Mariani G, Molen N, Bacciardi D, Boggi U, Bonino C, Costa A, Viacava P, Castagna M, Bodei L, Tarditi L
CNR Institute of Clinical Physiology, University of Pisa, Italy.
J Nucl Biol Med (1991). 1994 Dec;38(4 Suppl 1):145-50.
This pharmacokinetic study was performed in order to assess the potential usefulness of the murine monoclonal antibody (MoAb) AR-3-IgG1 as an immunoscintigraphy agent for pancreatic cancer. This MoAb, which defines a mucin-like antigen (CAR-3) expressed by a large fraction of pancreatic cancers, shows in fact favourable in vivo localizing properties in the experimental animal model of human tumor xenograft. 131I-AR-3-IgG1 was injected i.v. into 5 patients with suspected pancreatic cancer. Whole-body maps and spot views of the abdominal area were recorded with a computerized gamma-camera, and specific regions of interest drawn over the liver and spleen helped to define the kinetics of activity in these organs. Blood samples taken from 0.1-144 hours post-injection and daily urine collections over the same interval served to define the kinetics of plama distribution and removal of activity from the body. Different multicompartmental models were tested to fit the experimental data, assuming as the starting hypothesis that there was to be significant nonspecific tracer accumulation in the liver, spleen and bone marrow, as already observed for the majority of radioiodinated murine MoAbs injected into humans. Surgery confirmed pancreatic cancer in 3 out of the 5 patients (chronic pancreatitis and periampullary cancer in one each); in all these 3 patients immunostaining with the MoAb AR-3 demonstrated the presence of the CAR-3 antigen (with a cytoplasmic and endoluminal/secretory pattern of distribution). Nonspecific radioactivity accumulation in the liver, spleen and bone marrow was extremely low, linked essentially to the blood pool effect of circulating activity in these organs.(ABSTRACT TRUNCATED AT 250 WORDS)
进行这项药代动力学研究是为了评估鼠单克隆抗体（MoAb）AR-3-IgG1作为胰腺癌免疫闪烁显像剂的潜在效用。该单克隆抗体可识别大部分胰腺癌所表达的一种黏蛋白样抗原（CAR-3），实际上在人肿瘤异种移植实验动物模型中显示出良好的体内定位特性。将131I-AR-3-IgG1静脉注射到5例疑似胰腺癌患者体内。用计算机伽马相机记录全身图像和腹部区域的局部图像，在肝脏和脾脏上绘制特定的感兴趣区域，有助于确定这些器官中活性的动力学变化。在注射后0.1至144小时采集血样，并在同一时间段内每日收集尿液，以确定血浆分布动力学和体内活性清除情况。测试了不同的多室模型以拟合实验数据，起始假设是肝脏、脾脏和骨髓中会有明显的非特异性示踪剂蓄积，正如大多数注入人体的放射性碘化鼠单克隆抗体所观察到的那样。手术证实5例患者中有3例患有胰腺癌（另外1例为慢性胰腺炎，1例为壶腹周围癌）；在所有这3例患者中，用单克隆抗体AR-3进行免疫染色显示存在CAR-3抗原（呈细胞质和腔内/分泌型分布模式）。肝脏、脾脏和骨髓中的非特异性放射性蓄积极低，基本上与这些器官中循环活性的血池效应有关。（摘要截短于250字）
