Comparison of [18F]FHPG and [124/125I]FIAU for imaging herpes simplex virus type 1 thymidine kinase gene expression.
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.
Brust
P
P
Institute of Bioinorganic and Radiopharmaceutical Chemistry, Forschungszentrum, Rossendorf, Germany.
Haubner
R
R
Friedrich
A
A
Scheunemann
M
M
Anton
M
M
Koufaki
O N
ON
Hauses
M
M
Noll
S
S
Noll
B
B
Haberkorn
U
U
Schackert
G
G
Schackert
H K
HK
Avril
N
N
Johannsen
B
B
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002460:Cell Line; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D014018:Tissue Distribution; D014162:Transfection; D019076:Transgenes / Q000235:genetics
C104325:9-((3-fluoro-1-hydroxy-2-propoxy)methyl)guanine; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil; C043457:fialuridine; D013937:Thymidine Kinase; D015774:Ganciclovir