Cu-67- versus I-131-labeled Lym-1 antibody: Comparative pharmacokinetics and dosimetry in patients with non-Hodgkin's lymphoma

Antilymphoma mouse monoclonal antibody (MoAb) Lym-1, labeled with Cu-67 or I-131, h, demonstrated promising results in radioimmunotherapy (RTT) for ly mphoma. Although I-131 has played a central role in RIT thus far, some prop erties of Cu-67 are preferable. A subset of our patients received both Cu-6 7- and I-131-labeled Lym-1, allowing a comparative evaluation of the two ra diopharmaceuticals administered to a matched population of patients. Four p atients with B-lymphocytic non-Hodgkin's lymphoma that had progressed despi te standard therapy entered trials of Cu-67- and I-131-labeled Lym-1, which were injected 3-26 days apart. Lym-1 was conjugated to 6-[p-(bromoacetamid o)benzyl]-1,4,7,11-tetraazacyclotetradecane-N,N,N ",N'''-tetraacetic acid ( BAT) via 2-iminothiolane (2IT) and radiolabeled with Cu-67 to prepare Cu-67 -2IT-BAT-Lym-1; I-131-Lym-1 was preparred by the chloramine-T reaction. Pla nar imaging was used to quantitate Cu-67-2IT-BAT-Lym-1 or I-131-Lym-1 in or gans and tumors daily for 3 days or longer. Cu-67-2IT-BAT-Lym-1 exhibited h igher peak concentration in 92% (12 of 13) of tumors and a longer biologica l half-time in every tumor than I-131-Lym-1. The mean tumor concentration ( %ID/g) of Cu-67-2IT-BAT-Lym-1 was 1.7, 2.2, and 2.8 times that of (131)Lym- 1 at 0, 24, and 48 h after injection, respectively. The mean biological hal f-times of Cu-67-2IT-BAT-Lym-1 and I-131-Lym-1 in tumor were 8.8 and 2.3 da ys, respectively. Consequently, the mean tumor radiation dose delivered by Cu-67-2IT-BAT-Lym-1 was twice that of I-131-Lym-1, 2.8 (range 0.8-6.7), and 1.3 (range 0.4-35) Gy/GBq, respectively. Cu-67-2IT-BAT-Lym-1 delivered a l ower marrow radiation dose than I-131-Lym-1; hence, the tumor:marrow therap eutic indices were 29 and 9.7, respectively. Radiation doses from Cu-67-2IT -BAT-Lym-1 and I-131-Lym-1 to normal tissues were similar except for liver, which received a higher dose from Cu-67-2IT-BAT-Lym-1. Images obtained wit h Cu-67-2IT-BAT-Lym-1 were superior. Radiation dosimetry data for Cu-67-2IT -BAT-Lym-1 and I-131-Lym-1 agreed with corresponding data from the larger p opulations of patients from which the matched population for the current st udy was drawn. In conclusion, Cu-67-2IT-BAT-Lym-1 given to non-Hodgkin's ly mphoma patients in close temporal proximity to I-131-Lym-1 exhibited greate r uptake and longer retention in tumor, resulting in higher radiation dose and therapeutic index than I-131-Lym-1. These as well as other factors sugg est that Cu-67-2IT-BAT-Lym-1 may be superior to I-131-Lym-1 for RIT.