Transcript Material and Methods - Institut Jules Bordet
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).”
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Molecular Imaging:
What ? Why ? How ?
Positron Emission Tomography
Functional MRI
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Integration
imaging information (PET-MRI)
translational and clinical research activities Clinical team (nuc med / functional radiology)
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Radiolabeled biomarkers (peptides)
Ga68-labeling
The Ultimate Goal of Molecular Imaging
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Patient tailored medicine
To adapt the treatment to the patient specific characteristics
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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)
X-rays CT
Spectrum of Medical imaging
Radiology Nuclear Medicine MRI Echography PET SPECT STRUCTURAL / MORPHOLOGICAL 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 PET anatomy metabolism Fusion
Rectal Cancer Staging
Treatment Response Assessment
A B chimiothérapie Baseline PET-CT PET-CT after 2 weeks chemo
Functional MRI : brain tumor
- (B) difusion-weighted imaging - (D&E) MR spectrometry
Structural Imaging
Anatomy; morphology; density
Functional Imaging
Perfusion; blood flow; contractility
Metabolic Imaging
Glucose ; amino acids consumption
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
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To adapt the treatment to the patient specific characteristics
Early treatment response assessment
Predicting treatment response
Ithier Project Study Aim
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Early treatment response assessment
Imaging response to Imatinib
43 HU 30 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 0 PET responders PET non-responders o o 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
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predicting Herceptine treatment Radiolabeled trastuzumab (Zirconium-89 ? )
Hormone receptor imaging
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predicting response to anti-hormonal treatment
FDG-PET/CT pré-traitement; Récidive de lymphome.
immuno-PET/CT; dosimétrie avec anticorps marqués au Zr89 pré traitment.
FDG-PET/CT 6 mois après traitement par radioimmunothérapie avec anticorps marqués à l’Y90; rémission complète.
FDG-PET immuno-PET 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