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

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 111 In-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 111 In-labeled D2101 ( 111 In-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 111 In-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 111 In-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 111 In-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.

CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin

“…Consistent with published studies, TMA data in the present study showed that 66% of gastric cancer samples express CDH17. The aberrant expression has resulted in the attempts to use CDH17 as a target for cancer imaging and therapy [ 22 , 39 , 40 ]. In the present study, we identified two nanobodies specifically bound to CDH17 and E8 nanobody was extensively explored for gastric cancer imaging and targeted therapy due to its relatively higher affinity (~ 70 nM).…”

A Unified Transcriptional, Pharmacogenomic, and Gene Dependency Approach to Decipher the Biology, Diagnostic Markers, and Therapeutic Targets Associated with Prostate Cancer Metastasis

“…Elevated expression of genes such as ABCC5 [50], LRFN1 [59], ELOVL6 [58], and HTR2B [61] have been associated with metastasis in other cancer types. Recently, PET-based detection and monitoring of metastasis cancer has utilized the following antibodies: 111 In-labeled anti-CDH17 (gastric cancer) [114], 177 Lu-labeled anti-CD55 (lung cancer) [115], and radio-labeled anti-ERBB2 (various labeling, including 89 Zr, 64 Cu, 111 In) (breast cancer) [116]. The gene FOLH1 (folate hydrolase 1) is of particular interest since it codes for the transmembrane metalloenzyme PSMA (prostate-specific membrane antigen).…”

Antibody-Targeted Imaging of Gastric Cancer

“…ImmunoPET and immunoSPECT have been used for the non-invasive imaging of gastric cancer in both preclinical and clinical studies. The first section of the review will discuss the use of immunoPET in GC targeting the antigens carcinoma-associated antigen (MG7) [ 14 ], programmed death-1 (PD-1) [ 16 ], cadherin-17 (CDH17) [ 15 ], human epidermal growth factor receptors 2 and 3 (HER2 [ 5 , 9 , 21 , 22 , 23 , 24 ] and HER3 [ 12 ]), hepatocyte growth factor (HGF [ 11 ]), and the mesenchymal-epithelial transition factor (MET) [ 10 ]. As shown in Table 1 , FDA-approved or newly developed antibodies targeting membrane antigens were radiolabeled with gallium-68 ( 68 Ga), technetium-99m ( 99m Tc), indium-111 ( 111 In), copper-64 ( 64 Cu), zirconium-89 ( 89 Zr), and bromine-76 ( 76 Br) and used for PET or SPECT imaging of gastric tumors.…”

“…In a healthy adult, the gene that codes for the CDH17 protein is silenced; however, it is often expressed in gastric cancer, as well as other adenocarcinomas. In a recent study, the potential of CDH17 as a biomarker in GC was investigated through imaging techniques [ 15 ]. The anti-CDH17 monoclonal antibody D2101 was radiolabeled with indium-111 and administered to mice with AGS gastric xenografts.…”

“…In this context, PET has evolved into immunoPET, wherein antibodies with high specificity for antigens overexpressed or uniquely expressed in tumor cells are labeled with PET radiometals [ 5 , 9 , 10 , 11 , 12 , 13 , 14 ]. In addition to PET, antibodies radiolabeled with single photon emission computed tomography (SPECT) radiometals allow noninvasive, highly sensitive imaging of GC [ 15 , 16 ]. Another attractive antibody-based imaging strategy utilizes comparatively innocuous fluorescent imaging probes that when conjugated to antibodies can be directed specifically to tumor-associated antigens and visualized with high tumor-to-background ratios [ 17 , 18 , 19 , 20 ].…”