1. Quantification of [ 11 C]FLB 457 binding in the human brain with PET before and after PVE correction Judit Sóvágó Karolinska Institutet Department of Clinical Neuroscience HBM2004 Satellite meeting

2. The influence of PVE on estimates of radioligand uptake BP 5-HT 2A receptors increased with 4-16% after PVC Interregional differences of 5-HT 2A density detected only after PVC Estimates of influx and metabolism of 18 F-DOPA altered in region specific manner after PVC Signal under- or overestimation due to PVE

3. To estimate the influence of PVE on the measured regional uptake of [ 11 C]FLB 457 Study aims To evaluate the performance of different PVE correction algorithms in PET studies with [ 11 C]FLB 457: Meltzer Müller-Gärtner Rousset

4. Image analysis 1.Image acquisition: 6 subjects, T2w. MR, [ 11 C]FLB 457 PET 2.Segmentation: automated and manual 3.Coregistration: manual, image overlay method (MARS) 4.PVE correction: PVE developed within project QLG3-CT2000-00594 5.ROI definition: automated and manual

5. Quantification of ROI data Standard 3 compartment model CPCP CFCF CBCB K1K1 k3k3 k2k2 k4k4 BP = k 3 /k 4 DV (tot) = (K 1 /k 2 )(1+k 3 /k 4 )

6. [ 11 C]FLB 457 uptake in the brain time (min) ROI mean (nCi/ml) thalamusputamen caudateamygdala parietal c.occipital c. temporal c.frontal c. white matter cerebellum Caud.Put.Thal.Amyg.Temp.Front.Pariet.Occ.Cb. K10.490.560.490.370.410.450.440.480.47 k20.04 0.100.090.110.120.440.480.13 k30.110.090.08 0.050.04 0.01 k40.030.020.040.030.04 0.05

7. [ 11 C]FLB 457 uptake in the brain after PVE correction according to Meltzer time (min) ROI mean (nCi/ml) thalamusputamen caudateamygdala parietal c.occipital c. temporal c.frontal c. white matter cerebellum Caud.Put.Thal.Amyg.Temp.Front.Pariet.Occip. K1+14.2*+1.0*+7.2*+11.1*+17.4*+24.9*+32.3*+18.5* k2-1.2+1.4+3.4+5.3+6.3*+3.9+4.5*+3.1 k3-3.4+0.5+6.4+5.8+13.4+3.5+6.7+7.7 k4+4.7-4.2+3.0*+1.0+9.2+0.4+0.8+5.3 time (min) change in ROI mean (% of uncorrected values) * p < 0.05, * p < 0.005

8. [ 11 C]FLB 457 uptake in the brain after PVE correction according to Müller-Gärtner time (min) Caud.Put.Thal.Amyg.Temp.Front.Pariet.Occip. K1+28.3*+15.3*+15.8*+14.3*+39.1*+50.1*+70.5*+54.7* k2+6.4+2.3+7.8+11.9*+18.3*+13.0*+16.2*+9.3* k3+7.2+19.7+6.2+11.2+14.1+3.2+2.3+15.9* k4-5.7+14.8-2.7 -5.1-6.2-7.6-15.4 time (min) * p < 0.05, * p < 0.005 thalamusputamen caudateamygdala parietal c.occipital c. temporal c.frontal c. white matter cerebellum ROI mean (nCi/ml) change in ROI mean (% of uncorrected values)

9. [ 11 C]FLB 457 uptake in the brain after PVE correction according to Rousset time (min) Caud.Put.Thal.Amyg.Temp.Front.Pariet.Occip. K1--+15.1*-5.4+41.8*+55.3*+73.8*+58.1* k2--+3.9-13.3+19.4*+13.0*+12.4*+10.7* k3--+19.9+75.3*+33.5*+5.8 -1.2 k4--+4.6+2.2+12.5+9.9+10.2+17.2* time (min) * p < 0.05, * p < 0.005 thalamusputamen caudateamygdala parietal c.occipital c. temporal c.frontal c. white matter cerebellum ROI mean (nCi/ml) change in ROI mean (% of uncorrected values)

10. 0.0 5.0 10.0 15.0 20.0 25.0 80.0 100.0 120.0 PutamenCaudateThalamusAmygdalaTemp. c.Front. c.Pariet. c.Occipit. c. Total distribution volume (DV (tot) ) VD(tot) PET Meltzer Müller-Gärtner Rousset * p < 0.05, * p < 0.005 * * * * ** * ** * ** * ** * * *

11. Binding potential (BP) BP * * * * * * ** PET Meltzer Müller-Gärtner Rousset * p < 0.05, * p < 0.005

12. Conclusions [ 11 C]FLB 457 binding is underestimated to the highest degree in the temporal cortex and the amygdala. DV tot is more susceptible to PVE than BP. The applied PVE correction algorithms recovered the regional activity loss with different efficacy: –Meltzer: least efficient –Müller-Gärtner: increased DV tot and BP –Rousset: increased DV tot, enhanced differences in BP (Comparison with receptor density obtained with in vitro methods?)