Juweid M, Sharkey R M, Swayne L C, Griffiths G L, Dunn R, Goldenberg D M
Garden State Cancer Center, Belleville, New Jersey 07109, USA.
J Nucl Med. 1998 Jan;39(1):34-42.
The biodistribution, pharmacokinetics and dosimetry of 188Re-labeled MN-14, an IgG anti-carcinoembryonic antigen monoclonal antibody (MAb), were assessed in patients in advanced gastrointestinal cancer. In addition, the dose-limiting toxicity (DLT) and maximum tolerated dose of fractionated doses of this agent were determined.
Eleven patients were administered radioactive doses of directly labeled 188Re-MN-14 IgG, ranging from 20.5 mCi to 161.0 mCi (2.0 mg-4.9 mg). Ten of these patients received two or three MAb infusions, given 3-4 days apart, delivering total doses of 30 mCi/m2-80 mCi/m2. External scintigraphy was used to evaluate the MAb biodistribution, and quantitative external scintigraphic methods were used to determine the organ and tumor radiation doses.
The biodistribution studies showed enhanced 188Re-MN-14 uptake in the liver, spleen and kidneys, compared to that of 131I-MN-14. The biological T(1/2) values for 188Re-MN-14 in the blood and whole body (in hours) were 8.2 +/- 4.1 (n = 7) and 107.8 +/- 104.2 (n = 9), respectively (mean +/- s.d.). The radiation absorbed doses (cGy/mCi) delivered to the total body, red marrow, lungs, liver, spleen and kidneys were 0.5 +/- 0.05, 3.6 +/- 1.6, 2.0 +/- 0.8, 5.9 +/- 2.5, 7.1 +/- 1.9 and 8.5 +/- 2.8, respectively. Red marrow suppression was the only DLT observed. The maximum tolerated dose of fractionated doses of 188Re-MN-14 was estimated to be 60 mCi/m2.
Despite its relatively increased renal and hepatic uptake, red marrow suppression is the only DLT of 188Re-MN-14. The feasibility of administering relatively high doses of 188Re on a completely outpatient basis may make this agent a preferred candidate for radioimmunotherapy.
在晚期胃肠道癌患者中评估了188Re标记的MN-14（一种抗癌胚抗原IgG单克隆抗体（MAb））的生物分布、药代动力学和剂量学。此外，还确定了该药物分次给药的剂量限制毒性（DLT）和最大耐受剂量。
11例患者接受了直接标记的188Re-MN-14 IgG放射性剂量，范围为20.5 mCi至161.0 mCi（2.0 mg - 4.9 mg）。其中10例患者接受了两到三次MAb输注，间隔3 - 4天，总剂量为30 mCi/m2 - 80 mCi/m2。采用体外闪烁显像评估MAb的生物分布，并使用定量体外闪烁显像方法确定器官和肿瘤的辐射剂量。
生物分布研究显示，与131I-MN-14相比，188Re-MN-14在肝脏、脾脏和肾脏中的摄取增加。188Re-MN-14在血液和全身的生物半衰期（小时）分别为8.2±4.1（n = 7）和107.8±104.2（n = 9）（平均值±标准差）。全身、红骨髓、肺、肝、脾和肾脏的辐射吸收剂量（cGy/mCi）分别为0.5±0.05、3.6±1.6、2.0±0.8、5.9±2.5、7.1±1.9和8.5±2.
