In-house cyclotron production of high-purity Tc-99m and Tc-99m radiopharmaceuticals

Abstract

In the last years, the technology for producing the important medical radionuclide technetium-99m by cyclotrons has become sufficiently mature to justify its introduction as an alternative source of the starting precursor [^99mTc][TcO₄]^- ubiquitously employed for the production of ^99mTc-radiopharmaceuticals in hospitals. These technologies make use almost exclusively of the nuclear reaction ¹⁰⁰Mo(p,2n)^99mTc that allows direct production of Tc-99m. In this study, it is conjectured that this alternative production route will not replace the current supply chain based on the distribution of ⁹⁹Mo/^99mTc generators, but could become a convenient emergency source of Tc-99m only for in-house hospitals equipped with a conventional, low-energy, medical cyclotron. On this ground, an outline of the essential steps that should be implemented for setting up a hospital radiopharmacy aimed at the occasional production of Tc-99m by a small cyclotron is discussed. These include (1) target production, (2) irradiation conditions, (3) separation/purification procedures, (4) terminal sterilization, (5) quality control, and (6) Mo-100 recovery. To address these issues, a comprehensive technology for cyclotron-production of Tc-99m, developed at the Legnaro National Laboratories of the Italian National Institute of Nuclear Physics (LNL-INFN), will be used as a reference example.

Keywords: (99m)Tc-radiopharmaceuticals; Cyclotron; European Pharmacopoeia; Generator; Hospital radiopharmacy; Molybdenum-100; SPECT; Technetium-99m.