Engineering Bacterial Secretion Systems for Enhanced Tumor Imaging and Surgical Guidance

Area of Science:

• Biomedical Imaging
• Surgical Oncology
• Microbial Therapeutics

Background:

• Current imaging lacks specificity and resolution, hindering accurate tumor detection and surgical guidance.
• Existing contrast agents face limitations in tumor-to-background ratio (TBR), signal duration, and deep tissue penetration.
• Need for advanced imaging solutions for precise surgical margin delineation.

Purpose of the Study:

• To develop and evaluate a novel contrast agent for enhanced image-guided cancer surgery.
• To assess the efficacy of Streptavidin Associated Salmonella (SAS) in improving tumor visualization and surgical precision.

Main Methods:

• Utilized Streptavidin Associated Salmonella (SAS), a genetically engineered bacteria, as a novel contrast agent.
• SAS selectively proliferates in cancerous tissues and secretes streptavidin upon induction.
• Administered biotin-conjugated fluorescent dyes for visualization, enabling prolonged imaging and deep tumor penetration.

Main Results:

• Achieved a significantly enhanced tumor-to-background ratio (TBR) of up to 15.3, compared to conventional agents (TBR ~ 2).
• Enabled prolonged 3-day imaging and precise delineation of invasive margins with a single injection.
• Biosafety evaluations confirmed efficient bacterial clearance, no systemic toxicity, and stable physiological responses.

Conclusions:

• SAS offers a promising novel approach for image-guided cancer surgery, overcoming limitations of current fluorescent contrast agents.
• The method provides superior tumor visualization, prolonged imaging, and deep tissue penetration for improved surgical outcomes.
• Demonstrated potential for safe clinical translation in both diagnostic and therapeutic applications.