Discussion
tumor, organ malignant neoplasm, organ malignant neoplasms, primary lung cancer, lung cancer, Tumors, lung adenocarcinomas, gastrointestinal malignant neoplasms
IMI, TUMOR, LUNG ADENOCARCINOMA, DISEASE, ADENOCARCINOMAS, MALIGNANT TUMORS, LUNG CANCER, BENIGN TUMORS, SAID, TUMORS
Intraoperative molecular imaging–guided resections have been increasingly added to the armamentarium of solid organ malignant neoplasm resections. However, malignant tumors, particularly in the lung, are heterogonous, which requires exploration of different cellular targeting agents. One such target we explored in this study was the CEACAM5 cell surface glycoprotein, which is expressed in various adenocarcinomas, including colon, rectum, pancreas, esophagogastric, and lung adenocarcinomas.The feasibility and applicability of IMI tracers rely significantly on the clinical utility and ability to use the product in practice daily. Although the CEACAM5 glycoprotein has been extensively studied and validated in the management of various gastrointestinal malignant neoplasms, the same cannot be said in lung cancer.Twenty-two of 33 lung adenocarcinomas (67%) analyzed in our cohort demonstrated CEACAM5 expression by immunohistochemistry, and glycoprotein expression was largely detected in the tumor core itself rather than adjacent normal tissue, which is significant in developing targeted tracers to avoid false positivity (In the control group of patients with metastatic pulmonary nodules, SGM-101 allowed for the in vivo and ex vivo localization of CEACAM5-positive tissues (With the observation that lung parenchyma does not hinder SGM-101’s ability to penetrate pulmonary parenchyma, we explored NIR tracer lesion labeling in patients with pulmonary nodules suggestive of disease. It is our routine institutional practice not to perform diagnostic biopsy for patients with lesions concerning for primary lung cancer and unlike the control cohort did not have preoperative CEACAM5 or diagnosis status. Nevertheless, none of the 2 patients with benign tumors had any fluorescence in vivo, ex vivo, or in histologic assessment. This finding was associated with a lack of CEACAM5, TTF-1, CK 5/6, p63, and Ki-67 staining (Conversely, patients with strong CEACAM5 expression demonstrated fluorescence similar to that of the control group. SGM-101 could be detected in ex vivo analysis colocalized with CEACAM5 staining. Tumors with no CEACAM5 expression as predicted did not demonstrate any fluorescence in any setting. Unlike the control group, most lesions were smaller than 0.75 cm and tended to be deeper in the pulmonary parenchyma. The depth of lesion localization is a known challenge for NIR tracers and correlates with the emission wavelength of the target fluorochrome. With the increasing developments of new fluorochromes that operate in the NIR-II range (>1000 nm), it is expected that deeper parenchyma in solid organ malignant neoplasms can be explored. We demonstrated that the targeted antibody in SGM-101 is highly specific and can potentially be conjugated to a different validated fluorochrome once NIR-II tracers become accessible.