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 Y-86(III) and Ga-68(III) in radiochemical yields of 76% and 93%, respectively. Compound 4a represents the first example of an oligonucleotide labelled with the positron emitter Y-86. Biodistribution studies of the Y-86-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 Y-86-DOTA chelate in vivo.