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

采用荷人肿瘤裸鼠模型，研究了几种药物对放射性标记单克隆抗体的药代动力学和生物分布的影响。结果表明：（1）由胶原蛋白和天然干扰素-α组成的干扰素-微条可使血中干扰素水平保持稳定5天。肿瘤细胞对CEA单克隆抗体的摄取也比对照组增加一倍。它增加了In-111从血液中的清除，从而使Y-99 m标记抗体的剂量学有利于放射免疫治疗。（2）低剂量IL-2不仅能增加肿瘤组织对~（99）Tc标记抗体的摄取，而且能增加正常组织对~（99）Tc标记抗体的摄取。IL-2可以与抗体结合而不丧失其增加血管通透性的作用。放射性标记抗体与IL-2偶联的生物分布研究目前正在进行中。（3）维拉帕米、利多卡因、莫能菌素、氯喹均可使~（125）I标记抗体的肿瘤滞留时间延长。这些实验结果表明，所研究的药物增强了碘标记抗体对肿瘤的靶向作用。

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.