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111In-labeled anti-cadherin17 antibody D2101 has potential as a noninvasive imaging probe for diagnosing gastric cancer and lymph-node metastasis

DOI:10.1007/s12149-019-01408-y 期刊:Annals of Nuclear Medicine 出版年份:2019 更新时间:2025-09-16 10:30:52
摘要: Objective Cadherin-17 (CDH17) is a transmembrane protein that mediates cell–cell adhesion and is frequently expressed in adenocarcinomas, including gastric cancer. CDH17 may be an effective diagnostic marker for the staging of gastric cancer. Here, we developed an 111In-labeled anti-CDH17 monoclonal antibody (Mab) as an imaging tracer and performed biodistribution and single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging studies using mice with CDH17-positive gastric cancer xenografts. CDH17 expression in gastric cancer specimens was also analyzed. Methods The cross-reactivity and affinity of our anti-CDH17 Mab D2101 was evaluated by surface plasmon resonance analysis and cell enzyme-linked immunosorbent assay, respectively. Biodistribution and SPECT/CT studies of 111In-labeled D2101 (111In-D2101) were performed. CDH17 expression in gastric cancer specimens was evaluated by immunohistochemistry. Results Surface plasmon resonance analysis revealed that D2101 specifically recognizes human CDH17, but not murine CDH17. The affinity of D2101 slightly decreased as a result of the radiolabeling procedures. The biodistribution study revealed high uptake of 111In-D2101 in tumors (maximum, 39.2 ± 9.5% ID/g at 96 h postinjection), but low uptake in normal organs, including the stomach. Temporal SPECT/CT imaging with 111In-D2101 visualized tumors with a high degree of tumor-to-nontumor contrast. Immunohistochemical analysis revealed that, compared with HER2, which is a potential marker of N-stage, CDH17 had a higher frequency of positivity in specimens of primary and metastatic gastric cancer. Conclusion Our 111In-anti-CDH17 Mab D2101 depicted CDH17-positive gastric cancer xenografts in vivo and has the potential to be an imaging probe for the diagnosis of primary lesions and lymph-node metastasis in gastric cancer.
作者: Kentaro Fujiwara,Atsushi B. Tsuji,Osamu Kusano-Arai,Kouhei Tsumoto,Toshimitsu Momose,Takao Hamakubo,Tatsuya Higashi,Hitomi Sudo,Aya Sugyo,Hiroki Akiba,Hiroko Iwanari
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Investigating the potential of 111In-labeled anti-CDH17 monoclonal antibody D2101 as a noninvasive imaging probe for diagnosing gastric cancer and lymph-node metastasis.

The 111In-anti-CDH17 Mab D2101 exhibited high levels of tumor uptake and low background levels in the biodistribution and SPECT/CT studies in a CDH17-positive gastric cancer mouse model. CDH17 is a promising diagnostic marker, and radiolabeled D2101 has the potential to provide useful information for the N-staging of gastric cancer.

The study has several limitations: the uptake in CDH17-positive organs such as intestine may interfere distinguishing metastasis in lymph nodes around the stomach; the antibody does not have cross-reactivity to murine CDH17, limiting the prediction of pharmacokinetics in humans; CDH17 expression analysis was performed with a small sample size; and a more sensitive imaging technique might be needed to detect very small LN metastases.

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