Antibody-Targeted Imaging of Gastric Cancer

Mandleywala, Komal; Shmuel, Shayla; Pereira, Patrícia M. R.; Lewis, Jason S.

doi:10.3390/molecules25204621

Cited by 8 publications

(6 citation statements)

References 57 publications

(104 reference statements)

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“…37 In gastric cancer, a few probes have been evaluated for fluorescence labeling of tumors in preclinical models, although currently, none are FDA-approved for use in FGS. 38 cell lines) compared with a control antibody. 41 There are significant challenges with probe selection for gastric cancer; EGFR expression is only seen in 62% of gastric cancers, and although MG7 is expressed in 94% of gastric cancers, it also is seen in Helicobacter pylori-associated gastritis.…”

Section: Discussionmentioning

confidence: 99%

Targeting Patient-Derived Orthotopic Gastric Cancers with a Fluorescent Humanized Anti-CEA Antibody

Cox,

Turner,

Lwin

et al. 2024

Ann Surg Oncol

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Background Gastric cancer poses a major diagnostic and therapeutic challenge as surgical resection provides the only opportunity for a cure. Specific labeling of gastric cancer could distinguish resectable and nonresectable disease and facilitate an R0 resection, which could improve survival. Methods Two patient-derived gastric cancer lines, KG8 and KG10, were established from surgical specimens of two patients who underwent gastrectomy for gastric adenocarcinoma. Harvested tumor fragments were implanted into the greater curvature of the stomach to establish patient-derived orthotopic xenograft (PDOX) models. M5A (humanized anti-CEA antibody) or IgG control antibodies were conjugated with the near-infrared dye IRDye800CW. Mice received 50 µg of M5A-IR800 or 50 µg of IgG-IR800 intravenously and were imaged after 72 hr. Fluorescence imaging was performed by using the LI-COR Pearl Imaging System. A tumor-to-background ratio (TBR) was calculated by dividing the mean fluorescence intensity of the tumor versus adjacent stomach tissue. Results M5A-IR800 administration resulted in bright labeling of both KG8 and K10 tumors. In the KG8 PDOX models, the TBR for M5A-IR800 was 5.85 (SE ± 1.64) compared with IgG-IR800 at 0.70 (SE ± 0.17). The K10 PDOX models had a TBR of 3.71 (SE ± 0.73) for M5A-IR800 compared with 0.66 (SE ± 0.12) for IgG-IR800. Conclusions Humanized anti-CEA (M5A) antibodies conjugated to fluorescent dyes provide bright and specific labeling of gastric cancer PDOX models. This tumor-specific fluorescent antibody is a promising potential clinical tool to detect the extent of disease for the determination of resectability as well as to visualize tumor margins during gastric cancer resection.

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Section: Discussionmentioning

confidence: 99%

Targeting Patient-Derived Orthotopic Gastric Cancers with a Fluorescent Humanized Anti-CEA Antibody

Cox,

Turner,

Lwin

et al. 2024

Ann Surg Oncol

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“…Radiolabeled rilotumumab (anti-HGF mAb) and onartuzumab (anti-MET mAb) non-invasively detected HGF and MET expression, respectively ( 244 , 245 ). Additionally, MG7, a gastric cancer-specific antigen, is a prognostic biomarker ( 78 ). PET imaging of anti-MG7 Abs in gastric cancer xenografts showed a favorable binding affinity ( 246 ), but its application may be limited due to the overexpression of MG7 in helicobacter-related gastric disease ( 247 ).…”

Section: Immunopet In Different Malignanciesmentioning

confidence: 99%

ImmunoPET: Antibody-Based PET Imaging in Solid Tumors

et al. 2022

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Immuno-positron emission tomography (immunoPET) is a molecular imaging modality combining the high sensitivity of PET with the specific targeting ability of monoclonal antibodies. Various radioimmunotracers have been successfully developed to target a broad spectrum of molecules expressed by malignant cells or tumor microenvironments. Only a few are translated into clinical studies and barely into clinical practices. Some drawbacks include slow radioimmunotracer kinetics, high physiologic uptake in lymphoid organs, and heterogeneous activity in tumoral lesions. Measures are taken to overcome the disadvantages, and new tracers are being developed. In this review, we aim to mention the fundamental components of immunoPET imaging, explore the groundbreaking success achieved using this new technique, and review different radioimmunotracers employed in various solid tumors to elaborate on this relatively new imaging modality.

