The importance of 177Lu-PSMA in the treatment of castration-resistant prostate cancer

Abstract

The importance of 177Lu-PSMA in the treatment of castrationresistant prostate cancer There are some treatment options for metastatic and castration-resistant prostate cancer, and there is no single standardized treatment protocol today. In this group of patients, the chance of success in the treatment increased with the introduction of abiraterone, enzyalutamide/ apalutamide, taxane chemotherapy (docetaxel, cabazitaxel) and immunotherapy (ipilimumab, sunitinib, cabozantinib, or xofigo). Although there was an increase in both disease-free and overall survival, resistance to these drugs developed within 1-2 years. Therefore, the search for new treatments has continued [1–3]. In recent years, 223radium and 177lutetium (177Lu) prostatespecific membrane antigen (PSMA) have been shown to provide effective treatment of metastatic and castration-resistant prostate cancer with the application of radiopharmaceuticals containing ionizing radiation. The use of 177Lu-PSMA treatment, which is a radionuclide treatment, is increasing day by day [4–6]. PSMA is a transmembrane glycoprotein with enzyme functions in the cell. It takes part in cell migration, cell survival and proliferation. Although healthy prostate epithelial cells have low expression, prostate cancer can be found in rates up to 1,000-times. This has made the PSMA molecule a target for radiopharmaceuticals in the dia gnosis and treatment of prostate cancer. First of all, radiopharmaceuticals using antibody-mediated carrier molecules have been developed and used limitedly for imaging and treatment purposes. Later, small molecular weight molecules developed from inhibitors of the enzyme component of the molecule were marked with radionuclides such as 68Ga, 18F, 44Sc, 177Lu, 225Ac, 211At and many treatment and imaging radiopharmaceuticals developed in this way quickly entered clinical use and became widespread. 177Lu was the most preferred among these. It is a radionuclide with a half-life of 6.64 days and emits beta and gamma rays. While beta rays from 177Lu decay are used to kill tumor cells, gamma rays are used for patient imaging and dosimetry studies [1–3,7–8]. It is administered intravenously to the patient in the form of 177Lu-PSMA-617 or 177Lu-PSMA I&T radiopharmaceutical. This radiopharmaceutical is collected intensely in the structure and the tumor is treated through the beta rays emitted. Standard activity after the application is 3–8 GBq. This treatment is repeated 4or 6-times with an average interval of 2 months. With the internal dosimetry calculations to be made before or after the treatment, it is possible to select patients with higher doses or those who may develop toxicity in fixed dose protocols, albeit few [3,4,8,9]. Due to the distribution of radiation within the body; critical organs sensitive to radiation such as kidney, bone marrow and liver take the same dose. These critical organ doses are one of the most important factors affecting the number of treatments. To monitor these side effects, complete blood count, serum creatinine level, alanine aminotransferase, aspartate aminotransferase levels are measured before and after the application of 177Lu-PSMA treatment. Treatment response evaluation is basically performed by monitoring serum alkaline phosphatase, serum prostate specific antigen (PSA) level and PSMA positron emission tomographic (PET) imaging. Although it is generally accepted that PSA level and PSMA PET should be performed after at least two cycles of treatment, there is no consensus about when to evaluate the treatment [1–4]. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.