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Institut Pluridisciplinaire Hubert-Curien UMR 7178, UDS, CNRS-IN 2 P 3

Nautilus Pompilius. Biomedical Applications @ IN 2 P 3. David Brasse. Institut Pluridisciplinaire Hubert-Curien UMR 7178, UDS, CNRS-IN 2 P 3. Therapy. Diagnosis. Radio-Immunotherapy Hadrontherapy Surgery. Clinical Exam Medical & Molecular Imaging Contrast Agent. GDR MI2B

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Institut Pluridisciplinaire Hubert-Curien UMR 7178, UDS, CNRS-IN 2 P 3

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  1. Nautilus Pompilius Biomedical Applications @ IN2P3 David Brasse Institut Pluridisciplinaire Hubert-Curien UMR 7178, UDS, CNRS-IN2P3

  2. Therapy Diagnosis Radio-Immunotherapy Hadrontherapy Surgery Clinical Exam Medical & Molecular Imaging Contrast Agent GDR MI2B Instruments and Methods against Cancer Bioinformatics Fundamental Research Radiobiology: particle interaction / cell In vitro Imaging Cellular Imaging In vivo Imaging Modeling & Simulation (Geant4, Gate) Reconstruction Algorithms

  3. Diagnosis Improve Spatial Resolution & Detection Efficiency of Positron Emission Tomography (PET) - Time Of Fly (TOF) - Dedicated Readout Electronics - Crystal/photodetectors coupling - Innovative Instrumentation (Sc-44 PET 3γ) - Reconstruction Algorithms Molecular Imaging should be Accurate, at an early stage, predictive. LAPPD Project (Fermilab, UC) 3D OSEM + TOF FORE + 2D OSEM LPC Clermont, IMNC, CPPM, IPHC

  4. Diagnosis Molecular Imaging should be Accurate, at an early stage, predictive. Development of new radiolabeled molecules for PET - Two Research and Production Sites (ARRONAX, IPHC) - Innovative Radionuclide for Nuclear Medicine - Rb-82, Ge-68/Ga-68, Cu-64/67, Sc-44/47, Zr-89 - Research in Radiochemistry Tumor angiogenesis (FDG/Cu-DOTA) Tc-99m / Rb-82 Subatech, IPHC

  5. Small Animal Imaging Platform: Sequential Approach µSPECT µCT Screening 2D (fused images) IPHC

  6. CT PET+CT Small Animal Imaging Platform: Combined Approach = + ClearPET (EPFL) XPAD (CPPM) XPAD3 camera RX Tube Conventional CT / Spectral CT PET modules CPPM

  7. Objectives: • Avoid the bias introduced by the anesthesia • Real time behavioral study • Multimodal Imaging approach First Prototype Implant test Small Animal Imaging: Awake…PixSic Project IMNC, CPPM

  8. Simulation Tools: GATE Courtesy of C Morel, CPPM To design: - Prototypes To optimize: - Acquisition protocols - Reconstruction algorithms To improve: - Quantification - Corrections Collaboration openGATE CEA/SHFJ

  9. Simulation is also used for Radiobiology: Geant4-DNA « A major challenge lies in providing a sound mechanistic understanding of low-dose radiation carcinogenesis » L. Mullenders et al. (2009), Nature Reviews Cancer Objective : to adapt the general purpose Geant4 Monte Carlo toolkit for the simulation of interactions of radiation with biological systems at the cellular and DNA level (« microdosimetry ») Example: single cell irradiation by 3 MeV alpha particles in a high resolution cellular Phantom. Collaboration Geant4-DNA

  10. Validation by Experimental Facilities CENBG, LPC Clermont

  11. Hadrontherapy Photon Carbon Objective: Optimize the Treatment Planning System (TPS) for Carbon Dose Measurement TPS Dose Calculation Dose Control Detector Simulations Beam Control Physical Data & Model Biological Data & Model Imaging System ETOILE, ARCHADE, ENVISION (FP7) LPC Caen, LPC Clermont, IPNL, IMNC, IPHC, CPPM

  12. (1) (2) (3) Individual cell Cluster of cells Isotope for Therapy Principle of Radio-Immunotherapy: - (1) Specific recognition of cancer cells (eg monoclonal Ab’s, Ab-fragments, peptides) + (2) Chelate/Linker (derivatives of DTPA, DOTA) + (3) Effective killing β-: Cu-67, Sc-47 α: At-211 Applications for Alpha-Immunotherapy: - Monocellular cancers (eg Leukemia) - Micrometastatic disease - Minimal residual disease after chemotherapy - Residual tumor tissue after tumor resection ARRONAX, Subatech

  13. Per-Operative Systems Brain Tumors Sentinel Lymph Node Biopsy Mainly dedicated to glioma radioguided surgery. Objective: Localization and excision of brain tumors during surgery 1- To check the radioactivity distribution before the surgery (γ camera) 2- To localize the SLNs during the surgery (γ probe + γ camera) 3- To check the removal of all SLN after the surgery (γ camera) Optical and β Detection + Excision Tool IPHC, IMNC

  14. Conclusions LPC Clermont LPC Caen LAL Orsay IPNL Lyon IMNC Orsay CENBG Bordeaux IPHC Strasbourg CPPM Marseille Subatech Nantes LPSC Grenoble CSNSM Orsay • An increasing number of IN2P3 laboratories are involved in Biomedical Applications • Mainly devoted against cancer • From fundamental researches to therapeutic approaches • Involved in European and International collaborations • PI Geant4-DNA • PI openGate • … Thank you for your attention

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