The relationship between subcortical brain volume and striatal dopamine D2/3 receptor availability in healthy humans assessed with [11 C]-raclopride and [11 C]-(+)-PHNO PET

Hum Brain Mapp. 2017 Nov;38(11):5519-5534. doi: 10.1002/hbm.23744. Epub 2017 Jul 28.


Background: Abnormalities in dopamine (DA) and brain morphology are observed in several neuropsychiatric disorders. However, it is not fully understood how these abnormalities may relate to one another. For such in vivo findings to be used as biomarkers for neuropsychiatric disease, it must be understood how variability in DA relates to brain structure under healthy conditions. We explored how the availability of striatal DA D2/3 receptors (D2/3 R) is related to the volume of subcortical brain structures in a sample of healthy humans. Differences in D2/3 R availability measured with an antagonist radiotracer ([11 C]-raclopride) versus an agonist radiotracer ([11 C]-(+)-PHNO) were examined.

Methods: Data from 62 subjects scanned with [11 C]-raclopride (mean age = 38.98 ± 14.45; 23 female) and 68 subjects scanned with [11 C]-(+)-PHNO (mean age = 38.54 ± 14.59; 25 female) were used. Subcortical volumes were extracted from T1-weighted images using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm. Partial correlations were used controlling for age, gender, and total brain volume.

Results: For [11 C]-(+)-PHNO, ventral caudate volumes were positively correlated with BPND in the dorsal caudate and globus pallidus (GP). Ventral striatum (VS) volumes were positively correlated with BPND in the VS. With [11 C]-raclopride, BPND in the VS was negatively correlated with subiculum volume of the hippocampus. Moreover, BPND in the GP was negatively correlated with the volume of the lateral posterior nucleus of the thalamus.

Conclusion: Findings are purely exploratory and presented corrected and uncorrected for multiple comparisons. We hope they will help inform the interpretation of future PET studies where concurrent changes in D2/3 R and brain morphology are observed. Hum Brain Mapp 38:5519-5534, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: D2/3 receptors; PHNO; dopamine; morphology; positron emission tomography; raclopride; striatum; volume.

MeSH terms

  • Adult
  • Corpus Striatum / anatomy & histology
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism*
  • Female
  • Hippocampus / anatomy & histology
  • Hippocampus / diagnostic imaging*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Organ Size
  • Oxazines
  • Positron-Emission Tomography
  • Raclopride
  • Radiopharmaceuticals
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / metabolism*
  • Thalamus / anatomy & histology
  • Thalamus / diagnostic imaging*


  • DRD2 protein, human
  • DRD3 protein, human
  • Oxazines
  • Radiopharmaceuticals
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • naxagolide
  • Raclopride