No abstract

Objective: Dopamine plays an important role in both the rewarding and conditioning effects of food. These effects involve mesolimbic, mesocortical, and nigrostriatal pathways. In humans, the most consistent finding has been reduced striatal dopamine D 2/3 receptor availability. In striatum, dopamine is inactivated by reuptake via the dopamine transporter (DAT). The aim of the study was to test the hypothesis of lower DAT availability in obese healthy subjects using a selective DAT radiotracer in a sample of subjects with a wide range of BMI values. Design and Methods: Thirty-three healthy subjects with a mean age of 48.4 6 13.3 (range, 21-71) years and a mean BMI of 29.6 6 7.8 kg/m 2 (range, 21.0-49.5) were included in the study. We used [123 I]PE2I and SPECT to measure DAT availability. Results: Using multiple linear regression analyses with striatal DAT as the dependent variable and BMI, age and gender as predictors was performed. We found no correlation between BMI and striatal DAT availability in striatum (P ¼ 0.99), caudate nucleus (P ¼ 0.61), and putamen (P ¼ 0.30). Furthermore, we found no group difference between obese/severely obese (BMI > 30 kg/m 2 ) and normal weight controls (BMI 25 kg/m 2 ). Conclusions: We did not find any correlation between BMI and DAT availability in healthy volunteers.

Current SPECT radioligands available for in vivo imaging of the dopamine transporter (DAT) also show affinity for monoamine transporters other than DAT, especially the serotonin transporter (SERT). The effect of this lack of selectivity for in vivo imaging is unknown. In this study, we compared the SPECT radioligands 123 I-2-b-carbomethoxy-3b-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ( 123 I-FP-CIT) and 123 I-N-(3-iodoprop-2E-enyl)-2-b-carbomethoxy-3b-(4-methylphenyl) ( 123 I-PE2I). 123 I-FP-CIT has a 10-fold higher selectivity than 123 I-FP-CIT for DAT versus SERT. Methods: Sixteen healthy individuals were scanned in random order with both radioligands. The radioligands were administered according to standard recommendations: 123 I-FP-CIT was given as a bolus injection, and the ratio between the striatum and reference tissue was measured after 3 h. 123 I-PE2I was administered in a bolus-infusion setup, and the nondisplaceable binding potential (BP ND ) was measured after 2 h. To assess the contribution of SERT to the overall SPECT signal, SERT was blocked by intravenous citalopram in 6 of the individuals. Results: The striatum-to-reference ratio 2 1 of 123 I-FP-CIT was on average 18% higher than the striatal BP ND of 123 I-PE2I. Equal doses of radioactivity resulted in 3 times higher counting rates for 123 I-FP-CIT than for 123 I-PE2I, both in target and in reference brain regions. Citalopram infusion led to significant reductions in both striatal (22.8% 6 20.4%, P , 0.05) and thalamic (63.0% 6 47.9%, P , 0.05) 123 I-FP-CIT binding ratios, whereas BP ND of 123 I-PE2I was unaltered. Likewise, blocking of SERT led to increased (21% 6 30.1%, P , 0.001) plasma 123 I-FP-CIT, probably as a result of significant blocking of peripheral SERT binding sites. By contrast, plasma 123 I-PE2I remained stable. Conclusion: 123 I-FP-CIT and 123 I-PE2I had approximately the same targetto-background ratios, but per injected megabecquerel, 123 I-FP-CIT gave rise to 3-fold higher cerebral counting rates. We found that 123 I-FP-CIT, but not 123 I-PE2I, brain images have a highly interindividual but significant signal contribution from SERT. Whether the SERT signal contribution is of clinical importance needs to be established in future patient studies.

Clinical 123 I-2-b-carbomethoxy-3b-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ( 123 I-FP-CIT) SPECT studies are commonly performed and reported using visual evaluation of tracer binding, an inherently subjective method. Increased objectivity can potentially be obtained using semiquantitative analysis. In this study, we assessed whether semiquantitative analysis of 123 I-FP-CIT tracer binding created more reproducible clinical reporting. A secondary aim was to determine in what form semiquantitative data should be provided to the reporter. Methods: Fifty-four patients referred for the assessment of nigrostriatal dopaminergic degeneration were scanned using SPECT/CT, followed by semiquantitative analysis calculating striatal binding ratios (SBRs) and caudate-to-putamen ratios (CPRs). Normal reference values were obtained using 131 healthy controls enrolled on a multicenter initiative backed by the European Association of Nuclear Medicine. A purely quantitative evaluation was first performed, with each striatum scored as normal or abnormal according to reference values. Three experienced nuclear medicine physicians then scored each striatum as normal or abnormal, also indicating cases perceived as difficult, using visual evaluation, visual evaluation in combination with SBR data, and visual evaluation in combination with SBR and CPR data. Intra-and interobserver agreement and agreement between observers and the purely quantitative evaluation were assessed using k-statistics. The agreement between scan interpretation and clinical diagnosis was assessed for patients with a postscan clinical diagnosis available (n 5 35). Results: The physicians showed consistent reporting, with a good intraobserver agreement obtained for the visual interpretation (mean k 6 SD, 0.95 6 0.029). Although visual interpretation of tracer binding gave good interobserver agreement (0.80 6 0.045), this was improved as SBRs (0.86 6 0.070) and CPRs (0.95 6 0.040) were provided. The number of striata perceived as difficult to interpret decreased as semiquantitative data were provided (30 for the visual interpretation; 0 as SBR and CPR values were given). The agreement between physicians' interpretations and the purely quantitative evaluation showed that readers used the semiquantitative data to different extents, with a more experienced reader relying less on the semiquantitative data. Good agreement between scan interpretation and clinical diagnosis was seen. Conclusion: A combined approach of visual assessment and semiquantitative analysis of tracer binding created more reproducible clinical reporting of 123 I-FP-CIT SPECT studies. Physicians should have access to both SBR and CPR data to minimize interobserver variability.