Molecular Imaging - Institut Jules Bordet Instituut

Patrick Flamen, MD, PhD
Jules Bordet Instituut
Free University Brussels (ULB)
“Integrated Molecular Imaging in
Oncology using PET-CT (radiolabeled
peptides) and MRI (DCE-MRI and MRS).”
• Molecular Imaging:


What ? Why ? How ?
Positron Emission Tomography
Functional MRI
• Integration



imaging information (PET-MRI)
translational and clinical research activities
Clinical team (nuc med / functional radiology)
• Radiolabeled biomarkers (peptides)

Ga68-labeling
The Ultimate Goal of Molecular Imaging
•
Patient tailored medicine
 To adapt the treatment to the patient specific
characteristics
» From : one treatment for all
» To: one patient one treatment
This requires the knowledge of the underlying
molecular defects of the cancer
+++ Multidisciplinarité +++
Networking
> ULB (équipe cyclotron Erasme)
> Européen (Munich / Amsterdam)
Spectrum of Medical imaging
Radiology
X-rays
CT
MRI
Nuclear Medicine
Echography
STRUCTURAL / MORPHOLOGICAL
PET
SPECT
METABOLIC / MOLECULAR
Imagerie Métabolique
Caractérisation Métabolique du Nodule Pulmonaire
CT
PET
adenocarcinoma
fibronecrotic nodule
PET-CT
the new standard
Nuclear Oncology
PET/CT with FDG
CT
anatomy
PET
metabolism
Fusion
Rectal Cancer Staging
Treatment Response Assessment
B
A
chimiothérapie
Baseline PET-CT
PET-CT after 2 weeks chemo
Functional MRI : brain tumor
- (B) difusion-weighted imaging
- (D&E) MR spectrometry
CT
Structural Imaging
Anatomy; morphology; density
MRI   
Functional Imaging
Perfusion; blood flow; contractility
Metabolic Imaging
Glucose ; amino acids consumption
PET
Molecular Imaging
Receptor expression; enzymatic activity
gene expression; DNA
Integrated Imaging
PET-CT
Metabolic / Molecular + Structural
MULTIMODALITY IMAGING
PET-MRI
Metabolic / Molecular / Functional
MULTIFUNCTIONAL IMAGING
WHY ?
Patient tailored medicine
•
To adapt the treatment to the patient specific
characteristics
 Early treatment response assessment
 Predicting treatment response
Ithier Project Study Aim
•
Early treatment response assessment
Imaging response to Imatinib
30 HU
43 HU
Pre-Treatment
2 Months Post
Imaging Response to Glivec
Dr. S. Stroobants et al. (Eur J Cancer 2003)
PFS according PET response 8 days after start of treatment
Time to treatment failure (PD on CT) n=21
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PET responders
PET non-responders
P < 0.001
Stroobants et al. Eur J Cancer 2003
Functional Imaging to Evaluate Response
to Lapatinib
baseline
lapatinib
at surgery
Cristofanilli M, et al. Breast Cancer Res Treat. 2006;100 Supp 1:S5
Functional MRI for Early Response measurement
M Lemort, Bordet, 2008
V Huyge, 2008 ASCO
Assessment of response adjuvant chemotherapy in
Metastatic breast cancer
Du et al. J Clin Oncol. 2007 Aug 10;25(23):3440-7
Bone Metastatic Breast Cancer
V Huyge, 2008 ASCO
PET response is related to treatment outcome
PET non
responders
PET
responders
V Huyge, 2008 ASCO
Ithier Project Study Aim
Predicting response to a targeted treatment
By means of the identification the molecular target of
the drug
Examples:
 her2/neu breast cancer receptor imaging
» predicting Herceptine treatment
» Radiolabeled trastuzumab (Zirconium-89 ? )
 Hormone receptor imaging
» predicting response to anti-hormonal treatment
FDG-PET/CT pré-traitement;
Récidive de lymphome.
FDG-PET
immuno-PET/CT; dosimétrie avec
anticorps marqués au Zr89 prétraitment.
immuno-PET
FDG-PET/CT 6 mois après
traitement par radioimmunothérapie
avec anticorps marqués à l’Y90;
rémission complète.
FDG response-PET
K Muylle, 2008, Lugano
Ithier 2008
Ga68–labeled markers
PET-CT for Molecular Imaging
example: Ga68-DOTA-octreotide
> neuro-endocrine tumors (staging)
> breast cancer (related to ER expression)
> prostate cancer
GENERATOR PRODUCED PET TRACERS
Ge68-Ga68
generator
Biosynthesis
Ga68-DOTA-Toc (octreotide)
Labeling SSR subtypes 2-5
Retroperitoneal metastatic LN
Retroperitoneal metastatic LN
11 mm largest diameter
Biosynthesis Module coupled to the Ga68-generator
Automated production
Laptop directed
Quality Controll
GMP
Ithier Project 2008 : Ga68-radiolabeled proteins for molecular cancer imaging
Thanks