Antilymphoma mouse
monoclonal antibody (MoAb) Lym-1, labeled with 67Cu or 131I, has demonstrated promising results in
radioimmunotherapy (RIT) for
lymphoma. Although 131I has played a central role in RIT thus far, some properties of 67Cu are preferable. A subset of our patients received both 67Cu- and 131I-labeled Lym-1, allowing a comparative evaluation of the two
radiopharmaceuticals administered to a matched population of patients. Four patients with B-lymphocytic
non-Hodgkin's lymphoma that had progressed despite standard
therapy entered trials of 67Cu- and 131I-labeled Lym-1, which were injected 3-26 days apart. Lym-1 was conjugated to 6-[p-(bromoacetamido)benzyl]-1,4,7,11-tetraazacyclotetradecane-N,N ',N",N'"-tetraacetic
acid (BAT) via
2-iminothiolane (2IT) and radiolabeled with 67Cu to prepare 67Cu-2IT-BAT-Lym-1; 131I-Lym-1 was preparred by the
chloramine-T reaction. Planar imaging was used to quantitate
67Cu-2IT-BAT-Lym-1 or 131I-Lym-1 in organs and
tumors daily for 3 days or longer.
67Cu-2IT-BAT-Lym-1 exhibited higher peak concentration in 92% (12 of 13) of
tumors and a longer
biological half-time in every
tumor than 131I-Lym-1. The mean
tumor concentration (%ID/g) of
67Cu-2IT-BAT-Lym-1 was 1.7, 2.2, and 2.8 times that of 131I-Lym-1 at 0, 24, and 48 h after injection, respectively. The mean
biological half-times of
67Cu-2IT-BAT-Lym-1 and 131I-Lym-1 in
tumor were 8.8 and 2.3 days, respectively. Consequently, the mean
tumor radiation dose delivered by
67Cu-2IT-BAT-Lym-1 was twice that of 131I-Lym-1, 2.8 (range 0.8-6.7), and 1.4 (range 0.4-35) Gy/GBq, respectively.
67Cu-2IT-BAT-Lym-1 delivered a lower marrow radiation dose than 131I-Lym-1; hence, the
tumor:marrow therapeutic indices were 29 and 9.7, respectively. Radiation doses from
67Cu-2IT-BAT-Lym-1 and 131I-Lym-1 to normal tissues were similar except for liver, which received a higher dose from
67Cu-2IT-BAT-Lym-1. Images obtained with
67Cu-2IT-BAT-Lym-1 were superior. Radiation dosimetry data for
67Cu-2IT-BAT-Lym-1 and 131I-Lym-1 agreed with corresponding data from the larger populations of patients from which the matched population for the current study was drawn. In conclusion,
67Cu-2IT-BAT-Lym-1 given to
non-Hodgkin's lymphoma patients in close temporal proximity to 131I-Lym-1 exhibited greater uptake and longer retention in
tumor, resulting in higher radiation dose and therapeutic index than 131I-Lym-1. These as well as other factors suggest that
67Cu-2IT-BAT-Lym-1 may be superior to 131I-Lym-1 for RIT.