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SGM-101: An innovative near-infrared dye-antibody conjugate that targets CEA for fluorescence-guided surgery
Marian Gutowski1, Bérénice Framery2, Martin C Boonstra3
1Institut régional du Cancer de Montpellier, ICM, Montpellier, F-34298, France.
Purpose:
Fluorescence-guided surgery (FGS) provides surgeons with new opportunities to improve real-time cancer nodule detection and tumor margin visualization. Currently, the most important challenge in this field is the development of fluorescent dyes that specifically target tumors. We developed, characterized and evaluated SGM-101, an innovative antibody-dye conjugate in which the fluorochrome BM104, which has an absorbance band centered at 700 nm, is coupled to a chimeric monoclonal antibody (mAb) against carcinoembryonic antigen (CEA).
Methods:
The dye to mAb ratio, binding to CEA and photobleaching of SGM-101 were determined. FGS was performed and results analyzed using different mouse models of human digestive tumors.
Results:
SGM-101 allowed the detection of tumor nodules in three different colon cancer models: LS174T human colorectal adenocarcinoma cell-induced peritoneal carcinomatosis (PC) and liver metastases, and orthotopic grafts of HT29 human colorectal adenocarcinoma cells. In the PC model, submillimeter-sized nodules were detected during SGM-101-based FGS and SGM-101 predictive positive values ranged from 99.04% to 90.24% for tumor nodules >10 mg and nodules <1 mg, respectively. Similarly, in the orthotopic model of pancreatic cancer using BxPC3 (pancreas adenocarcinoma) cells, SGM-101 could clearly delineate tumors in vivo with a tumor-to-background ratio of 3.5, and penetrated in tumor nodules, as demonstrated by histological analysis. Free BM105 dye (BM104 with an activated ester for conjugation to the antibody) and an irrelevant conjugate did not induce any NIR fluorescence.
Conclusion:
These preclinical data indicate that SGM-101 is an attractive candidate for FGS of CEA-expressing tumors and is currently assessed in clinical trials.
Insights
SGM-101, a novel fluorescent dye targeting CEA, effectively detects small tumors in preclinical models. This antibody-dye conjugate shows promise for improving cancer surgery visualization.
Area of Science:
- Oncology
- Surgical Oncology
- Bioconjugation Chemistry
Background:
- Fluorescence-guided surgery (FGS) enhances real-time cancer detection and margin visualization.
- A key challenge in FGS is developing tumor-specific fluorescent dyes.
- Carcinoembryonic antigen (CEA) is a target for certain cancers.
Purpose of the Study:
- To develop, characterize, and evaluate SGM-101, an antibody-dye conjugate for FGS.
- SGM-101 targets CEA, utilizing the fluorochrome BM104 (absorbance peak at 700 nm).
- To assess SGM-101's efficacy in detecting digestive tumors in preclinical models.
Main Methods:
- SGM-101 was characterized for dye-to-antibody ratio, CEA binding, and photobleaching.
- Fluorescence-guided surgery was performed using mouse models of human digestive tumors.
- Tumor detection and delineation capabilities were analyzed in peritoneal carcinomatosis and orthotopic pancreatic cancer models.
Main Results:
- SGM-101 successfully detected tumor nodules in colon cancer models (peritoneal carcinomatosis and liver metastases).
- Submillimeter nodules were detected in the peritoneal carcinomatosis model with high predictive positive values.
- In pancreatic cancer models, SGM-101 delineated tumors in vivo with a high tumor-to-background ratio and demonstrated tumor penetration.
Conclusions:
- SGM-101 demonstrates significant potential as a fluorescent agent for FGS of CEA-expressing tumors.
- Preclinical data suggest SGM-101's effectiveness in visualizing small tumor nodules and margins.
- SGM-101 is currently undergoing evaluation in clinical trials.
