In vivo and ex vivo biodistribution data of [18F]CHDI-650 in mice

Huntington’s disease (HD) is a rare neurodegenerative disorder caused by an expansion of the CAG trinucleotide repeat in exon 1 of the huntingtin (HTT) gene located on the short arm of chromosome 4. This expansion leads to an elongation of the polyglutamine tract encoding the mutant huntingtin (mHTT) protein. Based on the toxic gain-of-function hypothesis, mHTT-lowering interventions are currently among the most promising therapeutic approaches. As part of the effort to identify a 2nd generation mHTT PET ligand, a novel fluorinated radioligand, namely [18F]CHDI-650, was recently developed. [18F]CHDI-650 displayed suitable reversible kinetics in wild-type (WT) mice and non-human primates as well as specific binding to mHTT aggregates in post-mortem human HD brain. In order to ensure the suitability of [18F]CHDI-650 in humans, a dosimetry study is generally recommended in a preclinical species to estimate the radiation exposure due to the radioligand.