PET studies of dopamine receptor distribution using [18F]fluoroethylspiperone: findings in disorders related to the dopaminergic system

Abstract

PET studies of dopamine D2-receptor binding were performed in thirty patients with various disorders related to the dopaminergic system and in six healthy controls. Uptake of [18F]fluoroethylspiperone in caudate over three hours was analyzed in terms of several indices of receptor binding:caudate-to-cerebellum activity ratio, concentration of ligand as percentage of injected dose, caudate-to-blood radioactivity ratio, slope of tracer uptake curves, binding potential, kinetic constants of a three compartment model. In 14 patients brain glucose metabolism was also measured. Data on medicated patients demonstrate that the average values of most of the above parameters indicate the decreased number of available D2-receptors whereby, besides an age dependent decline, the caudate-to-cerebellum ratio affords the relatively best distinction among diagnostic groups. In individual cases, large variability among subjects permits only the classification of severe pathologies. Morphological damage and neuronal loss in the striatum may also cause abnormal low values both for the indices of receptor binding and for glucose consumption, thus providing a possible pathogenetic link between receptor dysfunction and impaired energy metabolism.

Positron emission tomography with (18F)methylspiperone demonstrates D2 dopamine receptor binding differences of clozapine and haloperidol

“…In the present study both parameters were calculated (Table 2). With MSP, the striatum to cerebellum ratio at three hours after injection reached about the same values as those observed with FESP previously (Wienhard et al, 1990). However, the use of striatum to cerebellum ratios is limited by an age dependent decrease of spiperone binding.…”

“…Under clozapine treatment a dose-dependent decrease of striatum to cerebellum ratio was not found. The ratios of the controls and of the clozapine treated patients were all within normal range (Wienhard et al, 1990). In patients 4 even an increase of daily clozapine dose from 100rag to 450mg did not have any effect on spiperone binding in the striatum.…”

“…In the present study even an increase of daily clozapine dose from 100mg to 450mg in the same patient had no detectable effect on D2 dopamine receptor occupancy. The striatum to cerebellum ratio remained unaltered in the upper range of normal drug-free individuals (Wienhard et al, 1990). This considerable difference between the receptor binding feature of halo-peridol and clozapine agrees with previous animal studies.…”

Effect of Age on D2 Dopamine Receptors in Normal Human Brain Measured by Positron Emission Tomography and 11C-Raclopride

“…In this study, the radiotracer carbon 11-labeled\x=req-\ raclopride and positron emission tomography were applied to determine the effect of age on striatal D2 dopamine receptors in 32 healthy volunteer subjects (age range, 21 to 68 years; median, 31 years). An index of specific 11C\ x=r eq-\ raclopride binding was calculated for putamen, caudate nucleus, and other brain regions in each subject.…”

Effect of tissue heterogeneity on quantification in positron emission tomography

“…If one of the tissue compartments is irreversible (k4=0), Eq. 7 is the model equation for the total radioactivity concentration at time T. Examples of studies using this common configuration are glucose utilization using [18F]FDG [20] and [l-J I C]-D-glucose [21 ], receptor binding using 3-N-[2'-1SF]fluoroeth_ ylspiperone (FESP) [22,23], cerebral monoamine oxidase B activity (MAO-B) using [J~C]deprenyl [24] and amino acid utilization using [1 IC]methionine [25] or 18F-tyrosine [26]. The effects of heterogeneity for two tracers, FDG and MAO-B, with low and high extraction fraction, respectively, were examined.…”