PRRT is Currently Used to Treat Prostate Cancer
131I-labeled prostate-specific membrane antigen (PSMA) ligands showed promise for prostate cancer therapy and were further developed to ”the?177Lu-PSMA” introduced in 2015.
PSMA is a transmembrane protein that is over-expressed in prostate cancer (PC) cells, and its expression increases progressively in higher-grade cancers such as metastatic castration-resistant prostate cancer (mCRPC) PC. Its benefits remain high even after multiple lines of therapy.
Radionuclide PSMA is a promising therapeutic approach for mCRPC patients for whom chemotherapy has been ineffective. Early reports show that?177Lu-PSMA is safe and effectively reduces the tumor burden. It has low toxicity and has become popular, with more than a thousand therapy cycles performed. Severe haematological side effects are rare. Organs at risk after treatment with?177Lu-PSMA, including the salivary glands and the kidneys. However, the radiation dose to bone marrow, spleen, and liver is below critical limits.
Currently, the two most frequently used PSMA ligands are PSMA-617 and PSMA-I&T (imaging and therapy), labeled with?177Lu. PSMA- targeting ligands using?225Ac maybe have an advantage compared to PSMA-targeting ligands using β particles.
Clinical studies using?225Ac-labeled PSMA-ligands (PSMA-617 or PSMA-I&T) have demonstrated remarkable therapeutic results recently. Data on treatment with?225Ac-PSMA-617 indicate an excellent effect on tumor control in both early and late-stage mCRPC.
A novel α particle treatment with a?227Th-PSMA has shown potency in in vitro studies and efficacy in xenograft models of prostate cancer. However, α particles have a more significant radiobiological effect on the organs at risk. Concerns have been raised about treatment-associated, mostly permanent xerostomia, frequently leading to treatment discontinuation in many patients. Combining α particles with β particle emitters is called “tandem therapy” and may reduce these significant adverse effects compared to using α particles alone.