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.