Beatty B G, Kuhn J A, Hui T E, Fisher D R, Williams L E, Beatty J D
Division of General and Oncologic Surgery, City of Hope National Medical Centre, Duarte, California.
Cancer. 1994 Feb 1;73(3 Suppl):958-65. doi: 10.1002/1097-0142(19940201)73:3+<958::aid-cncr2820731331>3.0.co;2-e.
Radioimmunotherapy of nude mice bearing human tumor xenografts using 90Y-labeled monoclonal antibodies has resulted in slower tumor growth, decreased tumor burden, and increased survival times. Dosimetry estimates in the murine model usually were based on biodistribution data and standard Medical Internal Radiation Dose approaches. A new dosimetric model for the mouse that takes into consideration the small dimensions, mass, and proximity of murine organs has been developed based on self-organ absorbed and cross-organ doses.
Nude mice bearing carcinoembryonic antigen-expressing WiDr human colon cancer xenografts were injected with 240 microCi 90Y-anti-carcinoembryonic-antigen monoclonal antibodies and then killed at 12, 24, 72, 120, and 168 hours. Tumors and major organs were removed, weighed, and counted on a gamma counter. Using the resulting biodistribution data, the radiation doses to tumor and normal organs were calculated using the new dosimetric model for the mouse.
Three organs (the liver, kidneys, and large bowel) directly received > 50% of the total absorbed beta dose from radioactivity. Lungs, stomach, and marrow received the highest percentage (70-75%) of the total absorbed dose from adjacent organs. Tumor absorbed dose, estimated with the new dosimetric model, was three times less than that obtained with a MIRD-style calculation without correction for self-absorbed and cross-organ doses.
The new dosimetric model, which accounts more accurately for self-organ absorbed and cross-organ beta dose fraction, allows the calculation of tumor and organ doses in the murine model. Accurate estimation of radiation doses to tumor and critical organs, such as the marrow, spleen and kidneys, is important in determining the efficacy and toxicity of radioimmunotherapy regimens in animals and in subsequent human applications.
使用90Y标记的单克隆抗体对携带人肿瘤异种移植的裸鼠进行放射免疫治疗已导致肿瘤生长减缓、肿瘤负荷降低和存活时间延长。小鼠模型中的剂量测定估计通常基于生物分布数据和标准的医学内照射剂量方法。基于自吸收和跨器官剂量，已开发出一种考虑到小鼠器官尺寸小、质量轻和相邻关系的新的小鼠剂量测定模型。
给携带表达癌胚抗原的WiDr人结肠癌异种移植的裸鼠注射240微居里的90Y抗癌胚抗原单克隆抗体，然后在12、24、72、120和168小时处死。取出肿瘤和主要器官，称重，并在γ计数器上计数。利用所得的生物分布数据，使用新的小鼠剂量测定模型计算肿瘤和正常器官的辐射剂量。
三个器官（肝脏、肾脏和大肠）直接接受了来自放射性的总吸收β剂量的>50%。肺、胃和骨髓接受了来自相邻器官的总吸收剂量的最高百分比（70-75%）。用新的剂量测定模型估计的肿瘤吸收剂量比未校正自吸收和跨器官剂量的MIRD式计算所得的剂量低三倍。
新的剂量测定模型更准确地考虑了自吸收和跨器官β剂量分数，能够计算小鼠模型中的肿瘤和器官剂量。准确估计肿瘤和关键器官（如骨髓、脾脏和肾脏）的辐射剂量对于确定动物放射免疫治疗方案的疗效和毒性以及随后在人体中的应用非常重要。
