Institut Pluridisciplinaire Hubert-CurienUMR 7178, UDS, CNRS-IN2P3

David Brasse

Biomedical Applications @ IN2P3

Nautilus Pompilius

Fundamental Research

Radiobiology: particle interaction / cellIn vitro ImagingCellular ImagingIn vivo Imaging

Bioinformatics

Therapy

Radio-ImmunotherapyHadrontherapy

Surgery

DiagnosisClinical Exam

Medical & Molecular ImagingContrast Agent

GDR MI2BInstruments and Methodsagainst Cancer

Modeling & Simulation (Geant4, Gate)Reconstruction Algorithms

Molecular Imaging should beAccurate, at an early stage,predictive.

Diagnosis Improve Spatial Resolution & Detection Efficiencyof Positron Emission Tomography (PET)

- Time Of Fly (TOF)- Dedicated Readout Electronics- Crystal/photodetectors coupling- Innovative Instrumentation (Sc-44 PET 3γ)- Reconstruction Algorithms

FORE + 2D OSEM 3D OSEM + TOF

LAPPD Project (Fermilab, UC)

020406080

100120140

0 10 20 30 40

Number of photoelectrons

Tim

ing

reso

lutio

n (p

s)

LPC Clermont, IMNC, CPPM, IPHC

Molecular Imaging should beAccurate, at an early stage,predictive.

Diagnosis

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

Tc-99m / Rb-82Tumor angiogenesis (FDG/Cu-DOTA)

Subatech, IPHC

Small Animal Imaging Platform: Sequential Approach

µCT µSPECT

Screening 2D (fused images)IPHC

Small Animal Imaging Platform: Combined Approach

+

XPAD (CPPM)ClearPET (EPFL)

=

RX TubeXPAD3camera

PET modules

CT PET+CT

Conventional CT / Spectral CT

CPPM

Small Animal Imaging: Awake…PixSic Project

Objectives:

Avoid the bias introduced by the anesthesia

Real time behavioral study

Multimodal Imaging approach

First Prototype

Implant test

IMNC, CPPM

Simulation Tools: GATE

To design:- Prototypes

To optimize:- Acquisition protocols- Reconstruction algorithms

To improve:- Quantification- Corrections

Courtesy of C Morel, CPPM

CEA/SHFJ Collaboration openGATE

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 cellularPhantom.

Collaboration Geant4-DNA

Validation by Experimental Facilities

CENBG, LPC Clermont

Hadrontherapy

Objective: Optimize the Treatment Planning System (TPS) for Carbon

Detector

Dose Measurement

Dose Control

Beam Control

Imaging System

Dose Calculation

Simulations

TPS

Physical Data& Model

Biological Data& Model

Photon Carbon

ETOILE, ARCHADE, ENVISION (FP7)LPC Caen, LPC Clermont, IPNL, IMNC, IPHC, CPPM

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

(1) (2) (3)

Cluster of cells

Individual cell

ARRONAX, Subatech

Per-Operative Systems

Sentinel Lymph Node Biopsy

Optical and β Detection+

Excision Tool

1- To check the radioactivity distributionbefore 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)

Mainly dedicated to glioma radioguided surgery.Objective: Localization and excision of brain tumors during surgery

Brain Tumors

IPHC, IMNC

Conclusions

Thank you for your attention

LPC ClermontLPC CaenLAL OrsayIPNL LyonIMNC OrsayCENBG BordeauxIPHC StrasbourgCPPM MarseilleSubatech NantesLPSC GrenobleCSNSM 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- …