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

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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

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[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

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15

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25

30

35

0 10 20 30 40 50 60 70

* p < 0.05, * p < 0.005

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[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

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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)

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[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

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I mea

n (

nC

i/ml)

chan

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in R

OI m

ean

(%

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d v

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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?)