title: An 86Y-labeled mirror-image oligonucleotide: influence of Y-DOTA isomers on the biodistribution in rats.
abstract: A mirror-image oligonucleotide (L-RNA) was radiolabeled with the positron emitting radionuclide (86)Y (t(1/2) = 14.7 h) via the bifunctional chelator approach. DOTA-modification of the L-RNA (sequence: 5'-aminohexyl UGA CUG ACU GAC-3'; MW 3975) was performed using (S)-p-SCN-Bn-DOTA. (86)Y radiolabeling of the DOTA-L-RNA produced more than one species as evidenced by HPLC radiometric detection. For the identification of the (86)Y-labeled L-RNA, the structural analogue nonradioactive precursor [Y((S)-p-NH2-Bn-DOTA)](-) was synthesized. Two coordination isomers were separated via HPLC adopting the square antiprismatic (SAP) and the twisted square antiprismatic (TSAP) geometry, respectively. Their stereochemical configuration in the solution state was assessed by NMR and circular dichroism spectroscopy. Both [Y((S)-p-NH2-Bn-DOTA)](-) isomers were converted into isothiocyanate derivatives [Y((S)-p-SCN-Bn-DOTA)](-) and conjugated to the L-RNA. The identity of the [(86)Y-DOTA]-L-RNA species was finally established by comparison of the radiometric ((86)Y) and UV-visible chromatographic profiles. Biodistribution studies in Wistar rats showed minor changes in the biodistribution profile of the [(86)Y((S)-p-NH2-Bn-DOTA)](-) complex isomers, while no significant differences were observed for the [(86)Y-DOTA]-L-RNA isomers. High renal excretions were found for the [(86)Y((S)-p-NH 2-Bn-DOTA)](-) complex isomers as well as for the L-RNA isomers.
authors.affiliation: Institute of Radiopharmacy, Forschungszentrum Dresden-Rossendorf, Germany.
authors.forename: Joern
authors.initials: J
authors.lastname: Schlesinger
authors.forename: Inge
authors.initials: I
authors.lastname: Koezle
authors.forename: Ralf
authors.initials: R
authors.lastname: Bergmann
authors.forename: Sergio
authors.initials: S
authors.lastname: Tamburini
authors.forename: Cristina
authors.initials: C
authors.lastname: Bolzati
authors.forename: Francesco
authors.initials: F
authors.lastname: Tisato
authors.forename: Bernhard
authors.initials: B
authors.lastname: Noll
authors.forename: Sven
authors.initials: S
authors.lastname: Klussmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Vonhoff
authors.forename: Frank
authors.initials: F
authors.lastname: Wuest
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Pietzsch
authors.forename: Joerg
authors.initials: J
authors.lastname: Steinbach
mesh_terms: D000818:Animals; D001345:Autoradiography; D001554:Benzene / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009841:Oligonucleotides / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D012313:RNA / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes
chemical_list: D006571:Heterocyclic Compounds; D009841:Oligonucleotides; D009942:Organometallic Compounds; D015021:Yttrium Radioisotopes; C113625:yttrium(III)-1,4,7,10-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid; D012313:RNA; D001554:Benzene