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

2021; American Chemical Society; Volume: 64; Issue: 21 Linguagem: Inglês

10.1021/acs.jmedchem.1c01147

1520-4804

Hiroyuki Suzuki, Yuta Kaizuka, Maho Tatsuta, Hiroshi Tanaka, Nana Washiya, Yoshifumi Shirakami, Kazuhiro Ooe, Atsushi Toyoshima, Tadashi Watabe, Takahiro Teramoto, Ichiro Sasaki, Shigeki Watanabe, Noriko S. Ishioka, Jun Hatazawa, Tomoya Uehara, Yasushi Arano,

Chemical Reactions and Isotopes

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.