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Molecular genetics

Interface Physique Biologie group. Molecular genetics. Oncology. Neurosciences. Per-operative Imaging. In Vivo Quantification for small animals. DNA Sequencing. TOHR, SIC. POCI I and II. OPTIBASE. Study of the glucose metabolism by the SIC-NMR coupling

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Molecular genetics

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  1. Interface Physique Biologie group Molecular genetics Oncology Neurosciences Per-operative Imaging In Vivo Quantification for small animals DNA Sequencing TOHR, SIC POCI I and II OPTIBASE

  2. 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

  3. Radioactive isotope molecule Follow the evolution of the molecules Having information on physiological or biochemical functions inject in the organism tracer Follow the effect of a treatment

  4. Radiodetectors for in vivo study in small animals : Context and Stakes In vivo Measurements High resolution tomograph : TOHR (Tomographe Haute Résolution) Ex vivo Imaging on Tissue Slices Intracerebral radiosensitive probe : SIC (Sonde IntraCérébrale) 1 cm

  5. 12 Malonate-injected striatum Intact striatum 10 nCi x 10000/ml of plasma 8 6 nCi/ml 4 2 0 0 5 10 15 20 25 30 35 40 45 50 55 60 65 Time (min.) FDG injection: 42.25 MBq Study of the striatum SIC TOHR 28mm Malonate + FDG 123I-Epidepride

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

  7. Emax (keV) Range (mm) Radius (mm) Type Isotope 11C + 2,3 18F 634 0,8 + 11C 960 3,5 1,0 18F Evaluation of the detection volume • Radioisotopes used for labeling Optic Guide • structures of interest 15mm cerebellum striatum

  8. hexokinase K3 K1 [18]-FDG circulatingblood Cs [18]-FDG free(tissue) Ct [18]-FDG6-phosphate (tissue) K2 K4 Fructose-6-phosphate dCs = - K1 Cs + K2 Ct dt  sample rate of 1 s  perform the dynamic modelling  Model of Sokoloff : kinetics of the glucose modelisation Intracellular Accumulation

  9. glucose 6-phosphate Study of the glucose metabolism thanks to the SIC-NMR coupling GLUCOSE  hexokinase activity SIC FDG GLUCOSE hexokinase pyruvate Acetyl CoA Kreb’s cycle turn-over NMR Spectroscopy [13C]-glucose Kreb ’s Cycle [13C] glutamate [13C] glutamine

  10. 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

  11. 0T Conclusion  Use of Geant4 : influenceof 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 18F beta spectrum in water

  12. 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.

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