Preparation and evaluation of the rhenium-188-labelled anti-NCA antigen monoclonal antibody BW 250/183 for radioimmunotherapy of leukaemia.

Abstract

Anti-NCA antigen antibody BW 250/183 (Anti-Granulocyte) localizes more than 50% of injected antibody dose to the bone marrow. Therefore, this antibody is promising for adjuvant conditioning radioimmunotherapy of bone marrow before bone marrow transplantation. To examine its potential use for radioimmunotherapy, we developed an efficient and reproducible technical protocol for labelling anti-NCA antigen antibody BW 250/183 with generator-produced rhenium-188, aiming at both high radiochemical yield and high specific activity. (188)Re-labelled BW 250/183 antibody was used in 12 patients with advanced leukaemia. Labelling of BW 250/183 with (188)Re was accomplished by the direct radiolabelling method using tris-(2-carboxyethyl) phosphine (TCEP) as the reducing agent. Twelve patients with recurrent acute or chronic leukaemia were treated with activities of 6.5-12.4 GBq of (188)Re-labelled BW 250/183. Standard gamma camera scintigraphy was used to evaluate the biodistribution, and a region of interest analysis together with the MIRDOSE 3.1 software was applied to determine the radiation doses to relevant tissues. The (188)Re-BW 250/183 antibody was labelled in high radiochemical yield, with high radiochemical purity (94%+/-3%) and specific activity (5.55-7.4 GBq/mg) within 1 h. The preliminary biodistribution studies showed persistent uptake of (188)Re-BW 250/183 in bone marrow. The radiation absorbed doses (mGy/MBq) delivered to the total body, red marrow, liver, spleen and kidneys were 0.13+/-0.02, 1.45+/-0.71, 0.43+/-0.21, 1.32+/-0.99 and 0.71+/-0. 17, respectively. TCEP reduction enabled the direct, fast and effective labelling of the monoclonal antibody BW 250/183 with (188)Re. Preliminary clinical results suggest delivery of a significant radiation dose to bone marrow and thus the potential for adjuvant conditioning therapy before BMT.