[18F]Fallypride PET measurement of striatal and extrastriatal dopamine D 2/3 receptor availability in recently abstinent alcoholics

Addict Biol. 2012 Mar;17(2):490-503. doi: 10.1111/j.1369-1600.2011.00355.x. Epub 2011 Oct 3.

Abstract

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emission tomography (PET) shows reduced binding of the dopamine D(2/3) antagonist [(11) C]raclopride in striatum of withdrawn psychostimulant abusers, but not consistently in patients with alcohol dependence (AD).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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcoholism / diagnostic imaging*
  • Alcoholism / metabolism
  • Analysis of Variance
  • Benzamides*
  • Case-Control Studies
  • Cluster Analysis
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism*
  • Female
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Male
  • Middle Aged
  • Phantoms, Imaging
  • Positron-Emission Tomography / methods
  • Pyrrolidines*
  • Radiopharmaceuticals*
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / metabolism*
  • Temperance
  • Young Adult

Substances

  • Benzamides
  • N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide
  • Pyrrolidines
  • Radiopharmaceuticals
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3