title: Assessment of 123I-FIAU imaging of herpes simplex viral gene expression in the treatment of glioma.
abstract: BACKGROUND
  Herpes simplex virus 1716 (HSV1716), a selectively replication competent mutant of HSV1, is under investigation as an oncolytic viral therapy in human malignant glioma. As with similar therapies, a technique for measurement of viral replication and distribution over time following virus administration is required. Imaging expression of the HSV-thymidine kinase (HSV-tk) gene offers an opportunity for non-invasive assessment of viral distribution in living subjects. This is the first study to explore the use of HSV-tk as a reporter gene and radiolabelled thymidine analogue 5-[(123)I]iodo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) uracil ((123)I-FIAU) as a marker substrate to non-invasively monitor HSV1716 replication in humans during treatment of high-grade glioma.
  
  
  METHODS
  I-FIAU brain SPECT imaging was undertaken in eight patients receiving intra-tumoural injection of HSV1716, before and after administration of the virus. Baseline images were acquired 3 days prior to virus administration and between 1 and 5 days following virus administration. Region of interest analysis was used to investigate whether there was an increase in (123)I-FIAU concentration following virus administration due to HSV-tk expression.
  
  
  RESULTS
  Increased (123)I-FIAU accumulation due to HSV-tk expression was not detected in this study. The possible explanations for this finding are explored and design options for future studies are discussed.
authors.affiliation: Institute of Neurological Sciences, Glasgow, UK. 9708003d@student.gla.ac.uk
authors.forename: Mary F
authors.initials: MF
authors.lastname: Dempsey
authors.forename: David
authors.initials: D
authors.lastname: Wyper
authors.forename: Jonathan
authors.initials: J
authors.lastname: Owens
authors.forename: Sally
authors.initials: S
authors.lastname: Pimlott
authors.forename: Vakis
authors.initials: V
authors.lastname: Papanastassiou
authors.forename: James
authors.initials: J
authors.lastname: Patterson
authors.forename: Donald M
authors.initials: DM
authors.lastname: Hadley
authors.forename: Alice
authors.initials: A
authors.lastname: Nicol
authors.forename: Roy
authors.initials: R
authors.lastname: Rampling
authors.forename: S M
authors.initials: SM
authors.lastname: Brown
mesh_terms: D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives*; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods; D005910:Glioma / Q000000981:diagnostic imaging* / Q000628:therapy / Q000821:virology*; D006801:Humans; D007457:Iodine Radioisotopes; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D018139:Simplexvirus / Q000302:isolation & purification* / Q000378:metabolism*; D013937:Thymidine Kinase / Q000032:analysis*; D014764:Viral Proteins / Q000032:analysis*; D014779:Virus Replication
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D014764:Viral Proteins; D001086:Arabinofuranosyluracil; C043457:fialuridine; C099241:thymidine kinase, Canid herpesvirus 1; D013937:Thymidine Kinase