In vivo biodistribution and pharmacokinetics of 18F-labelled Spiegelmers: a new class of oligonucleotidic radiopharmaceuticals.

Abstract

Single-stranded mirror-image oligonucleotides (Spiegelmers) are highly resistant to nuclease degradation and are capable of tightly and specifically binding to protein targets. Here we explored the potential of Spiegelmers as in vivo imaging probes for positron emission tomography (PET). We investigated the biodistribution and pharmacokinetics of [18F]-L-DNA and [18F]-L-RNA Spiegelmers by dynamic quantitative whole-body PET imaging after intravenous administration in non-human primates. Their metabolic profile was explored in primates and rats, and ex vivo autoradiography of [(125)I]-L-RNA was performed in rat kidneys, the major organ for Spiegelmer uptake. Both [18F]-L-DNA and [18F]-L-RNA Spiegelmers were metabolically stable in plasma during 2 h after injection. No evidence of non-specific binding was found with either type of Spiegelmer in any tissue. The biodistribution and metabolic profiles of [18F]-L-DNA and [18F]-L-RNA Spiegelmers highlight their potential as radiotracers for in vivo imaging applications.