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Biodistribution of iodine‐125 labeled monoclonal antibody/Interleukin‐2 immunoconjugate in athymic mice bearing human tumor xenografts
Author(s) -
Nakamura Kayoko,
Kubo Atsushi
Publication year - 1997
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19971215)80:12+<2650::aid-cncr41>3.0.co;2-8
Subject(s) - immunoconjugate , biodistribution , medicine , monoclonal antibody , conjugate , vascular permeability , carcinoembryonic antigen , antibody , pathology , cancer research , immunology , chemistry , cancer , in vitro , biochemistry , mathematical analysis , mathematics
BACKGROUND Some vasoactive drugs have been studied in the hope of altering the vascular permeability and/or blood of tumors to enhance monoclonal antibody (MoAb) uptake. The pretreatment of interleukin‐2 (IL‐2), one of the vasoactive reagents, produced a generalized vascular permeability, but its function was not tumor specific. Conversely, MoAb/IL‐2 immunoconjugates were developed that selectively alter the vasopermeability of tumors. In the current study the authors evaluated whether radiolabeled anti‐carcinoembryonic antigen (CEA) MoAb, ZCE025/IL‐2 immunoconjugate, specifically can enhance delivery of iodine‐125 (I‐125) to tumor sites. METHODS ZCE025 was conjugated with IL‐2, and the conjugate then labeled with I‐125. Biodistribution studies were performed in athymic mice bearing CEA‐producing human tumor (MKN45) xenografts. Mice were injected with I‐125‐ZCE025/IL‐2 conjugate, and I‐125 activities in the organs, including blood and tumor, were investigated at 1, 3, and 5 days after injection. Vascular permeability of the organs, including tumors, also was studied by using I‐131 labeled mouse serum albumin in three groups. RESULTS I‐125 labeled ZCE025/IL‐2 conjugate destroyed its lymphokine‐activated killer cell (LAK) activation, but retained a minimum of 75% of the antibody binding reactivity. Biodistribution of I‐125‐ZCE025/IL‐2 conjugate showed increased uptake of I‐125 in tumor by a factor of 1.5, 4.2, and 4.1 compared with I‐125‐ZCE025 on Days 1, 3, and 5, respectively. In contrast, I‐125 distribution was not enhanced in any organs except the tumor. Vascular permeability studies demonstrated that the physiologic effect of IL‐2 was tumor specific in the mice that received the I‐125‐ZCE025/IL‐2 conjugate. CONCLUSIONS These studies indicate that the administration of radiolabeled MoAb/IL‐2 double conjugate may enhance the therapeutic potential of radiolabeled MoAb without any pretreatment with IL‐2 or repeated injection of MoAb. Cancer 1997; 80:2650‐5. © 1997 American Cancer Society.