Positron emission tomography measures of benzodiazepine receptors in Huntington's disease.
We performed positron emission tomographic (PET) measurements of the regional distribution volume of benzodiazepine receptors and regional glucose metabolism in 6 drug-free patients with early Huntington's disease following injection of [11C]flumazenil, a nonsubtype selective central benzodiazepine receptor antagonist, and 18F-2-fluoro-2-deoxy-D-glucose, respectively. Flumazenil data were analyzed with a recently developed two-compartment, two-parameter tracer kinetic model. Benzodiazepine receptor density is related to distribution volume for flumazenil. In comparison with a group of healthy volunteers, benzodiazepine receptor density was significantly decreased in the caudate nucleus. Glucose metabolism was significantly reduced not only in the caudate nucleus but also in the putamen and thalamus. The changes in benzodiazepine receptor density observed in the caudate nucleus are commensurate with data obtained in postmortem autoradiographic studies of receptor density. Based on such postmortem studies we also anticipated changes in putamen and thalamic benzodiazepine receptor density. However, relatively little is known on receptor changes in early Huntington's disease, because the autoradiographic data available were obtained mostly in patients with advanced disease. The decreased glucose metabolism in the caudate and putamen agrees well with previously published results of PET studies, whereas metabolic impairment of the thalamus has not yet been described in Huntington's disease. The present study suggests that regional metabolism and gamma-aminobutyric acid (GABA)-benzodiazepine receptor changes in subcortical structures of patients with early Huntington's disease do not occur with the same time course: Caudate benzodiazepine receptor density is already severely impaired when other subcortical structures reveal only minor abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Holthoff
V A
VA
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor.
Koeppe
R A
RA
Frey
K A
KA
Penney
J B
JB
Markel
D S
DS
Kuhl
D E
DE
Young
A B
AB
D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D005442:Flumazenil / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil