Imaging in vivo herpes simplex virus thymidine kinase gene transfer to tumour-bearing rodents using positron emission tomography and [F-18]FHPG

Radiolabelled ganciclovir analogues have shown promise as imaging agents to detect herpes simplex virus thymidine kinase (HSVtk) expression. This stud y evaluated the use of positron emission tomography (PET) imaging with 9-[( 3-[F-18]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([F-18]FHPG) to assess ge ne transfer into tumours. HSVtk-positive and HSVtk-negative cell lines were first treated in vitro with [F-18]FHPG. To assess the efficacy of PET in d etecting HSVtk expression following in vivo gene transfer, mice were inject ed intravenously with an adenovirus encoding HSVtk (Ad.HSVtk), a control ve ctor (Ad.Bgl2) or saline. Subcutaneous human glioma xenografts were grown i n mice and treated by direct injection of Ad.HSVtk or Ad.Bgl2. Imaging was performed 48 h after transduction. Similar experiments were performed using Fischer rats implanted with syngeneic tumours. The presence of the HSVtk p rotein was confirmed by immunohistochemistry. Biodistribution studies were also obtained in 14 naive mice. In vitro studies showed high and specific u ptake of [F-18]FHPG in HSVtk-positive cell lines, with an uptake ratio of u p to 2.7.1. PET imaging and direct counting of major organs demonstrated HS Vtk-specific tracer retention. In mice, HSVtk-positive tumours retained 3.4 % dose/gram as compared to 0.6% for control tumours (P=0.03). They were cle arly seen on the PET images as early as 100 min post injection. Similar res ults were obtained with syngeneic rat tumours. Biodistribution studies demo nstrated the rapid distribution and clearance of the tracer in all major or gans. Our results demonstrate that PET imaging of HSVtk gene transfer to tu mours is feasible and is highly specific for HSVtk expression.