMoa2107322

[3] Rinne, S.S., Vorobyeva, A (2021). Radiometals—Chemistry and radiolabeling. In: Reference Module in Biomedical Sciences [Internet]. Elsevier. Available from: https://www.sciencedirect.com/science/article/pii/B9780128229606000442

[4] FDA approves Pluvicto for metastatic castration-resistant prostate cancer | FDA. (n.d.). U.S. Food and Drug Administration; FDA. Retrieved March 23, 2022, from  https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer