Sex correction improves the accuracy of clinical dopamine transporter imaging.

BACKGROUND: In clinical diagnostic imaging, dopamine transporter (DAT) SPECT scans are commonly evaluated using automated semiquantitative analysis software. Age correction is routinely implemented, but usually no sex correction of DAT binding is performed. Since there are sex differences in presynaptic dopaminergic function, we investigated the effect of DAT sex correction in a sample of healthy volunteers who underwent brain [123I]-FP-CIT SPECT. METHODS: Forty healthy elderly individuals (21 men and 19 women) underwent brain [123I]-FP-CIT SPECT, and each subject was examined clinically for motor and non-motor parkinsonian symptoms and signs. Regional specific DAT binding ratios (SBR = [ROI-occ]/occ) were calculated using age correction, and the results were compared to those in normal databases with and without sex correction. The level of regional abnormality was set at 2 standard deviations below the mean values of the reference databases. RESULTS: In the analysis without sex correction, compared to the mean ratio of the reference database, ten healthy individuals (8 men and 2 women) had abnormally low DAT binding ratios, and four individuals (3 men and 1 woman) had borderline low DAT binding ratios in at least one striatal region. When sex correction was implemented, the ratio of one individual was abnormal, and the ratio of one individual was borderline (both males). There were no clinically significant differences in motor or non-motor symptoms between healthy volunteers with abnormal and normal binding. CONCLUSIONS: A considerable number of elderly healthy male subjects can be interpreted to be dopaminergically abnormal if no sex correction of DAT binding is performed. Sex differences in striatal dopaminergic function should be taken into account when DAT imaging is used to assist clinical diagnostics in patients with suspected neurological disorders.

Dopamine transporter binding in symptomatic controls and healthy volunteers: Considerations for neuroimaging trials.

OBJECTIVE: To evaluate possible differences between brain dopamine transporter (DAT) binding in a group of symptomatic parkinsonism patients without dopaminergic degeneration and healthy individuals. BACKGROUND: Dopaminergic neuroimaging studies of Parkinson's disease (PD) have often used control groups formed from symptomatic patients with apparently normal striatal dopamine function. We sought to investigate whether symptomatic patients can be used to represent dopaminergically normal healthy controls. METHODS: Forty healthy elderly individuals were scanned with DAT [123I]FP-CIT SPECT and compared to 69 age- and sex-matched symptomatic patients with nondegenerative conditions (including essential tremor, drug-induced parkinsonism and vascular parkinsonism). An automated region-of-interest based analysis of the caudate nucleus and the anterior/posterior putamen was performed. Specific binding ratios (SBR = [ROI-occ]/occ) were compared between the groups. RESULTS: DAT binding in symptomatic patients was 8.6% higher in the posterior putamen than in healthy controls (p = 0.03). Binding correlated negatively with age in both groups but not with motor symptom severity, cognitive function or depression ratings. CONCLUSIONS: Putaminal DAT binding, as measured with [123I]FP-CIT SPECT, was higher in symptomatic controls than in healthy individuals. The reason for the difference is unclear but can include selection bias when DAT binding is used to aid clinical diagnosis and possible self-selection bias in healthy volunteerism. This effect should be taken into consideration when designing and interpreting neuroimaging trials investigating the dopamine system with [123I]FP-CIT SPECT.