RadioimmunoPET: detection of colorectal carcinoma with positron-emitting copper-64-labeled monoclonal antibody.
RadioimmunoPET: detection of colorectal carcinoma with positron-emitting copper-64-labeled monoclonal antibody.
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发表时间：
1995-10
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通讯作者：
G. Philpott;S. Schwarz;C. Anderson;F. Dehdashti;J. Connett;K. Zinn;C. Meares;P. Cutler;M. Welch;B. Siegel
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作者：
G. Philpott;S. Schwarz;C. Anderson;F. Dehdashti;J. Connett;K. Zinn;C. Meares;P. Cutler;M. Welch;B. Siegel
将单克隆抗体的选择性肿瘤靶向特性与 PET 的卓越灵敏度和对比度分辨率相结合，可以改善肿瘤病灶的检测。方法 通过使用双功能螯合物（溴乙酰氨基苄基-TETA），用 64Cu（一种正电子发射放射性核素）标记抗结直肠癌单克隆抗体 (MAb 1A3)，并在 36 名疑似晚期原发性或转移性结直肠癌患者中进行评估。注射放射性药物（5-20 mg 蛋白质，10 mCi 64Cu）后，4 至 36 小时后进行 PET 一次或两次。所有患者均接受了 CT 扫描，18 名患者还接受了 [18F]氟脱氧葡萄糖 (FDG) PET 研究。结果 在 29 名患者中，证实有一个或多个肿瘤部位（n = 56），在 5 名患者中确认不存在活动性肿瘤，在其余 2 名患者中，肿瘤状态尚未确认。在 56 个已确认的肿瘤位点中，MAb-PET 检测到 40 个位点为活性增加的病灶（敏感性 71%）。 MAb-PET 的阳性预测值非常出色，范围从 89% (40/45) 到 96% (43/45)，具体取决于三个图像阳性但尚未确认的肿瘤部位的最终分类。此外，MAb-PET 检测到 11 个新的隐匿性肿瘤部位，包括 9 个直径小于 2.0 厘米的腹盆腔小病灶，而 CT 或 MRI 未检测到。没有出现并发症，但在注射后 1 至 12 个月进行测试的 29 名患者中，有 28% 的 HAMA 滴度显着升高。 5 至 20 mg MAb 1A3 没有明显的剂量相关效应。结论 这些 I/II 期结果表明，放射性标记单克隆抗体 PET（放射免疫 PET）可能在临床肿瘤学中具有重要应用，特别是用于检测腹部或骨盆中较小的结直肠肿瘤病灶以及确定准确的剂量测定。
UNLABELLED Detection of tumor foci may be improved by combining the selective tumor-targeting properties of a monoclonal antibody with the superior sensitivity and contrast resolution of PET. METHODS An anti-colorectal carcinoma monoclonal antibody (MAb 1A3) was labeled with 64Cu, a positron-emitting radionuclide, by use of a bifunctional chelate (bromoacetamidobenzyl-TETA) and evaluated in 36 patients with suspected advanced primary or metastatic colorectal cancer. After radiopharmaceutical injection (5-20 mg protein, 10 mCi 64Cu), PET was performed once or twice, 4 to 36 hr later. All patients had CT scans and 18 patients were also studied with [18F]fluorodeoxyglucose (FDG) PET. RESULTS In 29 patients, one or more tumor sites (n = 56) were proven, in 5 patients the absence of active tumor was confirmed and in the remaining 2, tumor status is not yet confirmed. Of the 56 confirmed tumor sites, 40 were detected by MAb-PET as foci of increased activity (sensitivity 71%). The positive predictive value of MAb-PET was excellent, ranging from 89% (40/45) to 96% (43/45), depending on the ultimate classification of three image-positive, but as yet unconfirmed tumor sites. Also, MAb-PET detected 11 new occult tumor sites, including 9 small abdominopelvic foci less than 2.0 cm in diameter that were not detected by CT or MRI. There were no complications, but significantly elevated HAMA titers were found in 28% of the 29 patients tested 1 to 12 mo after injection. There was no apparent dose-related effect from 5 to 20 mg MAb 1A3. CONCLUSION These Phase I/II results suggest that PET with radiolabeled MAbs (radioimmunoPET) may have important applications in clinical oncology, particularly for detecting smaller colorectal tumor foci in the abdomen or pelvis and for determining accurate dosimetry.