Design and Evaluation of [F]CHDI-650 as a Positron Emission Tomography Ligand to Image Mutant Huntingtin Aggregates.

Therapeutic interventions are being developed for Huntington's disease (HD), a hallmark of which is mutant huntingtin protein (mHTT) aggregates. Following the advancement to human testing of two [C]-PET ligands for aggregated mHTT, attributes for further optimization were identified. We replaced the pyridazinone ring of CHDI-180 with a pyrimidine ring and minimized off-target binding using brain homogenate derived from Alzheimer's disease patients.

Synthesis and Preclinical Evaluation of [C]AZ11895530 for PET Imaging of the Serotonin 1A Receptor.

The serotonin 1A (5-HT) receptor is a G-protein-coupled receptor implicated in the pathophysiology of several neuropsychiatric and neurodegenerative disorders. We here report the preparation of two candidate 5-HT radioligands, [C]AZ11132132 ([C]) and [C]AZ11895530 ([C]), and their subsequent evaluation using autoradiography and using positron emission tomography (PET). Compounds and were radiolabeled at high radiochemical purity (>99%) and high molar activity (>38 GBq/μmol) by heteroatom methylation with [C]methyl iodide.