Comparing IV amphetamine-induced 11C raclopride displacement between HRRT and GE advance PET: Implications for high resolution/sensitivity on dopmaine release measures

Background and aims: Psychostimulant-induced displacement of [11C]Raclopride (RAC), often interpreted as a measure of intrasynaptic dopamine release, is increasingly used as a novel tool for examining brain physiology and pathophysiology. Brain dedicated high-performance PET scanners such as the HRRT (High Resolution Research Tomograph, Siemens CPS/CTI) promise to enhance measurements carried out on non-PET CTs/PET-only like the Siemens HR+ and the GE Advance (GEA). Here we test the hypothesis that the 2?3 fold increase in spatial resolution and sensitivity of the HRRT over the GEA offers an improvement in the quantification of binding potentials (BPs) and dopamine release (DAR) measures following psychostimulant challenge. Such documentation may justify the technical challenges of increased slice number (207 vs 35 for the GEA) and reconstruction time (>15 hours for a 90-min, 30-frame acquisition). Methods: Healthy volunteers (age range 22 ? 25, 4 males, 2 females) underwent two 90-minute PET scans each with IV RAC on the HRRT: 1) Scan 1 following an IV bolus of saline, 2) Scan 2 (2.25 hrs later) following 0.3mg/kg IV amphetamine 5 minutes before tracer injection. Studies were reconstructed using the highest resolution (span 3), current Siemens/CPS/CTI reconstruction software, and a 32-node IBM cluster. Images were acquired in list mode and reconstructed to 30 frames. Time-activity curves were generated in the following regions of interest: anterior/posterior caudate and putamen, and ventral striatum. BPs were obtained using the modified simplified reference tissue method (Ichise, et al, 2002). DAR was calculated as the percent change of baseline to post-amphetamine BPs. All measures obtained on the HRRT were compared to 6 matched (for age, sex and race) subjects who completed amphetamine challenges on the GEA. Results: In each matched pair, we calculated percent increase in BP for HRRT vs. GEA. There was a significant increase in both baseline (range 9-27%, mean 16.0 + 6.7% SD) and post-amphetamine BPs (range 6-35%, mean 18.3 + 10.8% SD) across all regions; however, these BP increases between HRRT and GEA were not significantly different between saline and amphetamine scans. Specifically, BPs for the HRRT were higher than GEA BPs in anterior and posterior putamen and anterior caudate (p<0.05), while the increase was not statistically significant for posterior caudate and ventral striatum (p>0.1). There was also no significant change in DAR between the two scanners (p>0.1). Conclusion: These preliminary data sets suggest that the HRRT can successfully measure the relatively robust effect of RAC displacement by IV amphetamine challenge. BPs, as expected by partial volume (PV) effects, were significantly higher with HRRT vs. the GEA. Although the contrast is lower in the post-amphetamine scans, the change in BP between the two scanners was not significantly different between the two scans. Future studies will not only expand the sample size but also apply these comparisons where contrast is even greater between baseline and post-challenge studies, i.e high and low specific activity RAC. Also, formal PV corrections are being developed for the HRRT as they have for the GEA to allow direct comparison between the GEA and the HRRT.