Radiopharmaceutical chemistry of targeted radiotherapeutics, part 4: Strategies for 211 At labeling at high activities and radiation doses of 211 At α-particles.

INTRODUCTION: Alpha particles are radiation of high energy and short range, properties that can lead to radiolysis-mediated complications in labeling chemistry at the high radioactivity levels required for clinical application. In previous papers in this series, we have shown that radiation dose has a profound effect on the astatine species that are present in the labeling reaction and their suitability for the synthesis of N-succinimidyl 3-[211 At]astatobenzoate. The purpose of this study was to evaluate the effects of adding N-chlorosuccinimide (NCS) to the methanol solution used for initial isolation of 211 At after distillation, a process referred to as 211 At stabilization, on 211 At chemistry after exposure to high radiation doses.

METHODS: High performance liquid chromatography was used to evaluate the distribution of 211 At species present in methanol in the 500-65,000Gy radiation dose range and the synthesis of SAB from N-succinimidyl 3-(tri-n-butylstannyl)benzoate in the 500-120,000Gy radiation dose range using different 211 At timeactivity combinations under conditions with/without 211 At stabilization.

RESULTS: In the absence of NCS stabilization, a reduced form of astatine, At(2), increased with increasing radiation dose, accounting for about half the total activity by about 15,000Gy, while with stabilization, At(2) accounted for <10% of 211 At activity even at doses >60,000Gy. SAB yields without stabilization rapidly declined with increasing dose, falling to ~20% at about 5000Gy while with stabilization, yields >80% were obtained with 211 At solutions stored for more than 23h and receiving radiation doses >100,000Gy.

CONCLUSIONS: Adding NCS to the methanol solution used for initial isolation of 211 At is a promising strategy for countering the deleterious effects of radiolysis on 211 At chemistry.

ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: This strategy could facilitate the ability to perform 211 At labeling at sites remote from its production and at the high activity levels required for clinical applications.