jules bordet instituut free university brussels (ulb) patrick flamen, md, phd
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Jules Bordet InstituutFree University Brussels (ULB)
Patrick Flamen, MD, PhD
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“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
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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
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Networking> ULB (équipe cyclotron Erasme)> Européen (Munich / Amsterdam)
+++ Multidisciplinarité +++
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X-rays CT MRI PET SPECT
Nuclear Medicine
Echography
Radiology
Spectrum of Medical imaging
STRUCTURAL / MORPHOLOGICAL METABOLIC / MOLECULAR
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Imagerie MétaboliqueCaractérisation Métabolique du Nodule Pulmonaire
adenocarcinoma fibronecrotic nodule
CT
PET
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PET-CTthe new standardNuclear Oncology
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PET/CT with FDG
CT anatomy
PET metabolism
Fusion
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Rectal Cancer Staging
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Baseline PET-CT PET-CT after 2 weeks chemo
A B
chimiothérapie
Treatment Response Assessment
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Functional MRI : brain tumor
- (B) difusion-weighted imaging- (D&E) MR spectrometry
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Structural Imaging
Metabolic Imaging
Functional Imaging
Molecular Imaging
Anatomy; morphology; density
Perfusion; blood flow; contractility
Glucose ; amino acids consumption
Receptor expression; enzymatic activitygene expression; DNA
CTM
RI
PE
T
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Integrated Imaging
PET-CT
Metabolic / Molecular + Structural
MULTIMODALITY IMAGING
PET-MRI
Metabolic / Molecular / Functional
MULTIFUNCTIONAL IMAGING
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WHY ? Patient tailored medicine
• To adapt the treatment to the patient specific characteristics
Early treatment response assessment
Predicting treatment response
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Ithier Project Study Aim
• Early treatment response assessment
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Pre-Treatment 2 Months Post
43 HU 30 HU
Imaging response to Imatinib
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Imaging Response to Glivec
Cumulative Proportion Surviving (Kaplan-Meier)
Complete Censored
Group 1, Group 0,0 100 200 300 400 500 600 700
Time
-0,1
0,0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1,0
Cu
mu
lative
Pro
po
rtio
n S
urv
ivin
g
Time to treatment failure (PD on CT) n=21
P < 0.001PET respondersPET non-responders
Dr. S. Stroobants et al. (Eur J Cancer 2003)PFS according PET response 8 days after start of treatment
Stroobants et al. Eur J Cancer 2003
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Functional Imaging to Evaluate Response to Lapatinib
baseline lapatinib at surgery
Cristofanilli M, et al. Breast Cancer Res Treat. 2006;100 Supp 1:S5
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Functional MRI for Early Response measurement
M Lemort, Bordet, 2008
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V Huyge, 2008 ASCO
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Du et al. J Clin Oncol. 2007 Aug 10;25(23):3440-7
Assessment of response adjuvant chemotherapy in Metastatic breast cancer
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V Huyge, 2008 ASCO
Bone Metastatic Breast Cancer
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PET responders
PET nonresponders
PET response is related to treatment outcome
V Huyge, 2008 ASCO
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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
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FDG-PET/CT pré-traitement;
Récidive de lymphome.
FDG-PET/CT 6 mois après traitement par radioimmunothérapie avec anticorps marqués à l’Y90; rémission complète.
immuno-PET/CT; dosimétrie avec anticorps marqués au Zr89 pré-traitment.
K Muylle, 2008, Lugano
FDG-PET immuno-PET FDG response-PET
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Ga68–labeled markers PET-CT for Molecular Imaging
example: Ga68-DOTA-octreotide
> neuro-endocrine tumors (staging)> breast cancer (related to ER expression)
> prostate cancer
Ithier 2008
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GENERATOR PRODUCED PET TRACERS
Ge68-Ga68 generator
BiosynthesisGa68-DOTA-Toc (octreotide)Labeling SSR subtypes 2-5
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Retroperitoneal metastatic LN
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11 mm largest diameter
Retroperitoneal metastatic LN
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Biosynthesis Module coupled to the Ga68-generator
Automated productionLaptop directedQuality Controll GMP
Ithier Project 2008 : Ga68-radiolabeled proteins for molecular cancer imaging
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Thanks