Design of Radioiodinated Pharmaceuticals: Structural Features Affecting Metabolic Stability towards in Vivo Deiodination

European Journal of Organic Chemistry
Lorenzo CavinaFloris P J T Rutjes

Abstract

Radioiodinated pharmaceuticals are convenient tracers for clinical and research investigations because of the relatively long half-lives of radioactive iodine isotopes (i.e., (123)I, (124)I, and (131)I) and the ease of their chemical insertion. Their application in radionuclide imaging and therapy may, however, be hampered by poor in vivo stability of the C-I bond. After an overview of the use of iodine in biology and nuclear medicine, we present here a survey of the catabolic pathways for iodinated xenobiotics, including their biodistribution, accumulation, and biostability. We summarize successful rational improvements in the biostability and conclude with general guidelines for the design of stable radioiodinated pharmaceuticals. It appears to be necessary to consider the whole molecule, rather than the radioiodinated fragment alone. Iodine radionuclides are generally retained in vivo on sp(2) carbon atoms in iodoarenes and iodovinyl moieties, but not in iodinated heterocycles or on sp(3) carbon atoms. Iodoarene substituents also have an influence, with increased in vivo deiodination in the cases of iodophenols and iodoanilines, whereas methoxylation and difluorination improve biostability.

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Citations

Feb 12, 2019·Chembiochem : a European Journal of Chemical Biology·Veronika RoseckerHannes Mikula
Dec 7, 2019·Chemistry : a European Journal·Jacob C LutterVincent L Pecoraro
Jun 2, 2020·Chemical & Pharmaceutical Bulletin·Miho AokiKazuma Ogawa
Nov 16, 2019·Scientific Reports·Takuya YokoyamaMasatoshi Fujita
Oct 23, 2020·Journal of Labelled Compounds & Radiopharmaceuticals·Trevor FerrisEric O Aboagye
Mar 30, 2021·Bioconjugate Chemistry·Yijing ZhangJuan Diwu
May 6, 2020·The Journal of Organic Chemistry·Emmanuelle DubostThomas Cailly
Feb 6, 2018·Molecular Pharmaceutics·Martina BenešováCristina Müller
May 21, 2020·Molecular Pharmaceutics·Louis Allott, Eric O Aboagye
Feb 7, 2020·Journal of Medicinal Chemistry·Toshimitsu OkamuraMing-Rong Zhang
Oct 29, 2021·Journal of Medicinal Chemistry·Hiroyuki SuzukiYasushi Arano

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Methods Mentioned

BETA
acylation

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