METABOLOMICS RESEARCHCARMeN project

X

METABOLOMICS Fundamental, clinical & pre-clinical research

Genes

Cancer cells

Cancer tissue

DNA

RNA

Proteins

Metabolites

Dysfunction

Metabolomics research

Metabolomics for cancer research

CARMeN project2.7 millions €

METABOLOMICS Fundamental, clinical & pre-clinical research

University Hospitals of Strasbourg (I.J. Namer, J.P. Bellocq)University of Strasbourg / CNRS (K. Elbayed)Bruker France (M. Piotto)Regional Cancer Institute

Strasbourg’s Hautepierre Hospital11.7 T HRMAS-NMR System

January, 2008

54.7oB0

biological tissue(1-20 mg)

ppm6 4 2 0

HRMAS

withoutHRMAS

METABOLOMICS Fundamental, clinical & pre-clinical research

< 5 min

tumor surgery

dissectionof the tumor sample

tumor data bank

HRMAS-NMR

pathology

molecular biology

Clinical research

METABOLOMICS Fundamental, clinical & pre-clinical research

molecular biology

xenogreffs

HRMAS-NMRpathology

tumor surgery

Pre-clinical research

new traitement

( )Histopathology, molecular biology,

prognosis, medical imaging...Metabolomics data

NMR Metabolomics database in cancerology

( )Statistical models(PCA, PLS-DA)

METABOLOMICS Fundamental, clinical & pre-clinical research

HRMAS-NMR spectroscopy

13C

1H

2D

lactate

acetatebeta-glucosepyruvate

resolution : 10 microM

1D

Pretreatment of 1D spectra

normalization

sampling

Statistical treatmentPCA, PLS-DA

ref.

METABOLOMICS Fundamental, clinical & pre-clinical research

METABOLOMICS Fundamental, clinical & pre-clinical research

Publications:

G Erb, K Elbayed, M Piotto, J Raya, A Neuville, M Mohr, D Maitrot, P Kehrli, IJ Namer : Towards improved grading of malignancy in oligodendrogliomas using metabolomics. Magnetic Resonance in Medicine 59: 959-965, 2008.

M Piotto, FM Moussallieh, B Dillmann, A Imperiale, A Neuville, C Brigand, JP Bellocq, K Elbayed, IJ Namer : Metabolomic characterization of primary human colorectal cancers using high resolution magic angle spinning 1H magnetic resonance spectroscopy. Metabolomics 5: 292-301, 2009.

A Imperiale, K Elbayed, FM Moussallieh, A Neuville, M Piotto, JP Bellocq, P Lutz, IJ Namer : Metabolomic pattern of childhood neuroblastome obtained by 1H high resolution magic angle spinning (HRMAS) NMR spectroscopy. Pediatric Blood & Cancer (in press), 2010.

J Detour, K Elbayed, M Piotto, FM Moussallieh, A Nehlig, IJ Namer : Ultra fast in vivo microwave irradiation for inhanced metabolic stability of brain biopsy samples during HRMAS NMR analysis. Journal of Neurochemistry (submitted), 2010.

N Daci-Youcef, S Froeliech, FM Moussallieh, S Heikkinen, D Dembele, B Lhermitte, K Elbayed, C Koehl, IJ Namer, J Auwerx : Gene expression mapping of HDACs and co-factors correlates with metabolomic profile and helps to idendify human brain tumor subgroup signatures. In preparation for Cancer Research, 2010.

D Ben Sellem, K Elbayed, A Neuville, FM Moussallieh, M Piotto, JP Bellocq, IJ Namer : Metabolomic approach to ovarians cancers: HRMAS NMR investigation. In preparation for Gynecologic Oncology, 2010.

K Elbayed, FM Moussallieh, A Neuville, H Lang, M Piotto, JP Bellocq, IJ Namer : Metabolomic approach to renal cancers: HRMAS NMR investigation. In preparation for NMR in Biomedicine, 2010.

METABOLOMICS Fundamental, clinical & pre-clinical research

com

pone

nt 2

Metabolomic identification of biomarkers

METABOLOMICS Fundamental, clinical & pre-clinical research

Cancer vs. normal tissue

component 1

single i.v. injection of 20 mM [13C 2]-XXX

tumor resection HRMAS (1H-13C)Experimental nude mouse

model of human cancer

2D

Production of the [13C 2]-XXX

XXX

AlsaChim

HRMAS (1H-13C)

0

1

2

3

T 0 T +10 T +30 T +60

Times (mn)

XX

X (

mM

)

single i.v. injection of 20 mM [13C 2]-XXX

METABOLOMICS Fundamental, clinical & pre-clinical research

METABOLOMICS Fundamental, clinical & pre-clinical research

Major problem : sensitivity

1

104

0.0001

13Csignal intensity

1H signal intensity

CARMeN in vivo: 13C-NMR metabolic imaging in vivo

3T multinuclear NMR spectroscopy

METABOLOMICS Perspectives

9.4T multinuclear NMR spectroscopy

Bruker

Siemens

+cryo-probe

Bruker

13C-labelled metabolites

(GMP quality)

+

13C-labelled metabolites

+

AlsaChim

para-hydrogen induced polarization

+

Bruker

small animalimaging

medicalimaging technology transfer ?+

x6

x2

x100

x100

x4 x100

CARMeN in vivo: 13C-NMR metabolic imaging in vivo

13C-pyruvate

injected : metabolic products :

13C-lactate 13C-alanine

injected : 13C-urea

H13CO3- 13CO2

metabolic products :

http://www.imagnia.se

METABOLOMICS Perspectives

Real time metabolic imaging in vivo

Thanks for your attention