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


METHODS
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.


RESULTS
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.


CONCLUSIONS
The biodistribution and metabolic profiles of [18F]-L-DNA and [18F]-L-RNA Spiegelmers highlight their potential as radiotracers for in vivo imaging applications.
Boisgard
Raphaël
R
Laboratoire d'Imagerie de l'Expression des Gènes, CEA, Service Hospitalier Frédéric Joliot, INSERM ERM 103, Orsay, France.
Kuhnast
Bertrand
B
Vonhoff
Stefan
S
Younes
Chéraz
C
Hinnen
Françoise
F
Verbavatz
Jean-Marc
JM
Rousseau
Bernard
B
Fürste
Jens Peter
JP
Wlotzka
Britta
B
Dollé
Frédéric
F
Klussmann
Sven
S
Tavitian
Bertrand
B
D000818:Animals; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D009841:Oligonucleotides / Q000493:pharmacokinetics*; D009928:Organ Specificity; D010215:Papio; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes; D009841:Oligonucleotides; D019275:Radiopharmaceuticals