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

DOTA-conjugated peptides, such as [DOTA⁰,Tyr³]octreotide (DOTATOC) and [DOTA⁰,Tyr³]octreotate (DOTA-tate), can be labelled with radionuclides such as ⁹⁰Y, ¹¹¹In and ¹⁷⁷Lu. These radiolabelled somatostatin 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.