Test-retest variability of high resolution positron emission tomography (PET) imaging of cortical serotonin (5HT2A) receptors in older, healthy adults

The average difference in the binding potential (BPND) as measured on the two occasions in the frontal and temporal cortical regions ranged between 2 and 12%, with the lowest intraclass correlation coefficient in anterior cingulate regions.We conclude that the test-retest variability of [18F]-setoperone PET in elderly subjects is comparable to that of [18F]-setoperone and other 5HT2AR radiotracers in younger subject samples.As the proportion of the aged in the population increases, cognitive impairment and depression in older adults has become a public health priority. Twenty-five to thirty percent of nursing home residents are taking second generation antipsychotic medications [1], for which the serotonin 2A receptor (5HT2AR) is a target of action. In addition, selective serotonin reuptake inhibitors (SSRIs) are first line drugs in the management of depression and have recently been studied for the management of psychological and behavioural manifestations of dementia [2,3]. The efficacy and/or adverse effects of atypical antipsychotics (e.g., risperidone [4]; and SSRIs in these contexts is predicated upon pre- and post-synaptic effects at several central nervous system serotonin receptors, so that the ability to quantify serotonin receptors in vivo in older subjects is critical to understanding more about the mechanisms of action of the available medications and to inform the development of more effective treatments.Autoradiography findings [5-7] and radiotracer PET studies [8-15] have reported both increases and decreases in 5HT2AR in major depression in younger patients, but no change in older depressed patients (in one study), and decreases in Alzheimer's disease (AD). In addition to the reported 5HT2AR reduction due to neuropsychiatric disorders, there are significant declines in 5HT2AR binding in normal aging, that are independent of disease state [8,12]. Given the decrease in 5HT2AR binding with age and disease, it is important to assess the stability of 5HT