An 86Y-labeled mirror-image oligonucleotide: influence of Y-DOTA isomers on the biodistribution in rats.
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.
Schlesinger
Joern
J
Institute of Radiopharmacy, Forschungszentrum Dresden-Rossendorf, Germany.
Koezle
Inge
I
Bergmann
Ralf
R
Tamburini
Sergio
S
Bolzati
Cristina
C
Tisato
Francesco
F
Noll
Bernhard
B
Klussmann
Sven
S
Vonhoff
Stefan
S
Wuest
Frank
F
Pietzsch
Hans-Juergen
HJ
Steinbach
Joerg
J
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
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