Actinium-225 in Targeted Alpha Therapy

Abstract

The utilization of actinium-225 (²²⁵Ac) radionuclides in targeted alpha therapy for cancer was initially outlined in 1993. Over the past two decades, substantial research has been conducted, encompassing the establishment of ²²⁵Ac production methods, various preclinical investigations, and several clinical studies. Currently, there is a growing number of compounds labeled with ²²⁵Ac that are being developed and tested in clinical trials. In response to the increasing demand for this nuclide, production facilities are either being built or have already been established. This article offers a concise summary of the present state of clinical advancements in compounds labeled with ²²⁵Ac. It outlines various processes involved in the production and purification of ²²⁵Ac to cater to the growing demand for this radionuclide. The article examines the merits and drawbacks of different procedures, delves into preclinical trials, and discusses ongoing clinical trials.

Keywords: Actinium-225; alpha emitter; nuclear medicine; oncology; targeted alpha therapy.

Figure 1

Decay scheme of actinium-225

Figure 2

Daily production of actinium-225 through different production methods across various laboratories

Figure 3

A 79-year-old metastatic castration-resistant prostate cancer patient (patient 11) with lymphatic and bone metastases. The patient received two cycles of 177Lu-PSMA RLT (cumulative activity, 10.5 GBq) after the failure of docetaxel and showed an initial response. However, disease progression was observed in January 2019 after two additional 177Lu-PSMA RLT cycles (cumulative activity, 12 GBq), and the patient was admitted for actinium-225-PSMA-I and T TAT. PSA follow-up and PSMA PET showed impressive response after two cycles (cumulative activity, 13.4 MBq). Unfortunately, the patient developed grade 3 leukocytopenia, and TAT could not be continued. Disease progression was observed in November 2019 after best supportive care (BSC)[49]