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MAMMI Mammography with molecular imaging 102 Summary The proposed project focuses on the development of a PET prototype dedicated to the examination of breast cancer, using a gamma ray sensor based on an innovative design and the new generation of photo-detectors and scintillating crystals. The innovative features of the PEMT (Positron Emission MammoTomography) system we propose will imply a high resolution (pushed to the physical limit), higher sensitivity and lower cost. It includes integrated analogue and digital electronics through the design of an ASIC chip. The main application will be early breast cancer diagnosis and evaluation of chemotherapy response. New radio-tracer molecules will be searched for the detection and visualisation of the pharmacokinetics of breast tumours, more specifi c than glucose (FDG) for breast cancer, and based on human amino and fatty acids. Phase I Clinical trials will be performed with the new radio-tracers. A clinical multi-centric validation will be performed for the PEMT prototypes. Problem Keywords | PEMT | PET mammography | molecular imaging | breast cancer diagnosis | chemotherapy | Breast cancer is the most common non-skin cancer and the leading cause of cancer death in women. The best condition for successful breast cancer treatment is early detection. Some studies indicate that early breast cancer detection has reduced the disease mortality by about 29 %. The ability to defi ne the extent of disease, to monitor response, and to predict tumour behaviour in patients with breast cancer are therefore important public health problems. Conventional methods for breast cancer imaging like X-ray mammography, ultra-sound and Magnetic Resonance Imaging (MRI) produce morphologic and structural images, show lesions (like micro-calcifi cations), but not cancers. On the contrary, imaging methods based on Molecular Imaging show functional images, metabolism. This implies that they are much more sensitive and hence can be used to detect and locate malign tumours at an early stage. For instance, PET (Positron Emission Tomography) is a powerful tool for non-invasive molecular imaging diagnostic based on gamma ray (emitted by an isotope compound, previously administered to the patient) detection. Aim • Design and development of a dedicated low cost PET camera prototype for breast examination with an intrinsic resolution of less than 1 mm, high sensitivity, and tomographic 3D reconstruction. • Study of new and more specifi c radio-pharmaceuticals for breast cancer detection and therapy monitoring (FLT, FAS, etc.). Perform phase I clinical trials of the radio-tracers. • Clinical multi-centric validation of the new PEMT prototype. Expected results MAMMI proposes a new PET device specifi cally designed for breast cancer diagnosis and evaluation of therapy response. The dedicated breast cancer PET camera will improve the position resolution of current whole-body PET cameras (about 5 mm) and will push it to the physical limit (slightly below 1 mm). The new detector design will also have the ability to detect the depth of interaction of the gamma ray interactions within the crystal with a resolution better than 3 mm. This is an essential feature since it allows for an improvement of the fi nal image resolution by almost eliminating the parallax error present in current PET detectors. This is essential in the case of breast examination since the detector cameras are placed close to the body, to increase the sensitivity. The advantages of the new generation of photo-detectors (silicon photo-multipliers), such as their compactness, will be explored. The design of the electronics, including an ASIC, will allow an acquisition rate capability of the order of 1 MHz, with minimum dead time, to cope with the higher sensitivity. Moreover MAMMI will develop and study more specifi c than FDG radio-tracers for breast cancer diagnostic and therapy monitoring, based on human amino acids (such as FLT) and fatty acids (such as FAS). Potential applications The main application will be early breast cancer diagnosis and evaluation of chemotherapy response. New radio-tracer molecules will be searched for the detection and visualisation of the pharmacokinetics of breast tumours, more specifi c than glucose (FDG) for breast cancer, and based on human amino and fatty acids. CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Coordinator Jose M a Benlloch Consejo Superior de Investigaciones científicas IFIC – Instituto de Física Corpuscular Valencia, Spain benlloch@ific.uv.es Partners Sibylle Ziegler Klinikum Rechts der Isar der Technischen Universität München München, Germany Angels Bernabeu General equipment for Medical Imaging, S.L. Paterna, Spain PREVENTION Johann Hauer Fraunhofer-Institut für Integrierte Schaltungen Erlangen, Germany Pedro Branco DIGI-UTOPIKA LTD Lourinhã, Portugal Norberg Gunnar C-Rad Imaging AB Frösön, Sweden Anders Brahme Karolinska Institutet Stockholm, Sweden Renato A. Valdes Olmos Netherlands <strong>Cancer</strong> Institute Amsterdam, The Netherlands Project number LSHC-CT-2006-037555 EC contribution € 2 500 000 Duration 48 months Starting date 01/01/2007 Instrument STREP – SME Project website ifi c.uv.es/mammi 103
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PROJECT SYNOPSES CANCER RESEARCH PR
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CANCER RESEARCH PROJECTS FUNDED UND
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TABLE OF CONTENTS FOREWORD - CANCER
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Prevention 97 EPIC 98 EUROCADET 100
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CANCER: COMBATING A COMPLEX DISEASE
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Biology Cancer is a disease ethat t
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p53 activators ASPP Partner 5 NFkap
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Keywords | Angiogenesis | vasculoge
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Keywords | Tumour-host interactions
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Keywords | Breast | metastasis | ge
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Keywords | Identifi cation of novel
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Keywords | Systems biology | modell
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Keywords | Oncology | anticancer th
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• public health research coupled
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Expected results We will construct
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Potential applications Our DNA is u
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Microscopic examination of tissue s
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Pluripotent embryonic stem cells ar
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• Decryption of the leukaemia cel
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• identifi cation of molecular ta
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A B C LT-HSC CSC The Cancer Stem Ce
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X-ray diff raction of target drug c
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using pathway-specifi c reporter ce
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Keywords | Kinases | pediatric panc
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Keywords | Lymphangiogenesis | angi
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Keywords | Breast cancer | metastas
Page 53 and 54: Keywords | Mitosis | phosphorylatio
Page 55 and 56: Keywords | Therapy | genome | telom
