Medical Imaging - VUB

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Medical ImagingVicky CaveliersResearch group Medical Imaging (MIMA)In vivo Cellular and Molecular Imaging Lab (ICMI) - VUBNuclear Medicine Department - UZ Brussel

Molecular Imaging“Molecular imaging is the non-invasive visualization,characterization and measurement of biological processesat the molecular and cellular levels in humans and otherliving systems”Preclinical2Clinical7-12-2011

Bench to bedside back to bench37-12-2011

Clinical Imaging Computed Tomography orCT scan AnatomicalSingle Photon Emission TomographyPositronor PET scanSPECT scan Molecular

ICMI - Preclinical Multimodality 7-12-2011

ICMI - Preclinical Multimodality 67-12-2011

Multi-disciplinary team7 (Radio)chemistry & (Radio)pharmacy Molecular Biology, Bioengineering MD: Radiology & Nuclear Medicine MD: Cardiology Medical Physics, Mathematics, Informatics7-12-2011

In vivo Cellular and Molecular Imaging Lab (ICMI)Probe developmentidentify molecular probes select signalling label(imaging vs therapy) (radio)labeling procedures stability Biomedicalidentify molecular targets select preclinical model in vivo biodistribution andpharmacokinetics specificity and targeting clinical translation Math and Physicsimage reconstruction quantification new technologies MolecularTarget8lahoutte@gmail.com; vicky.caveliers@uzbrussel.be7-12-2011

Overview of molecular targetsOngoing research: Oncology CEA, EGFR, HER2, somatostatin receptor,amino acid transporters, hypoxia Cardiology VCAM1, LOX1 Immunology VCAM1, macrophages, dendritic cells Diabetes 9Beta cells7-12-2011

Overview of molecular probes10 Substrates (18F-FDG) Synthetic molecules (18F-FMISO) Amino acids (123I-Tyr, 18F-FMP, 18F-FET) Peptides (68Ga-octreotide)7-12-2011

Octreotide : from SPECT to PET111In-OctreoscanSPECT/CT68Ga-DOTANOCPET/CT

Overview of molecular probes Substrates (18F-FDG) Synthetic molecules (18F-FMISO) Amino acids (123I-Tyr, 18F-FMP, 18F-FET) Peptides (68Ga-octreotide) Proteins 12Nanobodies7-12-2011

Nanobodies ?CamelidaeHVHHVHCH2FcCH3Classic Monoclonal Antibody(IgG1)Single chain antibodies(IgG2 & IgG3) Heavy and light chains both chains are necessaryfor antigen-binding only heavy chains ! .fully functional forantigen-binding15 kDaNanobody The smallest functionalfragment from a naturalsingle chain AbHamers-Casterman et al., Nature, 1993

Nanobodies as probes for molecular imagingand radionuclide therapy99mTc, 111InγSPECTNanobody68Ga, 18F, 64Cu,receptorcellPETNIRF dyeFLUORESCENCEIMAGE GUIDED SURGERY177Lu, 90Y211Atα(Collaboration with Duke University)RADIONUCLIDE THERAPY147-12-2011

Imaging M2 macrophages intumor micro-environment3LL tumor WT3LL tumor MMR KO mouseconfidentialconfidential157-12-2011

anti-HER 2 lead nanobody for clinicaltranslationHer2167-12-2011

68Ga-NOTA-anti-HER2-Nanobody First in human study: Aim: To evaluate safety, biodistribution and dosimetry To compare biodistribution of 0.01, 0.1 and 1mg To show targeting in HER2 breast cancer Study population Female patients 18y with locally advanced or metastatic HER2 breast carcinoma Study groups 5 patients for each dose (0.01, 0.1 and 1mg)

68Ga-NOTA-anti-HER2-Nanobody Exclusion criteria Pregnancy Anti-HER2 treatment Abnormal liver or kidney function Patients with active infectionsStudy procedure Single IV injection of 68Ga-NOTA-anti-HER2-Nanobody Total body PET/CT scan @ 1h and 2h p.i. (2x25 min) No contrast injections Clinical exam, blood sampling and urine analysis

Futur focus New imaging technologies (PET/MRI,.) andreconstruction algorithms 19Molecular probe development: Further extend Nanobody platform GMP radiopharmaceutical productionTranslational research !7-12-2011

AcknowledgementsProf Tony Lahoutte, PhDProf Michel Defrise, PhDProf Vicky Caveliers, PhDProf Axel Bossuyt, PhD20Post-doc researchersCatarina Xavier, PhDNick Devoogdt, PhDIlse Vaneycken, PhDMarleen Keyaerts, PhDSophie Hernot, PhDJan Heemskerk, PhDChristophe Cloquet, PhDPhD candidatesLode GoethalsInneke WillekensMatthias D’huyvetterSam MassaJens De VosAnneleen BlykersReema Al-AifariCindy Peleman, Laboratory technicianCarlien Geldof, Executive research assistant7-12-2011

Research group Medical Imaging (MIMA) In vivo Cellular and Molecular Imaging Lab (ICMI) - VUB Nuclear Medicine Department - UZ Brussel. 2 7-12-2011 . Medical Physics, Mathematics, Informatics. 8 7-12-2011 In vivo Cellular and Molecular Imaging Lab (ICMI) Probe development identify molecular probes

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