Abstract

The high in vivo stability of 2,2-dihydroxymethyl-3-[¹⁸F]fluoropropyl-2-nitroimidazole ([¹⁸F]DiFA) prompted us to evaluate neopentyl as a scaffold to prepare a radiotheranostic system with radioiodine and astatine. Three DiFA analogues with one, two, or without a hydroxyl group were synthesized. While all ¹²⁵I-labeled compounds remained stable against nucleophilic substitution, only a ¹²⁵I-labeled neopentyl glycol was stable against cytochrome P450 (CYP)-mediated metabolism and showed high stability against in vivo deiodination. ²¹¹At-labeled neopentyl glycol also remained stable against both nucleophilic substitution and CYP-mediated metabolism. ²¹¹At-labeled neopentyl glycol showed the biodistribution profiles similar to those of its radioiodinated counterpart in contrast to the ¹²⁵I/²¹¹At-labeled benzoate pair. The urine analyses confirmed that ²¹¹At-labeled neopentyl glycol was excreted in the urine as a glucuronide conjugate with the absence of free [²¹¹At]At^–. These findings indicate that neopentyl glycol would constitute a promising scaffold to prepare a radiotheranostic system with radioiodine and ²¹¹At.