Pharmacokinetic Study of Targeting Tumors with Radio-and Drug-conjugated Monoclonal Antibody

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Using athymic mice bearing human tumor xenografts, the effects of several drugs on the pharmacokinetics and biodistribution of radiolabeled monoclonal antibody were investigated. The following results were obtained :(1)The administration of Interferon-minipellet which consisted of collagen and natural interferon-alpha could keep the blood interferon level constant for 5 days. It also enhanced the uptake of radiolabeled anti-CEA monoclonal antibody in tumors with twice comparing with control mice. It increased in the clearance of In-111 from blood, thus making the dosimetry of Y-99m-labeled antibody favorable for radioimmunotherapy.(2)The administration of IL-2 with low dose increased the uptake of Tc-99m-labeled antibody not in the tumor but also in some normal tissues. IL-2 could be conjugated with antibody without loss of its action which increases in the permeability of blood vessels. The biodistribution study of radiolabeled antibody conjugated with IL-2 is currently underway.(3)The administration of verapamil, lidocaine, monensin, or chloroquine could make tumor retention time of I-125-labeled antibody longer. They increased the blood clearance rate of I-125, thus increasing the tumor-to-blood ratio remarkably.These experimental results indicated that drugs investigated augment the efficacy of targeting of tumors with iodine-labeled antibody.