Neopentyl Glycol as a Scaffold to Provide Radiohalogenated Theranostic Pairs of High Stability.

The high stability of 2,2-dihydroxymethyl-3-[F]fluoropropyl-2-nitroimidazole ([F]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 I-labeled compounds remained stable against nucleophilic substitution, only a I-labeled neopentyl glycol was stable against cytochrome P450 (CYP)-mediated metabolism and showed high stability against deiodination. At-labeled neopentyl glycol also remained stable against both nucleophilic substitution and CYP-mediated metabolism. At-labeled neopentyl glycol showed the biodistribution profiles similar to those of its radioiodinated counterpart in contrast to the I/At-labeled benzoate pair. The urine analyses confirmed that At-labeled neopentyl glycol was excreted in the urine as a glucuronide conjugate with the absence of free [At]At. These findings indicate that neopentyl glycol would constitute a promising scaffold to prepare a radiotheranostic system with radioiodine and At.