Are Radiometal-Labeled Antibodies Better Than Iodine-131–Labeled Antibodies: Comparative Pharmacokinetics and Dosimetry of Copper-67–, Iodine-131–, and Yttrium-90–Labeled Lym-1 Antibody in Patients with Non-Hodgkin's Lymphoma

Abstract

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 (67Cu), iodine-131 (131I), or yttrium-90 (90Y), has been effective salvage therapy for patients with non-Hodgkin's lymphoma. Although 131I 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 67Cu-2IT-BAT-Lym-1, 131I-Lym-1, or 111In-2IT-BAD-Lym-1. Because 90Y does not have good emissions for imaging, indium-111 (111In), its analogue, was used as a surrogate to estimate 90Y-2IT-BAD-Lym- 1 pharmacokinetics and radiation dosimetry. Subsets of four patients in each group received 67Cu- and 131I-labeled Lym-1 or 111In- and 131I-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. 67Cu-2IT-BAT-Lym-1 and 90Y-2IT-BAD-Lym-1 exhibited higher cumulated activity concentrations and radiation absorbed doses per unit of administered radioactivity for tumors than did 131I-Lym-1. The mean tumor cumulated activity (area under the time-activity curve) concentrations per unit of administered radioactivity for 67Cu-2IT-BAT-Lym-1, 131I-Lym-1, and 90Y-2IT-BAD-Lym-1 were 96.89, 33.96, and 43.42 GBq-s/GBq/g, respectively. The mean tumor radiation doses from 67Cu-2IT-BAT-Lym-1, 131I-Lym-1, and 90Y-2IT-BAD-Lym-1 were 2.5, 1.0, and 6.6 Gy/GBq, respectively, because 90Y deposits more radiation per unit of administered radioactivity. Per unit of administered radioactivity, radiation doses from 67Cu-2IT-BAT-Lym-1 and 131I-Lym-1 to normal tissues were similar except that the liver received a higher dose from 67Cu-2IT-BAT-Lym-1 than from 131I-Lym-1; radiation doses to normal tissues from 90Y-2IT-BAD-Lym-1 were generally higher. Consequently, the therapeutic indices (ratio of radiation doses to tumor and normal tissues) for 67Cu-2IT-BAT-Lym-1, and less generally for 90Y- 2IT-BAD-Lym-1, were more favorable when compared to those for 131I-Lym-1. Data from the matched subsets of patients showed similar therapeutic indices to those for the groups of patients. 67Cu-2IT-BAT-Lym-1 showed more potential than 131I-Lym-1 or 90Y-2IT-BADLym- 1 for non-Hodgkin's lymphoma radioimmunotherapy