Clinical experience with rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: results of phase I trials.
Clinical experience with rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: results of phase I trials.
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用于放射免疫治疗的铼 186 标记单克隆抗体的临床经验：I 期试验结果。
DOI：
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发表时间：
1992
影响因子：
9.3
通讯作者：
D. C. Foisie
中科院分区：
文献类型：
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作者：
H. Breitz;P. Weiden;J. Vanderheyden;J. W. Appelbaum;M. Bjorn;M. Fer;S. B. Wolf;B. Ratliff;C. Seiler;D. C. Foisie
Re是一种具有物理和化学性质的放射性核素，适用于放射免疫治疗。使用186Re标记的鼠单抗进行了两个I期试验。难治性转移性上皮癌患者接受单剂量186Re标记的完整的肿瘤抗体NR-LU-10，25-120mCI/m2(n=15)或186Re标记的抗CEA变异抗体NR-CO-02的F(ab‘)2片段，25-200mCI/m2(n=31)。放射免疫治疗前，用99mTc标记的NR-LU-10Fab或99mTc标记的NR-CO-02F(ab‘)2显像确定抗体的肿瘤定位。在严重预治疗的患者中，186Re-NR-LU-10完整抗体和NR-CO-02 F(ab‘)2片段的剂量限制性骨髓抑制分别为120mCI/m2和150mCI/m2。在先前接受最小剂量治疗的患者中，NR-CO-02 F(ab‘)2的最大耐受量未达到200mci/m2。非骨髓毒性最小。接受完整NR-LU-10的所有患者和接受F(ab‘)2 NR-CO-02的患者中有86%的患者产生了人类抗鼠抗体。1例患者经186Re NR-CO-02治疗后部分缓解。我们的结论是，186Re标记的抗体可以安全地给药，显著的毒性仅限于骨髓。
Rhenium is a radionuclide with physical and chemical properties suitable for radioimmunotherapy. Two Phase I trials were carried out using 186Re-labeled murine monoclonal antibodies. Patients with refractory metastatic epithelial carcinoma received single doses of either 186Re-labeled intact NR-LU-10, a pancarcinoma antibody, 25-120 mCi/m2 (n = 15) or 186Re-labeled F(ab')2 fragment of NR-CO-02, an anti-CEA variant antibody, 25-200 mCi/m2 (n = 31). Prior to radioimmunotherapy, tumor localization of antibody was confirmed by 99mTc-labeled NR-LU-10 Fab or 99mTc-labeled NR-CO-02 F(ab')2 imaging. Dose-limiting myelosuppression was observed at 120 mCi/m2 following 186Re-NR-LU-10 intact antibody and at 150 mCi/m2 following NR-CO-02 F(ab')2 fragment in heavily pretreated patients. In patients with minimal prior therapy, a maximum tolerated dose for NR-CO-02 F(ab')2 was not reached by 200 mCi/m2. Non-marrow toxicity was minimal. Human anti-mouse antibody developed in all patients receiving intact NR-LU-10, and in 86% patients receiving F(ab')2 NR-CO-02. One patient treated with 186Re NR-CO-02 achieved a partial response. We conclude that 186Re-labeled antibody can be safely administered with significant toxicity limited to marrow.