Dauer Lawrence T, Boylan Daniel C, Williamson Matthew J, St Germain Jean, Larson Steven M
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Health Phys. 2009 May;96(5):550-7. doi: 10.1097/01.HP.0000342831.26198.eb.
The monoclonal antibody (mAb) A33 detects a membrane antigen that is expressed on greater than 95% of metastatic human colorectal cancers. Previous studies have shown excellent tumor-targeting of (131)I-labeled murine and humanized forms of the mAb. A retrospective analysis of whole-body clearance in the murine form was performed for comparison to the humanized form. Serial whole-body dose rate measurements were obtained for 55 treatments on 30 patients participating in phase I/II dose escalation studies of therapeutic (131)I-murine A33 mAb. Whole-body retention fractions over time were derived. Each treatment was fit with exponential curves to determine the effective half-lives and corresponding clearance fractions. There was a large variability in the calculated mono-exponential clearance effective half-life time, with a mean value of 36.5 h +/- 8.5 h. A bi-exponential fit of all combined data shows that 60% of the administered dose rapidly clears with a biological half-time of 23.9 h and 40% clears with a slower biological half-time of 101.2 h. The whole-body clearance proved to be more rapid in the murine form when compared with recent studies on the humanized form of radiolabeled A33 mAb. The variability in whole-body clearance reinforces the need for patient-specific tracer dosimetry for clinical care and radiation safety precautions. In addition, the slower clearance of the humanized form of the A33 mAb requires longer term radiation safety precautions than the earlier murine form. As other monoclonal antibodies progress from murine to humanized forms, radiopharmacokinetics should be evaluated for clinical and radiation safety implications.
单克隆抗体（mAb）A33可检测一种膜抗原，该抗原在超过95%的转移性人类结直肠癌中表达。先前的研究表明，（131）I标记的鼠源和人源化形式的单克隆抗体具有出色的肿瘤靶向性。对鼠源形式的全身清除进行了回顾性分析，以与人性化形式进行比较。对参与治疗性（131）I - 鼠源A33单克隆抗体I/II期剂量递增研究的30名患者的55次治疗进行了连续全身剂量率测量。得出了随时间变化的全身滞留分数。对每次治疗进行指数曲线拟合，以确定有效半衰期和相应的清除分数。计算出的单指数清除有效半衰期时间存在很大差异，平均值为36.5小时±8.5小时。对所有合并数据进行双指数拟合表明，60%的给药剂量以23.9小时的生物半衰期快速清除，40%以101.2小时的较慢生物半衰期清除。与最近关于放射性标记A33单克隆抗体人源化形式的研究相比，鼠源形式的全身清除更快。全身清除的变异性强化了在临床护理和辐射安全预防措施中进行患者特异性示踪剂剂量测定的必要性。此外，A33单克隆抗体人源化形式的清除较慢，需要比早期鼠源形式更长时间的辐射安全预防措施。随着其他单克隆抗体从鼠源形式发展到人源化形式，应评估放射性药物动力学对临床和辐射安全的影响。
