The advent of Astatine-211 in targeted radionuclide therapy in prostate cancer: will it come to true fruition?

Abstract

With the growth and surge of prostate cancer theranostics globally, multiple targeted radionuclide therapy (TRT) agents have been utilized to aim to provide a tumoricidal effect to patients who would benefit from TRT. Despite the fact that approved isotopes such as Strontium-89, Samarium-153 and Radium-223 exist, Lutetium-177 prostate specific membrane antigen (PSMA) has revolutionized the impact of radioligand therapy (RLT) in this domain. Key defining clinical trials such as the VISION, TheraP and PSMAfore trials have given clear evidence of the benefit of PSMA RLT in the treatment landscape of metastatic castrate resistant prostate cancer. A number of other radioisotopes in the PSMA RLT domain have also more recently come into the field, notably Terbium-161, Copper- 67 and Iodine-131. Targeted Alpha Therapy (TAT) has grown significantly as well over the last few years owing to physical properties of its high linear energy transfer and DNA damage provided by alpha particles in comparison to beta particles. Actinium-225 PSMA based TAT has formed the basis of prostate cancer theranostics since its initial application, however, many other alpha isotopes are being explored owing to some of the side effects that Actinium-225 presents. Astatine-211, owing to its shorter half-life, has become a more attractive option for its potential utilization in prostate cancer theranostics. Whilst there is preclinical work detailing its efficacy in suppressing tumor growth and limited toxicity profiles, translation into humans is still in its infancy and requires further exploration. A number of clinical trials have utilized Astatine-211 in other malignancies with virtually no work related to prostate cancer. Moreover, the logistics and infrastructure required to support global efforts to make Astatine-211 more readily available should be high on the agenda as well. This narrative review of the literature aims to showcase the current status of Astatine-211 efforts in prostate cancer care with available data (including clinical trials).