Optimising conditions for radiolabelling of DOTA-peptides with 90Y, 111In and 177Lu at high specific activities

Abstract

DOTA-conjugated peptides, such as [DOTA0, Tyr3]octreotide (DOTATOC) and [DOTA0,Tyr3]octreo-tate (DOTA-tate), can be labelled with radionuclides such as 90Y, 111In and 177Lu. These radiolabelled somato-statin analogues are used for peptide receptor radionuclide therapy (PRRT). Radioligands for PRRT require high specific activities. However, although these radionuclides are produced without addition of carrier, contaminants are introduced during production and as decay products. In this study, parameters influencing the kinetics of labelling of DOTA-peptides were investigated and conditions were optimised to obtain the highest achievable specific activity. The effects of contaminants were systematically investigated, concentration dependently, in a test model mimicking conditions for labelling with minimal molar excess of DOTA-peptides over radionuclide. Kinetics of labelling of DOTA-peptides were optimal at pH 4-4.5; pH <4 strongly slowed down the kinetics. Above pH 5, reaction kinetics varied owing to the formation of radionuclide hydroxides. Labelling with 90Y and 177Lu was completed after 20 min at 80°C, while labelling with 111In was completed after 30 min at 100°C. The effects of contaminants were systematically categorised, e.g. Cd2+ is the target and decay product of 111In and it was found to be a strong competitor with 111In for incorporation in DOTA. In contrast, Zr4+ and Hf4+, decay products of 90Y and 177Lu, respectively, did not interfere with the incorporation of these radionuclides. The following conclusions are drawn: (a) DOTA-peptides can be radiolabelled at high specific activity; (b) reaction kinetics differ for each radionuclide; and (c) reactions can be hampered by contaminants, such as target material and decay products.