Mariani G, Molea N, Bacciardi D, Boggi U, Fornaciari G, Campani D, Salvadori P A, Giulianotti P C, Mosca F, Gold D V
Nuclear Medicine Service, DIMI, University of Genoa, Italy.
Cancer Res. 1995 Dec 1;55(23 Suppl):5911s-5915s.
This pharmacokinetic study was performed to assess the potential usefulness of the murine monoclonal antibody (MoAb) PAM4-IgG1 as an immunotargeting agent for pancreatic cancer imaging or therapy. This MoAb reacts specifically with mucin purified from human pancreatic cancer. 131I-labeled PAM4-IgG1 was injected i.v. into five patients with suspected pancreatic cancer. Whole-body scans and spot views of the abdominal area were recorded with a computerized gamma camera, and specific regions of interest were drawn over the liver and spleen to define the kinetics of activity in these organs. Blood samples taken from 0.1-144 h after injection served to define the kinetics of plasma distribution and removal of activity from the body. Surgery confirmed pancreatic cancer in four of the five patients, whereas chronic pancreatitis was present in the fifth patient; in all four pancreatic cancer patients, immunostaining with the MoAb PAM4 demonstrated the presence of the specific antigen, with a cytoplasmic and endoluminal/secretory pattern of distribution. Nonspecific radioactivity accumulation in the liver, spleen, and bone marrow was low, linked essentially to the blood pool effect of circulating activity in these organs. The overall quality of scintigraphic maps recorded over the abdomen was quite satisfactory due to the low liver and spleen activity, with good scintigraphic demonstration of the pancreatic cancers (either primary or metastatic); the patient subsequently found to have pancreatitis failed to show PAM4 targeting. Except in one patient with widespread peritoneal metastases (in whom these tumor implants were detected scintigraphically already 24-48 hours after tracer injection), scintigraphic evidence of the tumor lesions was usually late, starting at about 72-96 h after tracer injection. The results obtained in this preliminary study indicate the potential usefulness of MoAb PAM4 for immunoscintigraphy in patients with either primary and/or recurrent pancreatic cancer while also suggesting that the use of the faster-clearing Fab fragments of this MoAb probably would result in improved immunoscintigraphic properties.
进行这项药代动力学研究，以评估鼠单克隆抗体（MoAb）PAM4-IgG1作为胰腺癌成像或治疗免疫靶向剂的潜在效用。该单克隆抗体与人胰腺癌纯化的粘蛋白特异性反应。将131I标记的PAM4-IgG1静脉注射到5例疑似胰腺癌患者体内。用计算机γ相机记录全身扫描和腹部区域的局部视图，并在肝脏和脾脏上绘制特定的感兴趣区域，以确定这些器官中活性的动力学。注射后0.1-144小时采集的血样用于确定血浆分布动力学和体内活性清除情况。手术证实5例患者中有4例患有胰腺癌，而第5例患者患有慢性胰腺炎；在所有4例胰腺癌患者中，用单克隆抗体PAM4进行免疫染色显示存在特异性抗原，呈细胞质和腔内/分泌型分布。肝脏、脾脏和骨髓中的非特异性放射性积累较低，主要与这些器官中循环活性的血池效应有关。由于肝脏和脾脏活性较低，腹部记录的闪烁图总体质量相当令人满意，胰腺癌（原发性或转移性）的闪烁图显示良好；随后被发现患有胰腺炎的患者未显示PAM4靶向。除1例有广泛腹膜转移的患者（在该患者中，示踪剂注射后24-48小时已通过闪烁图检测到这些肿瘤植入物）外，肿瘤病变的闪烁图证据通常较晚，始于示踪剂注射后约72-96小时。这项初步研究获得的结果表明，单克隆抗体PAM4在原发性和/或复发性胰腺癌患者的免疫闪烁成像中具有潜在效用，同时也表明使用该单克隆抗体清除更快的Fab片段可能会改善免疫闪烁成像特性。
