Benzodiazepine receptor quantification in Huntington's disease with [123I]iomazenil and SPECT
L H Pinborga, C Videbæka, S G Hasselbalcha, S A Sørensenb, A Wagnerc, O B Paulsona, G M Knudsena
a Neurobiology
Research Unit 9201, Rigshospitalet, 9 Blegdamsvej, Copenhagen, DK-2100,
Denmark, b Institute of Medical Genetics, IMBG Panum
Instituttet, 3 Blegdamsvej, Copenhagen, DK-2200, Denmark, c Department of Radiology,
Rigshospitalet, 9 Blegdamsvej, Copenhagen, DK-2100, Denmark
Correspondence to: Dr L H Pinborg pinborg{at}pet.rh.dk
Received 13 April 2000 and in revised form 26 September 2000;
Accepted 4 October
2000
OBJECTIVES
Increasing
evidence suggests that metabolic changes predate neuronal death in
Huntington's disease and emission tomography methods (PET and SPECT)
have shown changes in glucose consumption and receptor function in
early and possibly even presymptomatic disease. Because the
GABAA-benzodiazepine receptor complex (BZR) is
expressed on virtually all cerebral neurons BZR density images may be
used to detect neuronal death. In this study the regional cerebral
[123I]iomazenil binding to BZR was determined in patients
with Huntington's disease and normal controls by a steady state method
and SPECT.
METHODSSeven
patients mildly to moderately affected by Huntington's disease and
seven age matched controls were studied. Brain CT was performed on all
subjects. In each subject two [123I]iomazenil-SPECT
measurements were acquiredone with and one without infusion of
flumazenil. The affinity constant of flumazenil (Kd) was calculated
from the paired distribution volumes (DV) and the free plasma
flumazenil concentration. The distribution volume of
[123I]iomazenil in the unblocked condition
(DV0) reflects the ratio between BZR density and Kd.
RESULTSFlumazenil Kd
was similar in the Huntington's disease group and the control group
(11.3 v 11.2 mM). For the Huntington's
disease group a 31% reduction in striatal DV0 (p=0.03) was
found. In the cortical regions, DV0 was similar in patients
and in controls. In Huntington's disease, DV0 correlated
significantly with functional capacity (p=0.04) and chorea symptoms
(p=0.02). The clinically least affected patients displayed
DV0s within the range of those of the control group (19-35
ml/ml).
CONCLUSIONSThe
finding of an unchanged Kd of flumazenil in patients indicates that the
BZR is functionally intact in Huntington's disease. That is, the
reduction in DV0 for BZR represents a selective decrease in
the number of striatal BZRs. DV0 significantly correlated
with functional loss and [123I]iomazenil-SPECT could be
an important tool for validation of the effect of future therapeutic
strategies aimed at limiting oxidative stress and free radicals in
Huntington's disease.
Keywords: Huntington's disease; benzodiazepine receptor; SPECT-iomazenil
© 2001 by Journal of Neurology, Neurosurgery, and Psychiatry
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