Höglund Johanna, Orlova Anna, Sundin Anders, Lundqvist Hans, Tolmachev Vladimir
Division of Radiology, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden.
Oncol Rep. 2006 Jul;16(1):159-63.
Investigations into the cellular processing of radiolabeled monoclonal antibodies (mAbs) for their further use in radioimmunodiagnosis and cancer therapy are needed in order to understand the fate of internalized and catabolized mAbs. The anti-colorectal cancer mAb, A33, was labelled with 76Br and 125I using the direct Chloramine-T method, or by labelling N-succinimidyl para-(tri-methylstannyl) benzoate and its further conjugation to the mAb. The cellular processing of the four conjugates was investigated in SW1222 cells in vitro. Uptake of mAb was rapid, peaking after 14-16 h. Intracellular degradation was slow and the early loss of radioactivity was due to dissociation of cell-surface bound mAb. The indirect labelling resulted in stronger binding of the mAb as well as prolonged intracellular retention of the radiolabel. Direct and indirect halogen radiolabelling results in different cell-processing patterns of radiolabels, and radioactive catabolic products follow different routes of cellular excretion. The results of this cellular study indicate that indirect labelling is preferable to the direct Chloramine-T method.
为了了解内化和分解代谢的单克隆抗体（mAb）的命运，需要对放射性标记的单克隆抗体进行细胞处理方面的研究，以便其进一步用于放射免疫诊断和癌症治疗。使用直接氯胺-T法或通过标记对（三甲基锡基）苯甲酸N-琥珀酰亚胺酯并将其进一步与单克隆抗体偶联，用76Br和125I标记抗结直肠癌单克隆抗体A33。在体外对SW1222细胞中四种偶联物的细胞处理情况进行了研究。单克隆抗体的摄取迅速，在14-16小时后达到峰值。细胞内降解缓慢，放射性的早期损失是由于细胞表面结合的单克隆抗体解离所致。间接标记导致单克隆抗体的结合更强，以及放射性标记在细胞内的保留时间延长。直接和间接卤素放射性标记导致放射性标记的细胞处理模式不同，放射性分解代谢产物遵循不同的细胞排泄途径。这项细胞研究的结果表明，间接标记优于直接氯胺-T法。
