translational study of the modulation of fosfodiesterase type 10A expression by dopaminergic neurotransmission using molecular imaging

Phosphodiesterases are enzymes that break down important signaling molecules (cGMP and cAMP). The phosphodiesterase subtype 10A (PDE10A) is present only in a specific substructure in the brain (“striatum”) which is related to movement disorders such as Huntington’s (HD) and Parkinson’s disease (PD). PDE10A is also a new drug target for treatment of schizophrenia.  We have developed a radioactive substance (“radiotracer”) that binds to PDE10A. After injection of the tracer we can visualize and quantify the level of PDE10A present in brain of laboratory animals and also in man, using a dedicated scanner (positron emission camera, “PET” camera).

Within this project we want to explore how the level of PDE10A in brain is affected in animal models of movement disorders (PD and HD).  We will study how PDE10A is affected by medication frequently prescribed to patients with these illnesses and substances such as amphetamine and cocaine that strongly interfere with neurochemical signaling in the striatum. We will verify the safety of the tracer for human application by quantifying the radiation dose that is absorbed after injection of the radiotracer in man.  Different approaches for an optimal scan procedure and mathematical processing of the PET scan data will be compared. The variability of the quantification of the level of PDE10A of this PET scan method will be determined by repeated injection in human volunteers.