Radioimmunoimaging with recombinant light chain of human monoclonal anti-lung cancer antibody HB4C in vivo study by using lung cancer xenografted mice

去糖基化人抗肺癌单克隆抗体dHB 4C 5已建立其特异性识别肺癌的体内研究。该dHB 4C 5用In-DTPA标记，In-DTPA是用于成像的适当试剂。虽然In-DTPA标记的dHB 4C 5在小鼠移植瘤中的蓄积量高于In标记的对照IgM，但在图像上也观察到肝、肾和脾中的显著摄取。In-DTPA与dHB 4C 5的IgM（M900，0000）的低亲和力被认为是临床应用的限制，因为在正常器官中的高摄取。然后，我们尝试将dHB_4C_5的重组轻链C_5-L链（C_5 λ链）用In-DTPA进行标记，结果发现，用螯合DTPA标记的C_5 λ链的免疫活性较原C_5 λ链有所降低，而且In-111 DTPA标记的C_5 λ链在正常组织中也有蓄积。另一方面，将临床上常用的物理半衰期为6小时的放射性锝（Tc-99 M）用于标记C5 λ链。给药后28小时的图像清晰地显示了Tc-99 m标记的C5 λ链在肿瘤中的积聚。~（99）Tc标记的重组轻链C5 λ有望成为肺癌的显像剂。

The deglycosylated human monoclonal anti-lung cancer antibody, dHB4C5, has been establoshed it's specific recognition of lung cancer in vivo study. This dHB4C5 was labelled with In-DTPA which is adequate agent for imaging. Though higher accumulation of In-DTPA labeled dHB4C5 in the implanted tumor of mice than that's of In labeled control IgM was recognized, the remarkable uptake in liver, kidney, and spleen was also observed on images. The low affinity of In-DTPA to IgM,M900,0000 of dHB4C5, was thought to be limited application for clinical use because of high uptake in normal organs. Then, we tried to make recombinant light chain of dHB4C5, C5-L chain (C5lambda chain), and label with In-DTPA.The immunoactivity of C5lambda chain, however, was decreased compared with original C5lambda chain by using chelate DTPA.Furthermore, C5lambda chain labeled with In-111 DTPA was also accumulated in normal organs. On the otherhand, radioactive techinetium (Tc-99M), 6 hours physical half life, which is mostly used clinicaly, was applied to label with C5lambda chain. The accumulation of Tc-99m labeled C5lambda chain in tumor was shown on images 28 hours after administration clearly. Tc-99m labeled recombinant light chain C5lambda will become a promising imaging agent of lung cancer.