Age-related changes in binding of the D2/3 receptor radioligand [11C](+)PHNO in healthy volunteers

Objective Previous imaging studies with positron emission tomography (PET) have reliably demonstrated an age-associated decline in the dopamine system. Most of these studies have focused on the densities of dopamine receptor subtypes D 2/3 R (D 2 R family) in the striatum using antagonist radiotracers that are largely nonselective for D 2 R vs. D 3 R subtypes. Therefore, less is known about any possible age effects in D 3 -rich extrastriatal areas such as the substantia nigra/ventral tegmental area (SN/VTA) and hypothalamus. This study sought to investigate whether the receptor availability measured with [ 11 C](+)PHNO, a D 3 R-preferring agonist radiotracer, also declines with age. Methods Forty-two healthy control subjects (9 females, 33 males; age range 19–55 years) were scanned with [ 11 C](+)PHNO using a High Resolution Research Tomograph (HRRT). Parametric images were computed using the simplified reference tissue model (SRTM2) with cerebellum as the reference region. Binding potentials ( BP ND ) were calculated for the amygdala, caudate, hypothalamus, pallidum, putamen, SN/VTA, thalamus, and ventral striatum and then confirmed at the voxel level with whole-brain parametric images. Results Regional [ 11 C](+)PHNO BP ND displayed a negative correlation between receptor availability and age in the caudate ( r = − 0.56, corrected p = 0.0008) and putamen ( r = − 0.45, corrected p = 0.02) in healthy subjects (respectively 8% and 5% lower per decade). No significant correlations with age were found between age and other regions (including the hypothalamus and SN/VTA). Secondary whole-brain voxel-wise analysis confirmed these ROI findings of negative associations and further identified a positive correlation in midbrain (SN/VTA) regions. Conclusion In accordance with previous studies, the striatum (an area rich in D 2 R) is associated with age-related declines of the dopamine system. We did not initially find evidence of changes with age in the SN/VTA and hypothalamus, areas previously found to have a predominantly D 3 R signal as measured with [ 11 C](+)PHNO. A secondary analysis did find a significant positive correlation in midbrain (SN/VTA) regions, indicating that there may be differential effects of aging, whereby D 2 R receptor availability decreases with age while D 3 R availability stays unchanged or is increased.