会議発表用資料 30th Annual Congress of the European Association of Nuclear Medicine - EANM ポスター発表のため

Fujiwara, Kentaro  ,  K.Koyama  ,  H.Akiba  ,  H.Iwanari  ,  Higashi, Tatsuya  ,  K.tsumoto  ,  T.Hamakubo

2017-10-21
内容記述
[Aim] CDH17 is a membrane protein that contributes cell-cell adhesion. CDH17 might have potential as a target protein for PET imaging of gastric cancer with high sensitivity and high specificity, because CDH17 is expressed at high level in not only primary site of gastric cancer, but also metastatic lymph nodes. We previously reported a PET imaging study using 64Cu-labeled anti-CDH17 monoclonal antibody (IgG) against CDH17-positive gastric cancer xenografts. Although 64Cu-anti-CDH17 IgG showed high tumor uptake, relatively long retention of agent in blood was observed. In order to improve the blood clearance of agent, we developed an anti-CDH17 minibody which is small molecule of anti-CDH17 IgG. In this study, we performed the biodistribution study of anti-CDH17 minibody labeled with 111In and compared with that of anti-CDH17 IgG. [Materials and Methods] The specificity of anti-CDH17 minibody was evaluated by cell ELISA. We conjugated anti-CDH17 minibody and anti-CDH17 IgG with 1, 4, 7-triazacylononane, 1-glutaric acid-4, 7-acetic acid (NODAGA). Then, those were labeled with 111In. CDH17-positive AGS xenograft mice were injected 370 kBq of 111In-anti-CDH17 minibody or 370 kBq of 111In-anti-CDH17 IgG via tail vein. Mice were euthanized at at 3, 6 and 24 hours post injection (p.i.). Tumor and normal tissues were collected. The percentage of injected dose per gram of tissue (%ID/g) was calculated for each organ.[Results] Cell ELISA using AGS cell line demonstrated the specificity of anti-CDH17 minibody for CDH17 antigen. In addition, we confirmed that NODAGA conjugation and radiolabeling did not impair the affinity of anti-CDH17 minibody. In the biodistribution study, tumor uptake of 111In-anti-CDH17 minibody and 111In-anti-CDH17 IgG was 10.2% and 19.2%ID/g at 24 h p.i., respectively. Rapid blood clearance of 111In-anti-CDH17 minibody was confirmed (0.78%ID/g at 24 h p.i.) compared with 111In-anti-CDH17 IgG (11.6%ID/g at 24 h p.i.). Tumor-to-blood ratio of 111In-anti-CDH17 minibody and 111In-anti-CDH17 IgG was 13.0 and 1.7 at 24 h p.i., respectively. 111In-anti-CDH17 minibody showed relatively high uptake in the liver, spleen and kidney compared with 111In-anti-CDH17 IgG.[Conclusion] Anti-CDH17 minibody has a potential for a promising PET agent for CDH17-positive gastric cancer and might contribute to determine the management of gastric cancer such as indication for neoadjuvant chemotherapy.
30th Annual Congress of the European Association of Nuclear Medicine - EANM ポスター発表のため

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