⁸⁶Y-labelled L RNA oligonucleotides as Molecular Probes for Positron Emission Tomography (PET)

A short 5’-aminohexyl-functionalised L RNA oligonucleotide 1 (sequence: UGA CUG ACU GAC 3’, MW 3975) was used to study the influence of two different ⁸⁶Y DOTA chelates on the biodistribution in Wistar rats. The L-oligonucleotide 1 was conjugated with 1,4,7,10 tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid (DOTA) using N-succinimide ester (DOTA-NHS) 2 and isothiocyanate derivative (p SCN bz DOTA) 4 to afford the corresponding amide 3 and thiourea 5, respectively. Both DOTA-functionalised L RNA oligonucleotides 3 and 5 were labelled with the medium half-life positron-emitting radiometal ⁸⁶Y (t_1/2 = 14.7 h) in 76 % and 85 % radiochemical yield. ⁸⁶Y-Complexes 3a and 5a represent the first examples of L-oligonucleotides labelled with the positron emitter ⁸⁶Y.
The in vivo biodistribution of ⁸⁶Y-complex 3a showed a faster elimination from the body via the kidneys compared to thiourea-containing ⁸⁶Y-complex 5a. Transient accumulation of radioactivity in the kidneys and the adrenals was found for both ⁸⁶Y-complexes 3a and 5a. After incubation of ⁸⁶Y-complex 5a in whole rat blood at 37°C no noticeable decomposition could be observed over 12 h as confirmed by HPLC-analysis