Radiopharmaceutical chemistry of targeted radiotherapeutics, part 4: Strategies for At labeling at high activities and radiation doses of 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-[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 At after distillation, a process referred to as At stabilization, on At chemistry after exposure to high radiation doses.

METHODS

High performance liquid chromatography was used to evaluate the distribution of 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 At timeactivity combinations under conditions with/without 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 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 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 At is a promising strategy for countering the deleterious effects of radiolysis on At chemistry.

ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE

This strategy could facilitate the ability to perform At labeling at sites remote from its production and at the high activity levels required for clinical applications.