Page 57 and 58: Keywords | Multiple myeloma | cance
Page 59 and 60: Keywords | p53 tumour suppressor |
Page 61 and 62: Development of eff ective anti-canc
Page 63 and 64: Coordinator Patrick A. Curmi INSERM
Page 65 and 66: Drosophila as a model system for tu
Page 67 and 68: Normal cell growth and epithelial l
Page 69 and 70: effi ciently with cancer cell proli
Page 71 and 72: A high-throughput assay of transcri
Page 73 and 74: Coordinator Ewa Sikora Nencki Insti
Page 75 and 76: Expected results The SIROCCO consor
Page 77 and 78: Keywords | Epigenetics | gene regul
Page 79 and 80: Keywords | Hereditary | tricarboxyl
Page 81 and 82: Keywords | HSV-1 | hepatocellular c
Page 83 and 84: Keywords | Apoptosis | autophagy |
Page 85 and 86: Keywords | Tumour | host | signalli
Page 87 and 88: Aetiology The uncontrolled cell gro
Page 89 and 90: Coordinator Rosalind Eeles Reader i
Page 91 and 92: The parallelogram approach in CARCI
Page 93 and 94: Keywords | Melanoma | genetics | na
Page 95 and 96: Keywords | Virus | bacteria | HPV |
Page 97 and 98: Keywords | Breast | prostate | gene
Page 99 and 100: Prevention The fact that preventing
Page 101 and 102: Coordinator Elio Riboli Imperial Co
Page 103: Coordinator Jan Willem Coebergh Joh
Page 108 and 109: BAMOD Breath-Gas Analysis for Molec
Page 110 and 111: BioCare Molecular Imaging for Biolo
Page 112 and 113: These centres of excellence will in
Page 114 and 115: Expected results Optimise the benef
Page 116 and 117: 114 Cell proliferation and apoptosi
Page 118 and 119: COBRED Colon and Breast cancer Diag
Page 120 and 121: DASIM Diagnostic Applications of Sy
Page 122 and 123: Expected results Primarily, the res
Page 124 and 125: Coordinator John A. Foekens Dept. o
Page 126 and 127: 124 Aim Drop-Top has two major obje
Page 128 and 129: Coordinator Gorka Ochoa Progenika B
Page 130 and 131: Expected results The E.E.T.-Pipelin
Page 132 and 133: e developed by eTUMOUR is likely to
Page 134 and 135: Coordinator Angel Porgador Ben-Guri
Page 136 and 137: • the design of a compact assembl
Page 138 and 139: Potential applications We believe t
Page 140 and 141: Tumor initiation, progression to ma
Page 142 and 143: MolDiag-Paca Novel Molecular Diagno
Page 144 and 145: NEMO Nano based capsule-Endoscopy w
Page 146 and 147: OVCAD Ovarian Cancer - Diagnosis of
Page 148 and 149: P-MARK Validation of recently devel
Page 150 and 151: POC4life Multiparametric quantum do
Page 152 and 153: PROMET Prostate cancer molecular-or
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Micrometastasis in the bone marrow.
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and pharmaco-kinetics studies. This
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Coordinator Raffaella Giavazzi Isti
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• Development of tools for diagno
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Treatment Two major problems when t
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Coordinator Lluis M. Mir UMR 8121 C
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Potential applications ANGIOSTOP ha
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Green-fl uorescence protein- expres
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Coordinator Robert Hawkins Universi
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Expected results The BACULOGENES pr
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descriptors of the molecules to be
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Keywords | Therapeutic vaccine | im
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Keywords | Cancer chemotherapy | dr
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Keywords | Children | cancer | leuk
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Chimaeric TCR shown in context of n
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Andrea Splendiani Leaf Bioscience s
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Coordinator Anne O’Garra The Medi
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Coordinator Jacques Bartholeyns IDM
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Structure Driven Drug Design The in
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• acquire fundamental knowledge a
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Terry Jones Victoria University of
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Potential applications The use of t
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groups and management structures. T
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T. Barbui Azienda Ospedaliera-Osped
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Keywords | Mantle cell lymphoma | t
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Keywords | Hypoxia | HIF | pericell
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Keywords | Radiation-induced compli
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Keywords | Gene therapy | adenoviru
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Keywords | Dependence receptors | a
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Keywords | Photodynamic therapy | a
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Keywords | Ovarian cancer | thymidy
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Keywords | Quality assurance | clin
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Keywords | Circadian | clocks | cel
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Keywords | Anticancer therapy | onc
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Coordinator Monika Lusky Transgene
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6 000 women over a three-year perio
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Keywords | Solid tumours | apoptosi
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Keywords | Lymphoma | leukaemia | v
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Coordinator Riccardo Dolcetti Centr
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CCPRB Cancer Control using Populati
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EPCRC The European Palliative Care
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EUROCAN+PLUS Feasibility Study for
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EUSTIR A European strategy for the
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NORMOLIFE Development of new therap
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Scientifi c Model Systems The compl
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Performance of benchmarking exercis
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• markers correlating with the im
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Indices - Keywords Indices - Partne
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● disease markers 131 ● DNA dam
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● renal 77 ● replication 219
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Bos, Nico A. 56 Boskovic, Darinka 2
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Geley, Stephan 159 Georgopoulos, Li
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Lingner, Joachim 54 Linial, Michal
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Ragno, Pia 115 Rainford, Martyn 92
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Vernos, Isabelle 22 Veronesi, Umber
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● Centre Hospitalier Universitair
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● IFOM - Fondazione Istituto FIRC
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● National University of Ireland
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● University of Bari 174 ● Univ
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