Effect of acyclovir on the uptake of ¹³¹ I‐labelled 1‐(2′fluoro‐2′‐deoxy‐βD‐D‐arabinofuranosyl)‐5‐lodouracil in herpes infected cells

Abstract

Selective uptake of nucleoside analogues by herpes simplex virus infected cells may serve as the basis for a specific non-invasive diagnostic test for herpes simplex encephalitis. We have examined the effect of acyclovir on the selective uptake of [131I] 1-(2'-fluoro-2'-deoxy-beta-D-arabinofuranosyl)-5-iodouracil in herpes simplex virus infected primary rabbit kidney cells. Infected cells treated with acyclovir continued to concentrate [131I] 1-(2'-fluoro-2'-deoxy-beta-D-arabinofuranosyl)-5-iodouracil for up to 24 h after the addition of the antiviral agent. These results indicated that therapy with acyclovir for as long as 24 h would not prevent the selective trapping of nucleoside analogues. This has important implications for the use of nucleoside analogues in diagnostic brain scans to detect herpes simplex encephalitis.

Altered in vitro uptake of the radiolabelled antiviral imaging “probe” e‐5‐(2‐125iodovinyl)‐2′‐deoxyuridine following administration of acyclovir

“…This study suggests that acyclovir pretreatment may compromise the effectiveness of neuroradiological imaging with rIVDU. However, Tovell et al [1987] in an analogous in vitro study using 1311 labelled 1-(2'fluoro-2'-deoxy-B-D-arabinofuranosyl)-5-iodouracil (FIAU), found neither enhancement nor inhibition of uptake of this radioprobe in the presence of acyclovir (at 1 p,g/ml). FIAU, in common with rIVDU, is phosphorylated only within virus-infected cells, and this phosphorylation appears to be dependent on virus-specified TK [Tovell et al, 19871.…”

Scintigraphic Imaging of HSVtk Expression in Gene Therapy

“…A good correlation was found between in-vivo [ 124 I]FIAU accumulation and in-vitro ganciclovir sensitivity. In-vitro, treatment with the antiviral agent acyclovir could not prevent the selective trapping of [ 131 I]FIAU in HSV infected rabbit kidney cells [51], indicating that acyclovir treatment does not need to be interrupted for scintigraphic imaging with radiolabeled FIAU. Deng et al showed that the therapeutic effect of ganciclovir treatment of mice bearing a subcutaneous HSVtk-expressing tumor could be monitored with [ 131 I]FIAU and planar gamma imaging [44].…”