Assessment of 123I-FIAU imaging of herpes simplex viral gene expression in the treatment of glioma.
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.
Dempsey
Mary F
MF
Institute of Neurological Sciences, Glasgow, UK. 9708003d@student.gla.ac.uk
Wyper
David
D
Owens
Jonathan
J
Pimlott
Sally
S
Papanastassiou
Vakis
V
Patterson
James
J
Hadley
Donald M
DM
Nicol
Alice
A
Rampling
Roy
R
Brown
S M
SM
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
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D014764:Viral Proteins; D001086:Arabinofuranosyluracil; C043457:fialuridine; C099241:thymidine kinase, Canid herpesvirus 1; D013937:Thymidine Kinase