Comparison of [18F]FHPG and [124/125I]FIAU for imaging herpes simplex virus type 1 thymidine kinase gene expression
| Autor: | Steffi Noll, Hans K. Schackert, Bernd Johannsen, Norbert Avril, Roland Haubner, Peter Brust, Anne Friedrich, Uwe Haberkorn, Martina Anton, Olga Niki Koufaki, Bernhard Noll, Matthias Scheunemann, Martin Hauses, Gabriele Schackert |
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| Rok vydání: | 2001 |
| Předmět: |
Gene Expression Regulation
Viral Biodistribution Guanine Genetic Vectors Herpesvirus 1 Human Transfection Antiviral Agents Thymidine Kinase Gene Expression Regulation Enzymologic Cell Line chemistry.chemical_compound Mice In vivo Animals Radiology Nuclear Medicine and imaging Uracil nucleoside Tissue Distribution Transgenes Enzyme Inhibitors Ganciclovir Cells Cultured Reporter gene Mice Inbred BALB C Arabinofuranosyluracil Uracil General Medicine Virology Molecular biology In vitro chemistry Thymidine kinase Radiopharmaceuticals |
| Zdroj: | European journal of nuclear medicine. 28(6) |
| ISSN: | 0340-6997 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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