Neopentyl glycol as a scaffold to provide radiohalogenated theranostic pairs of high in vivo stability

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 derivatives 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

Evaluation of Neopentyl Derivatives as A Scaffold for Astatination and Radioiodination

Astatine-211 (211At) is one of the most promising radionuclides for targeted α therapy of cancers and radioiodine such as iodine-123 is useful radionuclide for diagnosis. Because astatine and iodine are the same group, halogen, the same scaffolds could be used for astatination and radioiodination to prepare radiotheranostics compounds. However, the in vivo instability of 211At-labeling agents such as 211At-benzoate limits the application of 211At to various compounds. To overcome the problem and expand the application of 211At-labeled compounds to radiotheranostics, we developed neopentyl derivatives as a novel scaffold for astatination and radioiodination. The stability and biodistribution of 211At or 125I-labeled neopentyl derivatives were compared with reference compounds radiolabeled with 125I or 211At via a conventional method using benzamide.SNMMI2020 Annual Meetin