Workpackage no 6: Cancer imaging with focus on breast cancer: Late results. Anikitos Garofalakis CEA INSERM U1023, Orsay

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1 Workpackage no 6: Cancer imaging with focus on breast cancer: Late results Anikitos Garofalakis CEA INSERM U1023, Orsay

2 Overview Deliverables Multimodality FMT XCT Recent results Conclusions Perspectives

3 Deliverables Probes and Models To develop and characterize molecular probes (Deliverable 6.1) Commercial probes Aptamers Nanomicelles for in vivo imaging Prepare and characterize mammary cancer animal models (Deliverables 6.2, 6.3, 6.4) Xenografts MDA MB 231 MCF 7 Spontaneous tumours PymT

4 Deliverables Probes and Models To develop and characterize molecular probes (Deliverable 6.1) Commercial probes Aptamers Nanomicelles Prepare and characterize mammary cancer animal models (Deliverables 6.2, 6.3, 6.4) Xenografts MDA MB 231 MCF 7 Spontaneous tumours PymT to HMGU

5 Deliverables Evaluation of FMT XCT Study and report the quantitative accuracy of of FMT alone and and FMT XCT in in resolving tumors tumors (mo. 36) (mo. (Deliverable 36) (Deliverable 6.5) 6.5) Preclinical imaging in CEA- Orsay SPECT/CT Stand alone Micro PET Micro PET/CT Bioluminescence Fluobeam Cellvizio endoscope Fluorescence Molecular Tomography

6 CEA LIME multimodal approach PET/CT FMT t(min)

7 Results on the quantification Oligonucleotide + Oligonuceotide 1000 PET/CT FMT/CT pmoles by PET CT PET volume fdot volume CT volume 0, fdot (a.u.) Sensitivity limit ~ 1 pmoles, 5nM(C) Garofalakis A. et al, In vivo validation of free space fluorescence tomography using nuclear imaging, Optics Letters, 2010

8 FMT PET as a tool of evaluating new probes FDG,Glucose analogue Radionuclide F 18 Fluorophore F 18 [FDG] + 2DG IRDye 800(Licor)

9 FMT PET as a tool of evaluating new probes a b c d FDG-PET 3D Optical (2-DG) FDG/2-DG e f g h FDG-PET 3D Optical (2-DG) FDG/2-DG i j k l Glut-1 2 mm 2D Optical (2-DG) Glut-1/2-DG White light optical Optical analogue is not co localized with the nuclear reference probe IRDye is maybe connected to GLUT 1 receptors (Hypoxia)

10 FMT PET as a tool of enhancing tumor information Prosense680 (PerkinElmer) Cathepsin activity + [ 18 F]FDG Glucose consumption FMT/PET imaging pmoles 25 Overlap with FDG No overlap with FDG mm mm 3 Co localisation isevolved with the tumor size

11 6.6 Study and report cancer detection performance in various organs (mo. 40) 6.7 Report the overall imaging performance. (mo.42) Conclusions Development of several animal models for cancer imaging Development of custom made probes Multimodal FMT/PET technique based on the sequential imaging Evaluation of new optical probes Complementary molecular information

12 Future directions Bimodal probes, activatables et theragnostic Double labelling hybridization drugs nanoparticle aptamer PEG

13 Future directions (2) Fluorescently labeled Apta-nano radiolabeled Apta-nano Diagnostic and staging using whole body imaging (PET, SPECT, MRI ) Imaging-guided surgery or biopsy 26 octobre 2012 SHFJ 27 JUIN 2012 PAGE 13

14 Aknowledgements CEA INSERM U1023 Albertine Dubois, Dr(former member) Xiao Tong, Phd student Benoît Thézé Bertrand Tavitian, Prof Frédéric Ducongé, Dr CEA Bertrand Czarny, Technician (Chemistry Laboratory for life sciences CEA) Bertrand Kühnast, Dr Frederic Dollé, Dr Commercial partner Digisense, SA Bourget du Lac CEDEX, France TomoFluo3D