Large-Scale Production of ^119mTe and ¹¹⁹Sb for Radiopharmaceutical Applications

Abstract

Radionuclides find widespread use in medical technologies for treating and diagnosing disease. Among successful and emerging radiotherapeutics, 119 Sb has unique potential in targeted therapeutic applications for low-energy electron-emitting isotopes. Unfortunately, developing 119 Sb-based drugs has been slow in comparison to other radionuclides, primarily due to limited accessibility. Herein is a production method that overcomes this challenge and expands the available time for large-scale distribution and use. Our approach exploits high flux and fluence from high-energy proton sources to produce longer lived 119m Te. This parent isotope slowly decays to 119 Sb, which in turn provides access to 119 Sb for longer time periods (in comparison to direct 119 Sb production routes). We contribute the target design, irradiation conditions, and a rapid procedure for isolating the 119m Te/ 119 Sb pair. To guide process development and to understand why the procedure was successful, we characterized the Te/Sb separation using Te and Sb K-edge X-ray absorption spectroscopy. The procedure provides low-volume aqueous solutions that have high 119m Te—and consequently 119 Sb—specific activity in a chemically pure form. This procedure has been demonstrated at large-scale (production-sized, Ci quantities), and the product has potential to meet stringent Food and Drug Administration requirements for a 119m Te/ 119 Sb active pharmaceutical ingredient.

Spontaneous Chelation‐Driven Reduction of the Neptunyl Cation in Aqueous Solution

“…XANES spectroscopy can be used to determine metal oxidation states in solution, which is generally done by comparing spectral characteristics, such as edge energy to known standards for a given element . XANES spectra at the Np L III ‐edge of all four Np‐343 ligand complexes are shown in Figure , and these results highlight the challenge in using XANES to determine Np oxidation states.…”

The Paradox of Using Radionuclides To Treat Disease

“…Recently, Kozimor and co-workers have discovered a new way for the large-scale isolation and production of 119 Sb that may enable targeted radiotherapeutic applications (see Figure 1). 2 This radionuclide shows special promise of potentially delivering lethal doses of radiation to targeted diseased cells, reducing side-effects by leaving adjacent healthy tissue unharmed.…”

“…The latter will be used in targeted radiotherapy. Reprinted with permission from ref (2). Copyright 2019 American Chemical Society.…”

“…The new 119 Sb production and separation method described by Kozimor and co-workers represents an exciting leap forward for targeted radiotherapeutic uses of Auger-emitting isotopes. 2 It offers the opportunity to greatly increase access to 119 Sb beyond the relatively limited number of medical institutions that have colocated 119 Sb production sites. The team demonstrated that large quantities of 119 Sb could be generated by proton irradiation of natural abundance Sb at high energy proton sources, i.e., the Isotope Production Facility (IPF) at the Los Alamos Neutron Science Center (LANSCE) at Los Alamos National Laboratory (LANL) and the Brookhaven Linac Isotope Producer (BLIP) at Brookhaven National Laboratory.…”

“…Recently, Kozimor and co-workers have discovered a new way for the large-scale isolation and production of 119 Sb that may enable targeted radiotherapeutic applications (see Figure ). This radionuclide shows special promise of potentially delivering lethal doses of radiation to targeted diseased cells, reducing side-effects by leaving adjacent healthy tissue unharmed. This radionuclide shows special promise of potentially delivering lethal doses of radiation to targeted diseased cells, reducing side-effects by leaving adjacent healthy tissue unharmed…”