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

Ann Nucl Med. 2020 Jan;34(1):13-23. doi: 10.1007/s12149-019-01408-y. Epub 2019 Oct 12.

Abstract

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.

Keywords: Cadherin-17; Gastric cancer; Lymph-node metastasis; Radiolabeled antibody; SPECT.

MeSH terms

  • Animals
  • Cadherins / immunology*
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoconjugates / chemistry*
  • Immunoconjugates / immunology*
  • Immunoconjugates / pharmacokinetics
  • Indium Radioisotopes / chemistry*
  • Isotope Labeling
  • Lymphatic Metastasis
  • Mice
  • Neoplasm Staging
  • Single Photon Emission Computed Tomography Computed Tomography / methods*
  • Stomach Neoplasms / diagnostic imaging*
  • Stomach Neoplasms / pathology*
  • Tissue Distribution

Substances

  • CDH17 protein, human
  • Cadherins
  • Immunoconjugates
  • Indium Radioisotopes
  • Indium-111