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Radiopharmaceuticals for Imaging in Oncology with Special Emphasis on Positron-Emitting Agents

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Nuclear Oncology

Abstract

Over the past twenty years, nuclear imaging has arguably had more impact on oncology than any other field of medicine, particularly due to the ability of nuclear imaging to provide functional information about tumors rather than anatomical images alone. As a result, the design, synthesis, and development of cancer-targeted radiopharmaceuticals, particularly those for positron emission tomography (PET), have become areas of significant and intense investigation. A wide variety of factors must be considered in the design and synthesis of a novel, effective cancer-targeted radiopharmaceutical, including the choice of a cancer-specific molecular target capable of producing high tumor-to-background contrast, the creation of a targeting molecule able to bind the target with high specificity and affinity, the selection of a radioisotope appropriate for the pharmacokinetics of the targeting molecule, the methodology for incorporating the radiolabel into the targeting molecule, and the synthetic strategy for radiolabeling the targeting molecule. By a wide margin, the most commonly employed PET tracer in oncology is [18F]-fluorodeoxyglucose ([18F]FDG), an FDA-approved radiopharmaceutical that concentrates in tumors due to the tendency of many neoplasms to possess up-regulated glycolytic pathways and over-expressed glucose transporters. However, [18F]FDG is far from the only cancer-targeted PET agent: a large number of effective radiopharmaceuticals have been developed to target other differences between neoplastic and normal tissue. Indeed, radiopharmaceuticals have been created to target over-expressed cell surface biomarkers (e.g. HER2/neu or PSMA), up-regulated processes in tumor cells (e.g. nucleic acid metabolism or amino acid transport), and traits of the tumor microenvironment (e.g. acidosis or hypoxia). In the following chapter, the fundamental principles of the design, synthesis, and development of small molecule, peptidic, and antibody-based radiopharmaceuticals will be presented along with a wide-ranging review of the most promising emerging cancer-targeted PET and SPECT imaging agents.

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Authors and Affiliations

  1. Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA

    Brian M. Zeglis PhD, Jason P. Holland PhD, Artem Y. Lebedev PhD, Melchor V. Cantorias PhD & Jason S. Lewis PhD

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  1. Brian M. Zeglis PhD
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  2. Jason P. Holland PhD
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  4. Melchor V. Cantorias PhD
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  5. Jason S. Lewis PhD
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Correspondence to Jason S. Lewis PhD .

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  1. Dept. Radiology, Div. Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, York Ave. 1275, New York, 10021, New York, USA

    H. William Strauss

  2. Centro Regionale di Medicina Nucleare, Universita di Pisa, Via Roma 67, Pisa, 56100, Italy

    Giuliano Mariani

  3. Centro Regionale di Medicina Nucleare, Universita di Pisa, Via Roma 67, Pisa, 56100, Italy

    Duccio Volterrani

  4. Cancer Center, Department of Radiology, Memorial Sloan-Kettering, York Ave. 1275, New York, 10021, New York, USA

    Steven M. Larson

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Zeglis, B.M., Holland, J.P., Lebedev, A.Y., Cantorias, M.V., Lewis, J.S. (2013). Radiopharmaceuticals for Imaging in Oncology with Special Emphasis on Positron-Emitting Agents. In: Strauss, H., Mariani, G., Volterrani, D., Larson, S. (eds) Nuclear Oncology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-48894-3_3

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