Leslie Contreras with Dr. Tayyaba Hasan (MGH)
Precision imaging is an important tool in cancer management, mostly employed in diagnostics, treatment planning, optimization, and monitoring response to therapy. An important application where precision imaging has played an important role is guidance, during surgical resection of tumors, to delineate tumor margins. Amongst current, standard treatments of cancer including radiation, surgery, and chemotherapy, surgery is the most widely used method of treatment due to its high efficacy. Despite the advantages of surgery, there remain challenges in successfully locating tumor margins and resecting the entire tumor volume, including smaller masses. The presence of residual tumors, post-surgery, may require additional interventions and often lead to tumor recurrence. Therefore, in order to improve visualization and tumor margin delineation during surgery, this project aims at developing a molecular targeted multi-modal imaging probe combining the complementary features of fluorescence and photoacoustic imaging. The probe: DFAC (Dual Function Antibody Conjugate) comprises of a fluorophore/photosensitizer; Benzoporphyrin derivative (BPD) and a photoacoustic contrast agent; naphthalocyanine (NC) derivative conjugated to an EGFR antibody; Cetuximab. While BPD assists in fluorescence imaging, it can also be used as a photosensitizer for inducing cytotoxicity, through photodynamic activation, in the target tissues. The efficacy of DFAC, in selective visualization and photodynamic therapy of tumor cells, will be evaluated on 3D tumor spheroid models developed from human oral cancer cell lines (CAL27 and SCC9), which express different levels of EGFR. The overarching goal of this study is to develop a theranostic probe with potential application in surgical guidance and photodynamic therapy of residual tumor tissue.
