Molecular genetics Neurosciences Interface Physique Biologie group Oncology OPTIBASE DNA Sequencing Per-operative Imaging In Vivo Quantification for 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 (Tomographe Haute Résolution) Intracerebral radiosensitive probe : SIC (Sonde IntraCérébrale) 1 cm

TOHR 123 I-Epidepride SIC Malonate + FDG Study of the striatum 28mm

PM Low noise SIC : Intracerebral radiosensitive  probe Scintillating plastic Fiber  =500  m or 250  m Clear Fiber Optical fiber Counting electronics 1cm

Evaluation of the detection volume  Radioisotopes used for labeling  structures of interest 11 C 18 F Optic Guide cerebellum striatum Isotope 18F 11C Type ++ ++ Emax (keV) Range (mm) 2,3 3,5 Radius (mm) 0,8 1,0 15mm

Intracellular Accumulation [18]-FDG circulating blood Cs [18]-FDG free (tissue) Ct K1 K2 [18]-FDG 6- 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 dCs dt = - K1 Cs + K2 Ct

Study of the glucose metabolism thanks to the SIC-NMR coupling GLUCOSE glucose 6-phosphate pyruvate Kreb ’s Cycle Acetyl CoA  Kreb’s cycle turn-over NMR Spectroscopy [ 13 C]-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 3T7T BB 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.