Radiolabelled Monoclonal Antibody Distribution in Human Tumor during Radioimmunotherapy (RIT)
To optimize the delivery efficacy in RIT, a regional tissue distribution model and pharmacokinetics of radiolabelled mAbs in region solid tumor tissue were developed to quantify the time-dependent radioactivities on the free (CIA(t)) and bound (CIAR(t)) antibodies, the total amount of radioactivity per gram of solid tumor tissue (CIT(t)) in tumor tissue, and radioactivity on free antibodies in plasma (CIA-b(t)), under various conditions. The criteria for the optimal delivery in RIT are to maximize the area under the curve (AUC) of CIT(t), AUC(CIT(t)), and minimize the ratio activity in tumor to activity in plasma AUC(CIT)/AUC(CIAb). Our results showed that: 1) The association and dissociation rate coefficients of antibodies to receptors have the same effects on optimal delivery under our clinical conditions of radioactive isotope half life ~8.5 days, clearance rate of antibody in plasma 17.35 ml/hr in human, and the tumor antigen concentration is 3.82×1015 antigens/ml; 2) The change from 10-8 M to 10-9 M in the equilibrium dissociation constant has the most improvement in optimal delivery. In contrast, further change from 10-9 M to 10-10 M has only insignificant improvement.
Yonggang Lv Bingmei M.Fu Li Yang Nai-Kong V.Cheung
Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Educatio Department of Biomedical Engineering, The City College of the City University of New York, New York, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, USA
国际会议
成都
英文
1-3
2010-06-18（万方平台首次上网日期，不代表论文的发表时间）