Molecular genetics

Neurosciences

Interface Physique Biologie group

Oncology

OPTIBASE

DNA Sequencing Per-operative Imaging

In Vivo Quantificationfor small animals

POCI I and II TOHR, SIC

Study of the glucose metabolism by the SIC-NMR coupling

in animal models of neurodegenerative diseases

Context of nuclear imaging of small animals

¤ detection principle of SIC

¤ model of Sokoloff : kinetics implicated in glucose metabolism Glucose metabolism : interest of the SIC-NMR coupling

Use of Geant4

tracer

Radioactive isotope

molecule

Having information on physiological or biochemical functions

inject in the organism

Follow the evolution of the molecules

Follow the effect of a treatment

Radiodetectors for in vivo study in small animals :

Context and Stakes

Ex vivo Imaging on Tissue Slices

In vivo Measurements

High resolution tomograph : TOHR

(TomographeHaute Résolution)

Intracerebralradiosensitiveprobe : SIC

(SondeIntraCérébrale

)

1 cm

TOHR

123I-Epidepride

SIC

0

2

4

6

8

10

12

0 5 10 15 20 25 30 35 40 45 50 55 60 65

Time (min.)

nC

i/m

l

Malonate-injected striatum

Intact striatum

nCi x 10000/ml of plasma

FDG injection:42.25 MBq

Malonate + FDG

Study of the striatum

28mm

PM Low noise

SIC : Intracerebral radiosensitive probe

Scintillating plastic Fiber =500m or 250m

Clear Fiber

Optical fiber

Counting electronics

1cm

Evaluation of the detection volume

Radioisotopes used for labeling

structures of interest

11C18F

Optic Guide

cerebellumstriatum

Isotope

18F

11C

Type

+

+

Emax(keV)

634

960

Range(mm)

2,3

3,5

Radius(mm)

0,8

1,0

15mm

Intracellular Accumulation

[18]-FDG

circulatingblood

Cs

[18]-FDG

free(tissue)

Ct

K1

K2

[18]-FDG6-

phosphate

(tissue)K4

K3

hexokinase

Fructose-6-phosphate

Model of Sokoloff : kinetics of the glucose modelisation

sample rate of 1 s perform the dynamic modelling

dCsdt

= - K1 Cs + K2 Ct

Study of the glucose metabolism thanks to the SIC-NMR coupling

GLUCOSE

GLUCOSE

glucose 6-phosphate

pyruvate

Kreb ’sCycle

Acetyl CoA

Kreb’s cycle turn-over NMR Spectroscopy [13C]-glucose

hexokinase activity SIC FDG

[13C] glutamate[13C] glutamine

hexokinase

Physiological data in healthy and pathological animal models

First : studies on control animals injection of [18]-FDG and [13C]-glucose

electric stimulation of the leg : study of the somatosensory cortex activation mechanisms of the rat

variation of the cerebral activity level with/without anaesthesia level

To set up the relation between the hexokinase activity level measured by the model of Sokoloff and the Kreb ’s Cycle turn-over

To check experimentally if the hexokinase activity is the limiting step

Subsequently : studies on animal models of neurodegenerative disease

rats treated with 3-Nitropropionic acid (inhibitor of the Kreb ’s cycle)

Differences between control rats and treated rats

Conclusion Use of Geant4 : influence of a magnetic field on the positrons low energy electromagnetic processes relatively easy visualisation of the events utilisation of an intense magnetic field

Objective :

complete the study of the magnetic field influence define the possibilities of Geant4 in a biological or medical context particularly for TOHR and POCI

develop a competence to make simulations for other detectors

3T 7T

B B

0T

18F beta spectrum in water

Group IPB/IPN Orsay

R. Mastrippolito, P. Lanièce, F. Pain, H. Gurden, A. Desbrée, L. Pinot, F. Lefebvre, L. Valentin.

Collaboration « Service Hospitalier Frédéric Joliot » CEA/CNRS Orsay

P. Hantraye, L. Besret, V. Lebon, M.C. Grégoire, G. Bloch.