A Review of 177Lutetium-PSMA and 225Actinium-PSMA as Emerging Theranostic Agents in Prostate Cancer

Abstract

The development of prostate-specific membrane antigen (PSMA) ligands labeled with radionuclides is a ground-breaking achievement in the management of prostate cancer. With the increasing use of 68 Gallium-PSMA and 18 F-DCFPyL (Pylarify) and their approval by the Food and Drug Administration (FDA), other PSMA agents and their unique characteristics are also being studied. Two other PSMA agents, namely 177 Lutetium-PSMA ( 177 Lu-PSMA) and 225 Actinium-PSMA ( 225 Ac-PSMA), are currently drawing the researcher's attention mainly due to their theranostic importance. Studies focusing on the essential characteristics of these two emerging radiotracers are relatively lacking. Hence, this review article, beginning with a brief introduction, intends to provide insights on the mechanism, efficacy, adverse effects, usefulness, including theranostic implications, and limitations of these two emerging PSMA agents. The 177 Lu-PSMA is commercially accessible, is well tolerated, and has been found to lower prostate-specific antigen (PSA) levels while improving patients' quality of life. It also reduces pain and the requirement for analgesics and is safe for advanced diseases. However, despite its potential advantages, around one-third of patients do not respond satisfactorily to this costly treatment; it is still challenging to personalize this therapy and predict its outcome. Similarly, 225 Ac is compatible with antibody-based targeting vectors, releasing four extremely hazardous high-energy emissions with a longer half-life of 10 days. It has made 225 Ac-PSMA therapy useful for tumors resistant to standard treatments, with a better response than 177 Lu-PSMA. Dosimetry studies show a good biochemical response without toxicity in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). However, it can potentially cause significant damage to healthy tissues if not retained at the tumor site. Encapsulating radionuclides in a nano-carrier, hastening the absorption by tumor cells, and local delivery might all help reduce the harmful consequences. Both have advantages and disadvantages. The choice of PSMA agents may rely on desired qualities, cost, and convenience, among other factors. Further research is warranted in order to better understand their ideal use in clinical settings.

Fibroblast Activation Protein Inhibitor (FAPI)-Based Theranostics—Where We Are at and Where We Are Heading: A Systematic Review

“…To this day FAPI α-therapy has only been reported in preclinical settings in mice with 225-Actinium ( 225 Ac-FAPI-04) [ 72 ]. 225 Ac is a pure α emitter that has seen application in prostate and neuroendocrine cancers [ 73 , 74 , 75 ]. This would require FAPI ligands with a long retention time in tumor lesions to make up for the long half-life of 225 Ac (9920 days) as well as 177 Lu (66,443 days).…”

The Application of Radiolabeled Targeted Molecular Probes for the Diagnosis and Treatment of Prostate Cancer

“…2 ). Additionally, [ 225 Ac]PSMA treatment can benefit patients with mCRPC who has developed diffuse red bone marrow infiltration and fail to respond to other therapies [ 68 69 ]. Although, xerostomia is one of the adverse effects of [ 225 Ac]PSMA treatment , the treatment is generally tolerated by the patients, and the incidence of xerostomia is reduced by applying ice [ 70 71 ].…”

Nanoparticle-Based Radioconjugates for Targeted Imaging and Therapy of Prostate Cancer

“…Radiotherapy with α-emitting radionuclides seems to be a better alternative to this based on β − particles because α particles deposit their whole energy within a few cell diameters (<100 µm), efficiently inducing DNA damage [ 25 ]. However, one of the most important obstacles associated with α-emitting radionuclides is the liberation of the recoiled daughter radionuclides rising during decay, which allows them to freely migrate in the body, causing significant toxicity to healthy tissues and decreasing the therapeutic dose delivered to the tumour [ 26 , 27 ]. Encapsulation of radionuclides in tumour-targeting NPs may assist in overcoming problems associated with the harmful consequences of α-radionuclide therapy.…”