Collet B, Pellen P, Martin A, Moisan A, Bourel D, Toujas L
Centre Régional de Lutte contre le Cancer Pontchaillou, Rennes, France.
Cancer Immunol Immunother. 1988;26(3):237-42. doi: 10.1007/BF00199935.
The monoclonal antibody, 3A33, directed against Mac-1 antigen which is expressed essentially on macrophages and polymorphonuclear cells, was injected i.v. into mice, as part of an attempt to visualize inflammatory lesions and tumours by external scintigraphy. The monoclonal antibody, a rat IgG2a, was conjugated with a bifunctional chelating agent, diethylenetriaminepentaacetic acid at a 1:1 molecular ratio and complexed with 111-indium, a procedure which apparently did not alter its binding to peritoneal macrophages and provided relatively stable cell labelling. An unrelated rat IgG2a of unknown specificity radiolabelled in the same manner as 3A33 served as a control. The uptake of i.v. injected 3A33 by peritoneal macrophages was up to 50 times that of unrelated IgG2a. After i.v. inoculation, the antibody accumulated in the liver, spleen, lung, in foot-pad inflammatory reactions induced by injection of Freund's adjuvant and in experimentally grafted tumours. The 3A33: non-specific IgG2a uptake ratio in inflammatory lesions and tumours, however, was much lower than for peritoneal macrophages and was generally close to 2. This was sufficient to obtain scintigraphic images of inflammations and tumours. The images obtained after injection of 3A33 were clearly of better quality than those given by the non-specific immunoglobulin. They could be improved by subtraction of the vascular images obtained after injection of 99m-technetium serum albumin. The labelling of Mac-1-positive blood mononuclear cells by in vitro incubation with radioactive 3A33 was not intense enough to allow scintigraphic imaging after in vivo re-infusion but seemed more selective than the injection of whole antibody in detecting inflammatory reactions. These results seem interesting in view of the potential human application to the detection inflammatory lesions and the appreciation of tumour inflammatory components. Possible improvements in the technique are discussed.
单克隆抗体3A33可靶向作用于主要在巨噬细胞和多形核细胞上表达的Mac-1抗原，作为通过外部闪烁扫描法使炎症性病变和肿瘤可视化尝试的一部分，将其静脉注射到小鼠体内。该单克隆抗体为大鼠IgG2a，以1:1分子比例与双功能螯合剂二乙烯三胺五乙酸缀合，并与铟-111络合，这一过程显然未改变其与腹膜巨噬细胞的结合，并提供了相对稳定的细胞标记。一种特异性未知的无关大鼠IgG2a以与3A33相同的方式进行放射性标记作为对照。腹膜巨噬细胞对静脉注射的3A33的摄取量是无关IgG2a的50倍。静脉接种后，抗体在肝脏、脾脏、肺中蓄积，在注射弗氏佐剂诱导的足垫炎症反应以及实验性移植肿瘤中也有蓄积。然而，炎症性病变和肿瘤中3A33与非特异性IgG2a的摄取比率远低于腹膜巨噬细胞，通常接近2。这足以获得炎症和肿瘤的闪烁扫描图像。注射3A33后获得的图像质量明显优于非特异性免疫球蛋白所提供的图像。通过减去注射锝-99m血清白蛋白后获得的血管图像可使其得到改善。通过与放射性3A33进行体外孵育对Mac-1阳性血液单核细胞进行标记，强度不足以在体内再输注后进行闪烁扫描成像，但在检测炎症反应方面似乎比注射完整抗体更具选择性。鉴于在检测炎症性病变和评估肿瘤炎症成分方面的潜在人类应用，这些结果似乎很有趣。文中还讨论了该技术可能的改进方法。
