Local Production of the Alpha-Emitting Radioi-sotope Actinium 225 with Low Impurities for Targeted Alpha Ther-apy by a Compact Neutron Generator System

Abstract

Alpha-particle emitting radioisotope Actinium225 (225Ac) is of great interest for use in Targeted Alpha Therapy (TAT) treatments of e.g., brain tumors, bladder cancer, neuroendocrine tumors and leukemia. A suitable 225 Ac radioligand is also potentially resolutive for the treatment of advanced and metastatic Castration-Resistant Prostate Cancers (mCRPCs). The mCRPC has a mean survival rate of 9-36 months and encompasses a heterogeneous ample range of molecular cancer behavior with a high risk of progression. Global demand for the 225 Ac has spurred several production efforts including extraction from 233U, high energy protons or photon irradiation of 226Ra or spallation of 232Th by, at least, 100 MeV protons. Instead of using accelerators systems such as cyclotrons or LINACs, a Compact Neutron Generator (CNG) system has been developed. A 400kV-10 mA DC (D_7Li) CNG potentially able to produce substantial amount of 225Ac with low 227Ac impurities is here presented. Exploiting the high flux of 10 and 13 MeV energy neutrons generated by the (D_7Li) reactions to bombard a thin target layer of 226Ra, 225Ra/225Ac is produced via the 226Ra(n,2n)225Ra nuclear reaction. By irradiating a 5 mm thick 226Ra layer for 100 hours, about 11-13 mCi of 225Ac can be produced – corresponding to the TAT treatment of about 65 oncological patients – with an estimated 227Ac contamination of about one percent, which is below the acceptable limit for clinical use. This 225Ac production scheme by a suitable CNG should allow to adopt a local/regional approach avoiding the shipment costs of 225Ac. The aim of this paper is to inform the production chain of radioisotopes to be used in medical field and the medical community involved in the application of radiopharmaceuticals for the cure of cancer, that a new technology based on Compact Neutron Generators (CNG) is in a R&D phase and will allow to produce the necessary quantity of radioisotopes for clinical and research purpose. This will be essential in treatment advanced metastatic cancer as for instance the metastatic Castration – Resistant Prostate Cancer.