[18F]Fallypride PET measurement of striatal and extrastriatal dopamine D 2/3 receptor availability in recently abstinent alcoholics.
Positron emission tomography (PET) shows reduced binding of the dopamine D(2/3)  antagonist [(11) C]raclopride in striatum of withdrawn psychostimulant abusers, but not consistently in patients with alcohol dependence (AD). We make first use of the high affinity ligand [(18) F]fallypride to obtain serial measures of D(2/3)  receptor availability in striatal and extrastriatal regions of AD patients undergoing detoxification. Seventeen patients (mean age 44 ± 5y) with AD and 14 age-matched healthy volunteers participated. Each patient underwent [(18) F]fallypride PET upon hospital admission, and again 1-2 weeks later; two patients achieving abstinence, and two with substantial harm reduction had additional PET follow-up at 1 year. Dynamic 180-minute PET recordings were used for volume of interest (VOI)-based and voxel-wise analysis of [(18) F]fallypride binding potential (BP(ND) ). Mean baseline BP(ND)  in striatum of the AD patients (15.7 ± 3.6) was unaltered during short-term follow-up, and did not differ from that in healthy controls (16.8 ± 3.0); however, BP(ND)  was 10-20% lower in thalamus, hippocampus, and insular and temporal cortex of the AD patients (P < 0.05). Age-dependent declines in BP(ND)  were very small in controls, but more pronounced and widespread in the AD group. Striatal and thalamic BP(ND)  increased by 30% in four patients with long-term abstinence or reduced alcohol consumption. VOI-based [(18) F]fallypride PET analyses revealed group differences in D(2/3)  receptor availability primarily in extra-striatal regions. Age-related loss of dopamine D(2/3)  receptors was more pronounced in AD patients. Receptor availability was unaltered by acute withdrawal, but increased in the subgroup of patients with long-term follow-up, suggesting reversibility of receptor changes.
Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Germany. axel.rominger@med.uni-muenchen.de
Axel
A
Rominger
Paul
P
Cumming
Guoming
G
Xiong
Gabriele
G
Koller
Guido
G
Böning
Melanie
M
Wulff
Andreas
A
Zwergal
Stefan
S
Förster
Anthonin
A
Reilhac
Ole
O
Munk
Michael
M
Soyka
Björn
B
Wängler
Peter
P
Bartenstein
Christian
C
la Fougère
Oliver
O
Pogarell
D000328:Adult; D000437:Alcoholism / Q000000981:diagnostic imaging* / Q000378:metabolism; D000704:Analysis of Variance; D001549:Benzamides; D016022:Case-Control Studies; D016000:Cluster Analysis; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D019047:Phantoms, Imaging; D049268:Positron-Emission Tomography / Q000379:methods; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D013695:Temperance; D055815:Young Adult
D001549:Benzamides; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3