Synthesis and Radiopharmacological Characterisation of ⁸⁶Y- and ⁶⁸Ga-Labelled L-RNA Oligonucleotides as Molecular Probes for Positron Emission Tomography (PET)

Functionalisation of an L-RNA oligonucleotide with 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) was performed using the N-succinimide ester 2. The DOTA-functionalised L-RNA oligonucleotide 3 was radiolabelled with the positron-emitting radiometals ⁸⁶Y(III) and ⁶⁸Ga(III) in radiochemical yields of 76 % and 93 %, respectively. Compound 4a represents the first example of an oligonucleotide labelled with the positron emitter ⁸⁶Y. Biodistribution studies of the ⁸⁶Y-radiolabelled L-RNA oligonucleotide 4a were performed in Wistar rats showing higher levels of radioactivity in the adrenal glands and kidneys. The low bone uptake (0.19 %ID/g after 60 min) is indicative of the high kinetic stability of the ⁸⁶Y-DOTA chelate in vivo.