Holmberg S B, Hafström L, Aronsson E F, Gretarsdottir J, Jacobsson L, Mattsson S, Lindholm L
Department of Surgery, University of Göteborg, Sahlgrenska Hospital, Sweden.
Acta Oncol. 1989;28(5):699-703. doi: 10.3109/02841868909092296.
This experimental study in rats examines the influence of tumour growth and RES function modulation on the kinetics of iodinated MAb IgG1 C241. The study was designed to investigate unspecific accumulation in liver and blood. C241 is raised against human colon adenocarcinoma COLO 205 and reacts with SiLea tumour-associated antigen, also known as tumour-associated antigen 19-9. In 26 rats, 2 micrograms 125I MAb C241 (lodobead labelling method) was given i.v. Blood, organ and tumour content was measured at 0.5, 24, 72 and 144 h. In 61 rats, 10 micrograms 131I MAb C241 (lodogen labelling method) was given i.v. The rats were divided into a non-tumour and a tumour-bearing group and subjected to RES function modulation with Zymosan stimulation or methyl palmitate depression. A syngeneic nitrosoguanidine-induced colonic carcinoma--mean 11 g--was growing in back subcutaneous tissue and hind leg musculature. Serum content of tumour-associated antigen was not found on IRMA testing and tumour content of SiLea ganglioside antigen was found only on lipid binding phase assay. The half-time in blood of iodinated MAb C241 was three days. In-vivo release of iodine was tested by plasma separation on a gel column. More than 90% of the iodine was in the IgG fraction. The activity distribution was almost in equilibrium after 24 h. A tumour/blood activity concentration ratio of 0.5 and liver/blood ratio of 0.3 remained at 72 h and 144 h. Radionuclide accumulation was equally low in the macrophage-rich liver and the kidneys. Tumour-bearing animals had significantly lower blood content (0.37 versus 0.99% g-1) and liver content (0.09 versus 0.31% g-1) at 144 h than non-tumour-bearing rats. The whole body content at 144 h was also lower (24% versus 35% of administered activity) (p = 0.10). Modulation of RES function had no significant influence on the whole body, blood or liver content of 131I MAb C241 activity in non-tumour-bearing animals. In tumour-bearing animals, RES stimulation with Zymosan increased the whole body, liver and blood content of 131I activity. The two tested methods of iodination gave similar results.
这项针对大鼠的实验研究考察了肿瘤生长和网状内皮系统（RES）功能调节对碘化单克隆抗体IgG1 C241动力学的影响。该研究旨在探究其在肝脏和血液中的非特异性蓄积情况。C241是针对人结肠腺癌COLO 205产生的，可与唾液酸化乳糖胺（SiLea）肿瘤相关抗原反应，该抗原也被称为肿瘤相关抗原19-9。给26只大鼠静脉注射2微克125I标记的单克隆抗体C241（碘珠标记法）。在0.5、24、72和144小时测量血液、器官和肿瘤中的含量。给61只大鼠静脉注射10微克131I标记的单克隆抗体C241（lodogen标记法）。将大鼠分为非肿瘤组和荷瘤组，通过酵母聚糖刺激或棕榈酸甲酯抑制对RES功能进行调节。一种同基因亚硝基胍诱导的结肠癌——平均重量为11克——生长在背部皮下组织和后腿肌肉组织中。免疫放射分析（IRMA）检测未发现肿瘤相关抗原的血清含量，仅在脂质结合相分析中发现了SiLea神经节苷脂抗原的肿瘤含量。碘化单克隆抗体C241在血液中的半衰期为三天。通过凝胶柱上的血浆分离测试碘的体内释放情况。超过90%的碘存在于IgG组分中。24小时后活性分布几乎达到平衡。在72小时和144小时时，肿瘤/血液活性浓度比为0.5，肝脏/血液活性浓度比为0.3。富含巨噬细胞的肝脏和肾脏中的放射性核素蓄积同样较低。在144小时时，荷瘤动物的血液含量（0.37%对0.99%克-1）和肝脏含量（0.09%对0.31%克-1）显著低于非荷瘤大鼠。144小时时的全身含量也较低（给药活性的24%对35%）（p = 0.10）。RES功能调节对非荷瘤动物体内131I标记的单克隆抗体C241活性的全身、血液或肝脏含量没有显著影响。在荷瘤动物中，用酵母聚糖刺激RES可增加131I活性的全身、肝脏和血液含量。两种测试碘化方法得到了相似的结果。
