Oral cancer surgeons are faced with a difficult task during tumor resection, as they must find a balance between removing all tumor tissue to prevent recurrence, while also minimizing healthy tissue resection to prevent disfigurement and co-morbidities¹. To aid in determining accurate tumor dimensions and guide resection surgeries, physicians use precision fluorescence imaging with fluorophores (e.g. ICG, 5-ALA)¹. While this technique is better than just white light imaging, there is limited tumor-to-background contrast due to non-specific dye accumulation. In addition, adjuvant therapies post-surgery (such as chemo and radiation therapies) are used to minimize recurrence. Blocking EGFR (over-expressed in oral cancer cells), by anti-EGFR antibodies such as Cetuximab, is also used in oral cancer management post-surgery. More recently, conjugating free fluorescent dyes to Cetuximab to create a fluorophore antibody conjugate has been used in the clinic to improve tumor-to-background ratio. However, fluorophores can only assist in superficial identification of tumor margins, with limited depth profiling. Combining molecular targeted fluorophores with sonochromes can overcome the limited depth profiling of these conjugates by complementary photoacoustic imaging. Although the imaging contrast through multimodal imaging can assist in identification of tumor margins with greater precision, the possibility of leaving behind microscopic diseases still exists. In this context the use of Benzoporphyrin derivative (BPD) as a fluorophore and photosensitizer can assist in imaging and photoimmunotherapy of microscopic disease, after surgical resection, in a single intraoperative setting. In this research project, a target-specific multimodal molecular imaging probe called “Dual Function Antibody Conjugate (DFAC)” is developed and evaluated in vitro for its efficacy to detect and treat EGFR-positive oral tumors. It is comprised of BPD (fluorophore and photosensitizer) and a naphthalocyanine-derived PA contrast agent (SiNc(OH)) conjugated to Cetuximab⁴, which will be tested in a preclinical setting in 3D cell culture models using the human oral cancer cell line CAL27. Overall, the goal of this research project is to determine if DFAC can be used in a single intraoperative setting, to enhance precision imaging of tumor margins and photoimmunotherapy to enhance treatment outcomes in oral cancers.

References

1. Ghanim, M. et al. A non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds. Sci Rep 11, 14069 (2021).
2. Gao, R. W. et al. Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers. Theranostics 8, 2488–2495 (2018).
3. De Silva, P. et al. Photodynamic therapy, priming and optical imaging: Potential co-conspirators in treatment design and optimization — a Thomas Dougherty Award for Excellence in PDT paper. J. Porphyrins Phthalocyanines 24, 1320–1360 (2020).
4. Saad, M. A. et al. Dual Function Antibody Conjugates for Multimodal Imaging and Photoimmunotherapy of Cancer Cells. Photochem & Photobiology 98, 220–231 (2022)