Electrochemical separation and purification of no-carrier-added 177Lu for radiopharmaceutical preparation: Translation from bench to bed

The entry of no-carrier-added (NCA) 177Lu in the arena of clinical nuclear medicine has revolutionized the practice of targeted radionuclide tumor therapy. In this study, we report the development of an electrochemical separation and purification procedure to obtain NCA 177Lu in a clinically usable form. The overall yield of the process developed was > 70% and it was reproducible in multiple batches. The effective specific activity of NCA 177Lu was 3.32 ± 0.04 TBq/mg and the radioisotope was found suitable for formulation of therapeutically relevant doses of [177Lu]Lu-DOTA-TATE with >98% radiolabeling yield. As a proof of concept, [177Lu]Lu-DOTA-TATE synthesized using electrochemically purified NCA 177Lu was administered in patients with proven neuroendocrine tumor (NET) and satisfactory preliminary clinical outcome was obtained. The feasibility of recovery of enriched (in 176Yb) target in chemical form suitable for reuse in the production of a fresh batch of NCA 177Lu was demonstrated, which makes the process economically viable. Overall, this robust and efficient radiochemical separation and purification technology might aid towards introduction of new 177Lu-based radiopharmaceuticals for use in clinical context in the foreseeable future.