TY - JOUR

T1 - Dopamine storage capacity in caudate and putamen of patients with early Parkinson's disease: correlation with asymmetry of motor symptoms

AU - Kumakura, Yoshitaka

AU - Gjedde, Albert

AU - Danielsen, Erik H

AU - Christensen, Søren

AU - Cumming, Paul

PY - 2006

Y1 - 2006

N2 - Conventional graphical analysis of positron emission tomography (PET) recordings of the cerebral uptake of the DOPA decarboxylase substrate [(18)F]fluorodopa (FDOPA) assumes irreversible trapping of [(18)F]fluorodopamine formed in the brain. However, 4-h long PET recordings allow the estimation of a rate constant for elimination of [(18)F]fluorodopamine from the brain (k(loss)), from which can be calculated an effective distribution volume (EDV(1)), which is an index of [(18)F]fluorodopamine storage capacity. We earlier developed a method employing 2-h long FDOPA recordings for the estimation of k(loss) and EDV, here defined as EDV(2). This method is based on subtraction of the calculated brain concentrations of the FDOPA metabolite O-methyl-FDOPA, rather than the subtraction of the entire radioactivity in a reference region. We now extend this method for the parametric mapping of these parameters in the brain of healthy aged volunteers and patients with Parkinson's disease (PD), with asymmetry of motor symptoms. For parametric mapping, we use a novel application of a multilinear solution for the two-tissue compartment FDOPA model. We also test a new application of the Logan graphical analysis for mapping of the FDOPA distribution volume at equilibrium. The estimates of k(loss) and EDV(2) were more sensitive for the discrimination of biochemical abnormality in the putamen of patients with early PD relative to healthy aged subjects, than was the conventional net influx estimate. Of the several methods, multilinear estimates of EDV(2) were most sensitive for discrimination of PD and normal putamen. However, k(loss) was most sensitive for detecting biochemical asymmetry in the putamen of PD patients, and only k(loss) also detected in the caudate of PD patients a decline in the retention of [(18)F]fluorodopamine relative to healthy aged control subjects.

AB - Conventional graphical analysis of positron emission tomography (PET) recordings of the cerebral uptake of the DOPA decarboxylase substrate [(18)F]fluorodopa (FDOPA) assumes irreversible trapping of [(18)F]fluorodopamine formed in the brain. However, 4-h long PET recordings allow the estimation of a rate constant for elimination of [(18)F]fluorodopamine from the brain (k(loss)), from which can be calculated an effective distribution volume (EDV(1)), which is an index of [(18)F]fluorodopamine storage capacity. We earlier developed a method employing 2-h long FDOPA recordings for the estimation of k(loss) and EDV, here defined as EDV(2). This method is based on subtraction of the calculated brain concentrations of the FDOPA metabolite O-methyl-FDOPA, rather than the subtraction of the entire radioactivity in a reference region. We now extend this method for the parametric mapping of these parameters in the brain of healthy aged volunteers and patients with Parkinson's disease (PD), with asymmetry of motor symptoms. For parametric mapping, we use a novel application of a multilinear solution for the two-tissue compartment FDOPA model. We also test a new application of the Logan graphical analysis for mapping of the FDOPA distribution volume at equilibrium. The estimates of k(loss) and EDV(2) were more sensitive for the discrimination of biochemical abnormality in the putamen of patients with early PD relative to healthy aged subjects, than was the conventional net influx estimate. Of the several methods, multilinear estimates of EDV(2) were most sensitive for discrimination of PD and normal putamen. However, k(loss) was most sensitive for detecting biochemical asymmetry in the putamen of PD patients, and only k(loss) also detected in the caudate of PD patients a decline in the retention of [(18)F]fluorodopamine relative to healthy aged control subjects.

U2 - 10.1038/sj.jcbfm.9600202

DO - 10.1038/sj.jcbfm.9600202

M3 - Journal article

C2 - 16079784

VL - 26

SP - 358

EP - 370

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 3

ER -