Lutetium ¹⁷⁷ PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Abstract

Prostate‐specific membrane antigen (PSMA) is a receptor on the surface of prostate cancer cells that is revolutionising the way we image and treat men with prostate cancer. New small molecule peptides with high‐binding affinity for the PSMA receptor have allowed high quality, highly specific PET imaging, in addition to the development of targeted radionuclide therapy for men with prostate cancer. This targeted therapy for prostate cancer has, to date, predominately used Lutetium 177 (Lu) labelled PSMA peptides. Early clinical studies evaluating the safety and efficacy of Lu PSMA therapy have demonstrated promising results with a significant proportion of men with metastatic prostate cancer, who have already failed other therapies, responding clinically to Lu PSMA. This review discusses the practical issues of administering Lu PSMA, and gives an overview of the findings from currently published trials in regards to treatment response rates, expected toxicities and safety.

Effect of External Cooling on 177Lu-PSMA Uptake by the Parotid Glands

“…Its physical half-life is 8.07 d, and the electrons penetrate soft tissue to a depth of about 1 mm, with a maximum of 2.4 mm (37)(38)(39). 177 Lu is a medium-energy b-emitter (490 keV) with a maximum energy of 0.5 MeV, a mean range of 0.7 mm and maximum range of 2.1 mm in soft tissue, and a half-life of 6.7 d (40). Although these properties are relatively similar for both radioactive isotopes, 177 Lu-PSMA uptake in the salivary glands is very high, with a transmembrane receptor-binding mechanism.…”

Preclinical assessment of 68Ga‐PSMA‐617 entrapped in a microemulsion delivery system for applications in prostate cancer PET/CT imaging

“…This means that radiation dose is delivered to these organs when [ 68 Ga]Ga‐PSMA‐617 or [ 177 Lu]Lu‐PSMA‐617 are used for radionuclide targeting or therapy. This has an effect on the side effect profile and safe dose that can be delivered without causing damage to nontarget tissue . In this study, therefore, [ 68 Ga]Ga‐PSMA‐617 was used as an imaging tool to evaluate the effect of ME on PSMA biodistribution with eventual future application for [ 177 Lu]Lu‐PSMA‐617.…”

Targeted Gold Nanocluster‐Enhanced Radiotherapy of Prostate Cancer

“…It is not secreted and is membrane bound, making it an attractive extracellular target for therapeutic probes for prostate cancer . In clinical studies, Lutetium 177 (Lu) labeled PSMA peptides have already proved to be effective in targeted radionuclide therapy of prostate cancer . Recently, we have developed a high‐affinity PSMA targeting ligand (PSMA‐1) and demonstrated its use in prostate cancer imaging and photodynamic therapy .…”