Biodistribution of iodine-125 labeled monoclonal antibody/interleukin-2 immunoconjugate in athymic mice bearing human tumor xenografts.
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.
Nakamura
K
K
Department of Radiology, Keio University School of Medicine, Tokyo, Japan.
Kubo
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics*; D007376:Interleukin-2 / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000532:radiotherapy*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007376:Interleukin-2; D007457:Iodine Radioisotopes