Journal Article

Comparison of 18FFHPG and 124/125IFIAU for imaging herpes simplex virus type 1 thymidine kinase gene expression

Haubner, Roland, Scheunemann, Matthias, Hauses, Martin, Avril, Norbert, Noll, Steffi, Schackert, Hans K., Brust, Peter, Anton, Martina, Haberkorn, Uwe, Schackert, Gabriele, Friedrich, Anne, Koufaki, Olga-Niki, Noll, Bernhard, Johannsen, Bernd

2001

Overview

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.

• Publisher: Springer,Springer Nature B.V
• Subject: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Animals / Antiviral Agents - pharmacology / Applied cell therapy and gene therapy / Arabinofuranosyluracil - analogs & derivatives / Arabinofuranosyluracil - pharmacokinetics / Biological and medical sciences / Cell Line / Cells, Cultured / Endocrine glands. Genital system. Mammary gland / Enzyme Inhibitors - pharmacology / Ganciclovir - analogs & derivatives / Ganciclovir - pharmacokinetics / Gene Expression Regulation, Enzymologic - genetics / Gene Expression Regulation, Viral - genetics / Genetic Vectors / Herpesvirus 1, Human - enzymology / Herpesvirus 1, Human - genetics / Investigative techniques, diagnostic techniques (general aspects) / Medical sciences / Mice / Mice, Inbred BALB C / Radionuclide investigations / Radiopharmaceuticals - pharmacokinetics / Thymidine Kinase - antagonists & inhibitors / Thymidine Kinase - biosynthesis / Thymidine Kinase - genetics / Tissue Distribution / Transfection / Transfusions. Complications. Transfusion reactions. Cell and gene therapy / Transgenes - genetics