title: Radiolabeled antiviral drugs and antibodies as virus-specific imaging probes.
abstract: A number of small-molecule drugs inhibit viral replication by binding directly to virion structural proteins or to the active site of a viral enzyme, or are chemically modified by a viral enzyme before inhibiting a downstream process. Similarly, antibodies used to prevent or treat viral infections attach to epitopes on virions or on viral proteins expressed on the surface of infected cells. Such drugs and antibodies can therefore be thought of as probes for the detection of viral infections, suggesting that they might be used as radiolabeled tracers to visualize sites of viral replication by single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. A current example of this approach is the PET imaging of herpes simplex virus infections, in which the viral thymidine kinase phosphorylates radiolabeled thymidine analogues, trapping them within infected cells. One of many possible future applications might be the use of a radiolabeled hepatitis C protease inhibitor to image infection in animals or humans and provide a quantitative measure of viral burden. This article reviews the basic features of radionuclide imaging and the characteristics of ideal tracer molecules, and discusses how antiviral drugs and antibodies could be evaluated for their suitability as virus-specific imaging probes. The use of labeled drugs as low-dose tracers would provide an alternative application for compounds that have failed to advance to clinical use because of insufficient in vivo potency, an unsuitable pharmacokinetic profile or hepato- or nephrotoxicity.
authors: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702, United States.
authors: Mike
authors: M
authors: Bray
authors: Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, United States.
authors: Michele
authors: M
authors: Di Mascio
authors: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702, United States.
authors: Fabian
authors: F
authors: de Kok-Mercado
authors: Center for Infectious Disease Imaging, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, United States.
authors: Daniel J
authors: DJ
authors: Mollura
authors: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States.
authors: Elaine
authors: E
authors: Jagoda
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology / Q000378:metabolism; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D000939:Epitopes / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D015335:Molecular Probes; D049268:Positron-Emission Tomography / Q000379:methods; D011849:Radioactive Tracers; D011877:Radionuclide Imaging; D013936:Thymidine / Q000031:analogs & derivatives; D013937:Thymidine Kinase / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D015678:Viral Structural Proteins / Q000378:metabolism*; D014771:Virion / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D014777:Virus Diseases / Q000000981:diagnostic imaging* / Q000821:virology; D014779:Virus Replication; D014780:Viruses / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D000939:Epitopes; D015335:Molecular Probes; D011849:Radioactive Tracers; D015678:Viral Structural Proteins; D013937:Thymidine Kinase; D013936:Thymidine