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      Fusion of [ 18F]FDG PET with Fluorescence Diffuse Optical Tomography to Improve Validation of Probes and Tumor Imaging

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          Abstract

          Purpose

          Given the progress of fluorescence diffuse optical tomography (fDOT) technology, here, we study the additional benefits provided by multimodal PET/fDOT imaging by comparing the biodistribution of 2-deoxy-2-[ 18F]fluoro- d-glucose ([ 18F]FDG) in tumors with three fluorescent probes: a glucose analog, a protease activatable optical probe, and a ligand of αvβ3 integrin.

          Procedures

          Sequential fDOT/PET/computed tomography (CT) imaging of mice was performed with a custom multimodal mouse support that allows the subject to be transferred between the fDOT and the PET/CT scanners. Experiments were performed in xenografted tumor models derived from the human breast cancer line MDA-MB 231 and compared to ex vivo analysis.

          Results

          The three-dimensional signals showed that the fluorescent glucose analog is not colocalized with [ 18F]FDG, raising questions about its use as a surrogate probe of the PET tracer. Fusion of [ 18F]FDG with the other fluorescent probes showed evidence of high variability both for the protease activity and the αvβ3 integrin expression during tumor growth.

          Conclusion

          The added value of hybrid PET/fDOT over the two modalities was demonstrated for cross-validation of probes and for better characterization of tumor models.

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          Most cited references34

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          Requirement of vascular integrin alpha v beta 3 for angiogenesis.

          Angiogenesis depends on the adhesive interactions of vascular cells. The adhesion receptor integrin alpha v beta 3 was identified as a marker of angiogenic vascular tissue. Integrin alpha v beta 3 was expressed on blood vessels in human wound granulation tissue but not in normal skin, and it showed a fourfold increase in expression during angiogenesis on the chick chorioallantoic membrane. In the latter assay, a monoclonal antibody to alpha v beta 3 blocked angiogenesis induced by basic fibroblast growth factor, tumor necrosis factor-alpha, and human melanoma fragments but had no effect on preexisting vessels. These findings suggest that alpha v beta 3 may be a useful therapeutic target for diseases characterized by neovascularization.
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            In vivo imaging of tumors with protease-activated near-infrared fluorescent probes.

            We have developed a method to image tumor-associated lysosomal protease activity in a xenograft mouse model in vivo using autoquenched near-infrared fluorescence (NIRF) probes. NIRF probes were bound to a long circulating graft copolymer consisting of poly-L-lysine and methoxypolyethylene glycol succinate. Following intravenous injection, the NIRF probe carrier accumulated in solid tumors due to its long circulation time and leakage through tumor neovasculature. Intratumoral NIRF signal was generated by lysosomal proteases in tumor cells that cleave the macromolecule, thereby releasing previously quenched fluorochrome. In vivo imaging showed a 12-fold increase in NIRF signal, allowing the detection of tumors with submillimeter-sized diameters. This strategy can be used to detect such early stage tumors in vivo and to probe for specific enzyme activity.
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              Molecular imaging in drug development.

              Molecular imaging can allow the non-invasive assessment of biological and biochemical processes in living subjects. Such technologies therefore have the potential to enhance our understanding of disease and drug activity during preclinical and clinical drug development, which could aid decisions to select candidates that seem most likely to be successful or to halt the development of drugs that seem likely to ultimately fail. Here, with an emphasis on oncology, we review the applications of molecular imaging in drug development, highlighting successes and identifying key challenges that need to be addressed for successful integration of molecular imaging into the drug development process.
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                Author and article information

                Contributors
                +33-1-69867766 , +33-1-69867786 , frederic.duconge@cea.fr
                Journal
                Mol Imaging Biol
                Mol Imaging Biol
                Molecular Imaging and Biology
                Springer-Verlag (New York )
                1536-1632
                1860-2002
                28 August 2012
                28 August 2012
                June 2013
                : 15
                : 3
                : 316-325
                Affiliations
                [ ]CEA, Institut d’Imagerie Biomédicale, Service Hospitalier Frédéric Joliot, Orsay Cedex, France
                [ ]INSERM U1023, Laboratoire d’Imagerie Moléculaire Expérimentale, Orsay Cedex, France
                [ ]Université Paris Sud, Orsay Cedex, France
                [ ]CEA, Institut de Biologie et de Technologies de Saclay, Service d’Ingénierie Moléculaire de Protéines, Gif/Yvette Cedex, France
                Article
                581
                10.1007/s11307-012-0581-z
                3647087
                22927057
                cb0526fb-e12e-4988-a9d6-7f97d839fde8
                © The Author(s) 2012
                History
                Categories
                Research Article
                Custom metadata
                © World Molecular Imaging Society 2013

                Molecular biology
                fluorescence molecular tomography,fluorescence diffuse optical tomography,positron-emission tomography,small-animal multimodal imaging,cancer

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