Radioimmunotherapy using radiolabeled
monoclonal antibodies against
tumor-associated
antigens has been efficacious, particularly in the treatment of radiosensitive
malignancies such as
lymphoma. Antilymphoma
monoclonal antibody Lym-1, labeled with
copper-67 ((67)Cu),
iodine-131 ((131)I), or
yttrium-90 ((90)Y), has been effective
salvage therapy for patients with
non-Hodgkin's lymphoma. Although (131)I has had the dominant role in
radioimmunotherapy thus far, several properties of radiometals are preferable. A total of 70 patients with B-lymphocytic
non-Hodgkin's lymphoma were studied using (67)Cu-2IT-BAT-Lym-1, (131)I-Lym-1, or (111)In-2IT-BAD-Lym-1. Because (90)Y does not have good emissions for imaging,
indium-111 ((111)In), its analogue, was used as a surrogate to estimate (90)Y-2IT-BAD-Lym-1 pharmacokinetics and radiation dosimetry. Subsets of four patients in each group received (67)Cu- and (131)I-labeled Lym-1 or (111)In- and (131)I-labeled Lym-1, allowing direct comparisons of the
radioimmunoconjugates. Sequential blood samples and planar images were used to quantitate
radioimmunoconjugate in tissues in order to determine pharmacokinetics and radiation dosimetry. (67)Cu-2IT-BAT-Lym-1 and (90)Y-2IT-BAD-Lym-1 exhibited higher cumulated activity concentrations and radiation absorbed doses per unit of administered radioactivity for
tumors than did (131)I-Lym-1. The mean
tumor cumulated activity (area under the time-activity curve) concentrations per unit of administered radioactivity for (67)Cu-2IT-BAT-Lym-1, (131)I-Lym-1, and (90)Y-2IT-BAD-Lym-1 were 96.89, 33.96, and 43.42 GBq-s/GBq/g, respectively. The mean
tumor radiation doses from (67)Cu-2IT-BAT-Lym-1, (131)I-Lym-1, and (90)Y-2IT-BAD-Lym-1 were 2.5, 1.0, and 6.6 Gy/GBq, respectively, because (90)Y deposits more radiation per unit of administered radioactivity. Per unit of administered radioactivity, radiation doses from (67)Cu-2IT-BAT-Lym-1 and (131)I-Lym-1 to normal tissues were similar except that the liver received a higher dose from (67)Cu-2IT-BAT-Lym-1 than from (131)I-Lym-1; radiation doses to normal tissues from (90)Y-2IT-BAD-Lym-1 were generally higher. Consequently, the therapeutic indices (ratio of radiation doses to
tumor and normal tissues) for (67)Cu-2IT-BAT-Lym-1, and less generally for (90)Y-2IT-BAD-Lym-1, were more favorable when compared to those for (131)I-Lym-1. Data from the matched subsets of patients showed similar therapeutic indices to those for the groups of patients. (67)Cu-2IT-BAT-Lym-1 showed more potential than (131)I-Lym-1 or (90)Y-2IT-BAD-Lym-1 for
non-Hodgkin's lymphoma radioimmunotherapy.