Comparison of [18F]FHPG and [124/125I]FIAU for imaging herpes simplex virus type 1 thymidine kinase gene expression.

Abstract

Various radiotracers based on uracil nucleosides (e.g. [124I]2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil, [124I]FIAU) and acycloguanosine derivatives (e.g. [18F]9-[(3-fluoro-1-hydroxy-2-propoxy) methyl] guanine, [18F]FHPG) have been proposed for the non-invasive imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene expression. However, these radiotracers have been evaluated in different in vitro and in vivo models, precluding a direct comparison. Therefore, we directly compared [18F]FHPG and radioiodinated FIAU to assess their potential for PET imaging of transgene expression. The uptake of [125I]FIAU, [18F]FHPG and [3H]acyclovir was determined in vitro using four different HSV1-tk expressing cell lines and their respective negative controls. The in vitro tracer uptake was generally low in non-transduced parental cell lines. In HSV1-tk expressing cells, [3H]acyclovir showed approximately a twofold higher tracer accumulation, the [18F]FHPG uptake increased by about sixfold and the [125I]FIAU accumulation increased by about 28-fold after 120-min incubation of T1115 human glioblastoma cells. Similar results were found in the other cell lines. In addition, biodistribution and positron emission tomography (PET) studies with [18F]FHPG and [124/125I]FIAU were carried out in tumour-bearing BALB/c mice. Significantly higher specific accumulation of radioactivity was found for [125I]FIAU compared with [18F]FHPG. The ratio of specific tracer accumulation between [125I]FIAU and [18F]FHPG increased from 21 (30 min p.i.) to 119 (4 h p.i.). PET imaging, using [124I]FIAU, clearly visualised and delineated HSV1-tk expressing tumours, whereas only a negligible uptake of [18F]FHPG was observed. This study demonstrated that in vitro and in vivo, the radioiodinated uracil nucleoside FIAU has a significantly higher specific accumulation than the acycloguanosine derivative [18F]FHPG. This suggests that [124I]FIAU should be the preferred reporter probe for PET imaging of HSV1-tk gene expression. Thus, further attempts to develop suitable PET tracers for the assessment of HSV1-tk gene expression should also focus on 18F-labelled uracil derivatives.

• Authors: P Brust, R Haubner, A Friedrich, M Scheunemann, M Anton, O N Koufaki, M Hauses, S Noll, B Noll, U Haberkorn, G Schackert, H K Schackert, N Avril, B Johannsen
• Journal: European journal of nuclear medicine (Eur J Nucl Med) Vol. 28 Issue 6 Pg. 721-9 (Jun 2001) ISSN: 0340-6997 [Print] Germany
• PMID: 11440032 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 9-((3-fluoro-1-hydroxy-2-propoxy)methyl)guanine
• Antiviral Agents
• Enzyme Inhibitors
• Radiopharmaceuticals
• Arabinofuranosyluracil
• fialuridine
• Thymidine Kinase
• Ganciclovir

Topics

• Animals
• Antiviral Agents (pharmacology)
• Arabinofuranosyluracil (analogs & derivatives, pharmacokinetics)
• Cell Line
• Cells, Cultured
• Enzyme Inhibitors (pharmacology)
• Ganciclovir (analogs & derivatives, pharmacokinetics)
• Gene Expression Regulation, Enzymologic (genetics)
• Gene Expression Regulation, Viral (genetics)
• Genetic Vectors
• Herpesvirus 1, Human (enzymology, genetics)
• Mice
• Mice, Inbred BALB C
• Radiopharmaceuticals (pharmacokinetics)
• Thymidine Kinase (antagonists & inhibitors, biosynthesis, genetics)
• Tissue Distribution
• Transfection
• Transgenes (genetics)