Synthesis and evaluation of a fluorine-18 labeled antisense oligonucleotide as a potential PET tracer for iNOS mRNA expression.
Inducible NO synthase (iNOS) is overexpressed in inflammatory bowel diseases. An antisense oligonucleotide with good hybridization properties for iNOS mRNA was selected using RT-PCR. The oligonucleotide was reliably labeled with fluorine-18 using N-(4-[(18)F]fluorobenzyl)-2-bromoacetamide. Cellular uptake and efflux of oligonucleotide complexed with FuGENE-6 were rapid, unlike naked oligonucleotide, which hardly accumulated. However, neither uptake nor efflux showed any selectivity for iNOS expressing cells. The oligonucleotide showed a high level of non-specific binding, which may have obscured its specific hybridization to iNOS mRNA.
de Vries
Erik F J
EF
PET Center, Groningen University Hospital, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. e.f.j.de.vries@pet.azg.nl
Vroegh
Joke
J
Dijkstra
Gerard
G
Moshage
Han
H
Elsinga
Philip H
PH
Jansen
Peter L M
PL
Vaalburg
Willem
W
D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D005240:Feasibility Studies; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics
D005462:Fluorine Radioisotopes; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II