Synthesis and (pre)clinical evaluation of PET radioligands for in vivo visualization of phosphodiesterase 10, an enzyme involved in neurological and psychiatric disorders.

Several compounds have been evaluated in cooperation with Johnson & Johnson as PET radioligands for the in vivo visualisation of the PDE10A enzyme, which is highly expressed in the striatum and the pharmacological characterisation of which indicates a potential use of PDE10 inhibitors for treating neurological and psychiatric disorders like schizophrenia. The availiability of PET radioligands for the in vivo visualization of PDE10A is important for early clinical validation of new drugs that engage on this enzyme and allows the study of the expression of PDE10A in different neurological pathologies in man. The aim of this study is to develop an alternative radiosynthesis method for the production of selected radioligands for potential clinical use because the current precursors have a very limited chemical stability. A limited number of derivatives will be further validated preclinically (metabolite analysis, in vivo blocking and displacement µPET imaging studies,....) and the binding potential to PDE10 will be quentified in a rat model of Huntington's disease. After obtaining authorization from the local ethical committee and the Federal Agency of Medicines and Health products, a first in man study will be initiated.

Keywords:First in man study, Preclinical validation, Radiosynthesis, PET, Schizoprenia, PDE10A

Disciplines:Medicinal products