TY - JOUR
T1 - Are Radiometal-Labeled Antibodies Better Than Iodine-131-Labeled Antibodies
T2 - Comparative Pharmacokinetics and Dosimetry of Copper-67-, Iodine-131-, and Yttrium-90-Labeled Lym-1 Antibody in Patients with Non-Hodgkin's Lymphoma
AU - Denardo, Gerald L
AU - DeNardo, Sally J.
AU - O'Donnell, Robert T
AU - Kroger, Linda A.
AU - Kukis, David L.
AU - Meares, Claude F.
AU - Goldstein, Desiree S.
AU - Shen, Sui
PY - 2000/9
Y1 - 2000/9
N2 - 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 131 I-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-BAD-Lym-1 for non-Hodgkin's lymphoma radioimmunotherapy.
AB - 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 131 I-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-BAD-Lym-1 for non-Hodgkin's lymphoma radioimmunotherapy.
KW - Copper-67
KW - Iodine-131
KW - Radiation dosimetry
KW - Radioimmunotherapy
KW - Yttrium-90
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M3 - Article
C2 - 11707820
AN - SCOPUS:0034280393
VL - 1
SP - 118
EP - 126
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
SN - 2152-2669
IS - 2
ER -