Philpott G W, Siegel B A, Schwarz S W, Connett J M, Rocque P A, Fleshman J W, Wallis J W, Baumann M, Sun Y, Martell A E
Jewish Hospital of St. Louis, Department of Surgery, Missouri 63110.
Dis Colon Rectum. 1994 Aug;37(8):782-92. doi: 10.1007/BF02050143.
This study was designed to evaluate a new anticolorectal carcinoma monoclonal antibody (1A3), conjugated with the bifunctional chelating agent N,N'-bis(2-hydroxybenzyl)1(4-bromoacetamidobenzyl)1,2-ethylenediam ine-N,N'- diacetic acid and labeled with indium-111, in a Phase I/II study involving 38 patients with localized or advanced colorectal cancer.
Patients were injected with indium-111-N,N'-bis(2-hydroxybenzyl) 1(4-bromoacetamidobenzyl)1,2-ethylenediamine-N,N'-diacetic acid-monoclonal antibody 1A3 (1-50 mg, 1-5 mCi) and imaged at two or three sessions one to five days later. Scintigraphic findings were compared with radiologic, pathologic, surgical, and other clinical findings to assess the accuracy of radioimmunoscintigraphy.
At least one known tumor site was clearly defined by planar scintigraphy in 29 (76 percent) patients. Increased radioactivity was seen in 40 of 63 known tumor sites (37/43 abdominal-pelvic, 3/15 hepatic, and 0/5 pulmonary sites) without any apparent dose-related effects. Nineteen previously undetected sites were considered positive by imaging, and, of these, six were biopsy-proven tumor sites, four were probable tumor sites, three were definitely false positive sites, and six were probable false positive sites. Radioimmunoscintigraphy detected proven tumor in 15 of 16 patients with negative or equivocal computed tomography results. Of of the 28 patients with rectosigmoid cancer, 25 (89 percent) had positive studies with 34 of 47 tumor sites showing definite uptake on the scintigrams. This included 3 of 9 hepatic metastases. The only adverse reaction occurred in one patient who developed transient hives. Human anti-mouse antibody responses occurred in approximately one-half of the patients injected with doses of 10 or 50 mg.
This study shows that radioimmunoscintigraphy with this indium-111-labeled monoclonal antibody is safe, it can detect most nonhepatic abdominal-pelvic tumors with a positive predictive value of 83 (44/53) percent, and it should prove to be useful, particularly in the diagnosis of recurrent rectal carcinoma.
本研究旨在评估一种新的抗结肠直肠癌单克隆抗体（1A3），其与双功能螯合剂N，N'-双（2-羟基苄基）-1-（4-溴乙酰氨基苄基）-1,2-乙二胺-N，N'-二乙酸结合并标记铟-111，用于一项包含38例局部或晚期结肠直肠癌患者的I/II期研究。
给患者注射铟-111-N，N'-双（2-羟基苄基）-1-（4-溴乙酰氨基苄基）-1,2-乙二胺-N，N'-二乙酸-单克隆抗体1A3（1 - 50毫克，1 - 5毫居里），并在1至5天后进行两到三次成像。将闪烁扫描结果与放射学、病理学、手术及其他临床结果进行比较，以评估放射免疫闪烁成像的准确性。
平面闪烁扫描在29例（76%）患者中清晰界定了至少一个已知肿瘤部位。在63个已知肿瘤部位中的40个部位观察到放射性增加（43个腹盆腔部位中的37个，15个肝脏部位中的3个，5个肺部部位中的0个），且无明显剂量相关效应。19个先前未检测到的部位经成像判定为阳性，其中6个经活检证实为肿瘤部位，4个可能是肿瘤部位，3个肯定为假阳性部位，6个可能为假阳性部位。放射免疫闪烁成像在16例计算机断层扫描结果为阴性或不明确的患者中的15例中检测到已证实的肿瘤。在28例直肠乙状结肠癌患者中，25例（89%）检查呈阳性，47个肿瘤部位中的34个在闪烁扫描图上显示有明确摄取。这包括9个肝转移灶中的3个。唯一的不良反应发生在1例出现短暂性荨麻疹的患者身上。在注射10或50毫克剂量的患者中，约一半出现人抗鼠抗体反应。
本研究表明，使用这种铟-111标记的单克隆抗体进行放射免疫闪烁成像安全，它能检测出大多数非肝脏的腹盆腔肿瘤，阳性预测值为83（44/53）%，且应证明是有用的，特别是在复发性直肠癌的诊断中。
