In Vivo Imaging and Pharmacokinetics of Oligonucleotides
1999
Abstract Important efforts have been done in the last ten years to evaluate oligonucleotides (ONs) as potential therapeutic agents. Despite the simplicity of drug design due to the Watson-Crick rules, ONs are poor drug candidates because of their lack of stability, cell penetration and bioavailability. To circumvent these disadvantages, numerous chemical modifications have been proposed, but their evaluation in animals is painstaking. We present here a set of methods allowing to follow in vivo the pharmacokinetics and biodistribution of fluorine-18 oligonucleotides, injected in living primates, with Positron Emission Tomography (PET). The radioactivity associated with an ON in three different chemistries allowed us to image quantitatively and describe the whole body pharmacokinetics. Together with metabolic analysis of plasmatic samples this method provide a full description of any ON.
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