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“…Although the invention of new types of endoscopies provided useful tools for tumor diagnosis, the accurate tool for EGC diagnosis is still lacking; therefore, there is a very urgent need to find an endoscopic method for EGC diagnosis that is easy and independent from the operator. Antibodies conjugated with fluorescent dyes can image tumors by targeted optical imaging (20), the fluorescent probe is a new method that can visualize tumors (21). It was found the novel zinc ion fluorescent probe DPP-C2 showed potential application for the early detection of prostate cancer in tumorbearing nude mice (22).…”

Section: The Ceacam6 -Mab-irdye800cw Can Track the Tumor As Well As Metastases In Vivomentioning

confidence: 99%

Carcinoembryonic Antigen Related Cell Adhesion Molecule 6 Promotes Carcinogenesis of Gastric Cancer and Anti-CEACAM6 Fluorescent Probe Can Diagnose the Precancerous Lesions

Zheng

Zhang

et al. 2021

Front. Oncol.

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The diagnosis of precancerous lesions or early gastric cancer (EGC) is very important for patient survival. Molecular imaging is a visualized method that can easily and precisely diagnose tumors. However, there are currently few studies about molecular imaging diagnosis of EGC. Here, we studied the expression of carcinoembryonic antigen related cell adhesion molecule 6 (CEACAM6) in the progression of GC. Then, the regulatory roles of CEACAM6 in GC cells were investigated. Furthermore, both the fluorescent-labeled and near infrared molecular-labeled probes were synthesized, and the diagnostic value of anti-CEACAM6 probes in GC was evaluated in vivo using a GC mice model as well as in vitro using fresh dysplastic gastric mucosa obtained from endoscopic submucosal dissection (ESD) operations. Our study showed that CEACAM6 was over expressed in GC tissues compared to adjacent tissues, and the patients with higher CEACAM6 expression had lower survival time. Moreover, the CEACAM6 expression was higher in the dysplastic gastric mucosa than in the adjacent normal mucosa. CEACAM6 accelerated the growth, proliferation, and invasion of GC cells in the in vitro and in vivo studies. Moreover, up regulated CEACAM6 can induce the expression of proteins related to GC progression. Furthermore, the anti-CEACAM6 probes exhibited good affinity with GC cell lines. The probes can track tumors as well as metastases in the mice model in vivo, and can precisely identify the area of dysplastic gastric mucosa using specimens obtained from ESD operations by wide field fluorescent endoscopy. The surface micro features of the mucosa can also be observed using fluorescent micro endoscopy, and the degree of atypia can be distinguished by both the signal intensity and surface micro morphology. CEACAM6 is a key molecular marker in GC progression, and the anti-CEACAM6 probe-assisted fluorescent endoscopy may be a potential option for the diagnosis of precancerous lesions.

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Antibody-Targeted Imaging of Gastric Cancer

Cited by 8 publications

References 57 publications

Targeting Patient-Derived Orthotopic Gastric Cancers with a Fluorescent Humanized Anti-CEA Antibody

Targeting Patient-Derived Orthotopic Gastric Cancers with a Fluorescent Humanized Anti-CEA Antibody

ImmunoPET: Antibody-Based PET Imaging in Solid Tumors

Carcinoembryonic Antigen Related Cell Adhesion Molecule 6 Promotes Carcinogenesis of Gastric Cancer and Anti-CEACAM6 Fluorescent Probe Can Diagnose the Precancerous Lesions

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