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Quantification of [11C]FLB 457 binding
in the human brain with PET
before and after PVE correction
Judit SóvágóKarolinska Institutet
Department of Clinical Neuroscience
HBM2004 Satellite meeting
The influence of PVE on estimatesof radioligand uptake
• BP 5-HT2A receptors increased with 4-16% after PVC
• Interregional differences of 5-HT2A density detected only after PVC
• Estimates of influx and metabolism of 18F-DOPA altered in region specific manner after PVC
Signal under- or overestimation due to PVE
To estimate the influence of PVE on the measured regional uptake of [11C]FLB 457
Study aims
To evaluate the performance of different PVE correction algorithms in PET studies with [11C]FLB 457:• Meltzer• Müller-Gärtner• Rousset
Image analysis
1. Image acquisition:6 subjects, T2w. MR, [11C]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
Quantification of ROI data
Standard 3 compartment model
CPCF CB
K1 k3
k2 k4
BP = k3/k4
DV(tot) = (K1/k2)(1+k3/k4)
[11C]FLB 457 uptake in the brain
0
200
400
600
800
1000
1200
1400
1600
0 10 20 30 40 50 60 70
time (min)
RO
I mea
n (
nC
i/ml)
thalamus putamencaudate amygdalaparietal c. occipital c.temporal c. frontal c.white matter cerebellum
Caud. Put. Thal. Amyg. Temp. Front. Pariet. Occ. Cb.
K1 0.49 0.56 0.49 0.37 0.41 0.45 0.44 0.48 0.47
k2 0.04 0.04 0.10 0.09 0.11 0.12 0.44 0.48 0.13
k3 0.11 0.09 0.08 0.08 0.05 0.04 0.04 0.04 0.01
k4 0.03 0.02 0.04 0.03 0.04 0.04 0.04 0.05 0.05
0
200
400
600
800
1000
1200
1400
1600
0 10 20 30 40 50 60 70
[11C]FLB 457 uptake in the brain after PVE correction according to Meltzer
time (min)
RO
I mea
n (
nC
i/ml)
thalamus putamencaudate amygdalaparietal 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)
chan
ge
in R
OI m
ean
(%
of
un
corr
ecte
d v
alu
es)
0
5
10
15
20
25
30
35
0 10 20 30 40 50 60 70
* p < 0.05, * p < 0.005
0
200
400
600
800
1000
1200
1400
1600
0 10 20 30 40 50 60 70
[11C]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 -2.7 -5.1 -6.2 -7.6 -15.4
time (min)
* p < 0.05, * p < 0.005
0
10
20
30
40
50
60
70
80
0 10 20 30 40 50 60 70
thalamus putamencaudate amygdalaparietal c. occipital c.temporal c. frontal c.white matter cerebellum
RO
I mea
n (
nC
i/ml)
chan
ge
in R
OI m
ean
(%
of
un
corr
ecte
d v
alu
es)
0
200
400
600
800
1000
1200
1400
1600
0 10 20 30 40 50 60 70
[11C]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 +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
thalamus putamencaudate amygdalaparietal c. occipital c.temporal c. frontal c.white matter cerebellum
-10
0
10
20
30
40
50
60
70
80
0 10 20 30 40 50 60 70
RO
I mea
n (
nC
i/ml)
chan
ge
in R
OI m
ean
(%
of
un
corr
ecte
d v
alu
es)
0.0
5.0
10.0
15.0
20.0
25.0
80.0
100.0
120.0
Putamen Caudate Thalamus Amygdala Temp. c. Front. c. Pariet. c. Occipit. c.
Total distribution volume (DV(tot))V
D(t
ot)
PET
Meltzer
Müller-Gärtner
Rousset
* p < 0.05, * p < 0.005
*
** *
* *
*
* ** * *
** *
* * *
Binding potential (BP)B
P
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
Putamen Caudate Thalamus Amygdala Temp. c. Front. c. Pariet. c. Occipit. c.
**
* * ** **
PET
Meltzer
Müller-Gärtner
Rousset
* p < 0.05, * p < 0.005
Conclusions
• [11C]FLB 457 binding is underestimated to the highest degree in the temporal cortex and the amygdala.
• DVtot 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 DVtot and BP– Rousset: increased DVtot, enhanced differences in
BP(Comparison with receptor density obtained with in vitro methods?)