Challenging production of Auger electron emitter platinum-195m via double-neutron capture activation of an iridium-193 target

Abstract

Targeted Auger electron (AE) therapy exhibits great potency against small tumors and metastatic sites, which to date have no effective therapeutic options. However, the development of AE-based therapy is significantly limited due to the low availability of the most promising radionuclides, being the consequence of the poor cognition of relevant nuclear pathways and insufficient accessibility of highly enriched target materials and specific infrastructure. Therefore, the development and investigation approaches to overcome this limitation are highly complex and challenging. In the present paper, as a second group worldwide, we perform experimental evaluation of double-neutron capture of a <sup>195m</sup>Pt production – radionuclide showing the most favourable characteristics for targeted Auger electron therapy. For this purpose we investigated two-step iridium target activation via <sup>193</sup>Ir(n,γ)<sup>194</sup>Ir(n,γ)<sup>195m</sup>Ir(β-)➝<sup>195m</sup>Pt. In presenting the current state of knowledge of identified production methods of this radionuclide, we highlight the limitations and challenges of cyclotron- and reactor-based approaches. With theoretical calculations followed by short-time irradiation with thermal neutron flux, we describe numerous nuclear and chemical difficulties associated with an investigated nuclear pathway. Obtained results reveal that research and commercial application of this method is significantly hindered or even impossible at the current state of knowledge. We point out the most critical limitations which need to be addressed for further consideration of the mentioned strategy. Therefore, <sup>195m</sup>Pt application for targeted Auger therapy still remains challenging and requires efforts to overcome the limitations.