Dopamine receptor properties in Parkinson's disease and Huntington's chorea evaluated by positron emission tomography using¹¹C-N-methyl-spiperone

Abstract

Dopaminergic receptor properties in the striatum of patients with Parkinson's disease (PD) and Huntington's chorea (HD) were studied by positron emission tomography (PET), using 11C-N-methyl-spiperone as a dopamine D2 receptor ligand. The time-dependent regional radioactive uptake in the caudate nucleus and the putamen was measured and fitted to a 3-compartment pharmacokinetic model. The rate constant k3 for specific binding to the receptor compartment in the striatum was determined in relation to the binding in regions with a low density of specific binding sites, such as the cerebellum and the frontal cortex . k3, which is a measure of the receptor density, was reduced in one patient with HD but less affected in PD in comparison with healthy controls. The pattern of k3 values calculated from the 6 PD patients is discussed in relation to any side-to-side differences in dopamine receptor densities in hemiparkinsonism and to possible "hypersensitivity" of dopamine receptors in the early stage of the disease and down-regulation in more advanced disease.

Functional imaging in Huntington's disease

“…Feigin and his colleagues Feigin et al, 2001 and Feigin et al, 2007 reported change scores up to 10% using a network approach that suggested different clinical and imaging measures may be needed for different phases of HD. Several studies examined PET correlates of cognitive, choreic and akinetic-rigid phenotypes of HD (Backman et al, 1997, Ginovart et al, 1997, Hagglund et al, 1987, Lawrence et al, 1998, Leenders et al, 1986, Sedvall et al, 1994 and Turjanski et al, 1997). Backman and Farde (Backman et al, 1997) conducted an overview of dopamine and cognitive functioning using PET findings in HD as an impetus.…”

Positron Emission Tomography: Applications In Drug Discovery and Drug Development

“…Common PET Ligands Used to Study Dopamine ReceptorMonitor changes in dopamine production and D2R in response to alcohol or drug abuse[85,86] Study drug PD for schizophrenic patients[100] Study effects of Huntington's and Parkinson's disease on dopamine receptor[101] [ 11 C]-Deprenyl Potent MAO B inhibitor Map MAO A and B in brain[102] …”

Neurodegenerative movement disorders: the contribution of functional imaging

“…Chronic treatment with dopaminergic agents normalizes D2 receptor binding as has been shown with studies using 11 C-methylspiperone and 11 Craclopride PET [33,34].…”