Transfer of copper from a chelated 67Cu-antibody conjugate to ceruloplasmin in lymphoma patients

The Lym-1 monoclonal antibody was conjugated with the bifunctional chelating agent 6 [p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane N,N',N",N"'-tetraacetic acid (BAT), using 2IT as a linker, and radiolabeled with Cu-67 to make the radiopharmaceutical, Cu-67-2IT-BAT-Lym-1, Ten patients received a total of Is doses of Cu-67-2IT-BAT-Lym-1 as targeted, systemic radiotherapy. The beta phase of blood clearance, when corrected for Cu-67 decay, was positive or flat, a phenomenon not observed in similar patients treated with I-131-Lym-1. The flat beta phase of brood clearance suggested recycling of Cu-67 from Cu-67-2IT-BAT-Lym-1 to another plasma protein. Therefore, the amount of Cu-67 transferred from the radiopharmaceutical to CP, Alb, and TF was measured using affinity-purified polyclonal antibodies. The fraction of plasma Cu-67 precipitated by anti human CP increased daily; most blood radioactivity was Cu-67-CP after a median of 4 days (range 2-7 days). The transfer of Cu-67 to CP was observed in all patients and was consistent from dose to dose within the same patient. An average of 2.8 +/- 1.5% (range 0.8-7.8%) of the Cu-67 dose (%ID) was transferred to CP. The release rate of Cu-67-CP from the liver into the blood was 0.9 +/- 0.4 %ID/day for the first 3 days. The Cu-67-CP effective clearance half life was 3.7 +/- 0.7 days. Subtraction of the Cu-67-CP activity from the total blood radioactivity yielded a biphasic blood clearance similar to that obtained for patients given I-131-Lym-1. Cu-67-CP increased the AUC for whole blood by 24 +/- 10%. The %ID of Cu-67 recycled correlated with GGT, ALT, and alkaline phosphatase revels; r = 0.958 (p < 0.001), 0.857 (p < 0.01), and 0.822 (p < 0.01), respectively. Albumin levels correlated negatively with recycled copper (r = -0.745, p < 0.05). The data suggest that the liver metabolizes Cu-67-2IT-BAT-Lym-1 and recycles a small fraction of the Cu-67, transferring it to CP. NUCL MED BIOL 26;7:841-845, 1999. (C) 1999 Elsevier Science Inc. All rights reserved.