Radiolabeled antiviral drugs and antibodies as virus-specific imaging probes.
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.
Bray
Mike
M
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702, United States.
Di Mascio
Michele
M
Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, United States.
de Kok-Mercado
Fabian
F
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702, United States.
Mollura
Daniel J
DJ
Center for Infectious Disease Imaging, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, United States.
Jagoda
Elaine
E
Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States.
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
D000914:Antibodies, Viral; D000998:Antiviral Agents; D000939:Epitopes; D015335:Molecular Probes; D011849:Radioactive Tracers; D015678:Viral Structural Proteins; D013937:Thymidine Kinase; D013936:Thymidine