Diagnostic imaging of herpes simplex virus encephalitis using a radiolabeled antiviral drug: autoradiographic assessment in an animal model.
To develop a new approach to the diagnosis of herpes simplex encephalitis, we used a radiolabeled antiviral drug, 2'-fluoro-5-methyl-1-beta-D-arabinosyluracil labeled with carbon 14 ([14C]FMAU), as a probe for selectively imaging brain infection in a rat model by quantitative autoradiography. A high correlation was found between focal infection, as defined by immunoperoxidase viral antigen staining, and increased regional [14C]FMAU uptake in brain sections. Two potential sources of false-positive imaging were defined: high concentrations of drug in the choroid plexus because of its higher permeability compared with brain, and drug sequestration by proliferating uninfected cell populations. Our results support the soundness of the proposed strategy of using a labeled antiviral drug that is selectively phosphorylated by herpes simplex virus type 1 thymidine kinase in conjunction with scanning methods for human diagnosis, and also define some of the factors that must be taken into account when planning clinical application.
D000818:Animals; D000998:Antiviral Agents; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives*; D001345:Autoradiography; D001812:Blood-Brain Barrier; D001921:Brain / Q000000981:diagnostic imaging; D002250:Carbon Radioisotopes; D002552:Cerebral Ventricles / Q000000981:diagnostic imaging; D002831:Choroid Plexus / Q000000981:diagnostic imaging; D004660:Encephalitis / Q000000981:diagnostic imaging*; D004805:Ependyma / Q000000981:diagnostic imaging; D005260:Female; D006561:Herpes Simplex / Q000000981:diagnostic imaging*; D007700:Kinetics; D011877:Radionuclide Imaging; D051381:Rats; D014529:Uridine / Q000031:analogs & derivatives*
D000998:Antiviral Agents; D002250:Carbon Radioisotopes; D001086:Arabinofuranosyluracil; C034935:clevudine; D014529:Uridine