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Quantitative autoradiographic mapping of herpes simplex virus encephalitis with a radiolabeled antiviral drug

Journal Article · · Science (Washington, D.C.); (United States)
; ; ; ; ; ;

2'-Fluoro-5-methyl-1-..beta..-D-arabinosyluracil (FMAU) labeled with carbon-14 was used to image herpes simplex virus type 1-infected regions of rat brain by quantitative autoradiography. FMAU is a potent antiviral pyrimidine nucleoside which is selectively phosphorylated by virus-coded thymidine kinase. When the labeled FMAU was administered 6 hours before the rats were killed, the selective uptake and concentration of the drug and its metabolites by infected cells (defined by immunoperoxidase staining of viral antigens) allowed quantitative definition and mapping of HSV-1-infected structures in autoradiograms of brain sections. These results shown that quantitative autoradiography can be used to characterize the local metabolism of antiviral drugs by infected cells in vivo. They also suggest that the selective uptake of drugs that exploit viral thymidine kinase for their antiviral effect can, by appropriate labeling, be used in conjunction with clinical neuroimaging techniques to define infected regions of human brain, thereby providing a new approach to the diagnosis of herpes encephalitis in man.

Research Organization:
Sloan-Kettering Inst., New York, NY
OSTI ID:
6529072
Journal Information:
Science (Washington, D.C.); (United States), Journal Name: Science (Washington, D.C.); (United States) Vol. 217; ISSN SCIEA
Country of Publication:
United States
Language:
English

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Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
ANTIMETABOLITES
AUTORADIOGRAPHY
AZINES
BODY
BRAIN
CARBON 14 COMPOUNDS
CENTRAL NERVOUS SYSTEM
DIAGNOSIS
DISEASES
DISTRIBUTION
DRUGS
ENCEPHALITIS
FLUOROURACILS
HERPES SIMPLEX
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INFECTIOUS DISEASES
LABELLED COMPOUNDS
MAMMALS
METABOLISM
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIMIDINES
RATS
RODENTS
SKIN DISEASES
TISSUE DISTRIBUTION
URACILS
VERTEBRATES
VIRAL DISEASES