Oncologic surgery can greatly benefit from imaging techniques for the accurate identification of tumor-positive margins both intraoperatively and in resection specimens immediately following surgery. We have demonstrated clinically that fluorescence lifetime can significantly improve the accuracy for tumor vs. normal classification compared to fluorescence intensity in multiple cancer types using tumor targeted agents. Ongoing efforts by our group towards the translation of fluorescence lifetime imaging for intraoperative image guidance using exogenous agents will also be discussed.
Fluorescence imaging can result in poor tumor contrast due to non-specific probe accumulation of receptor targeted probes. Here we show using preclinical and clinical studies that fluorescence lifetime (FLT) imaging can significantly improve the sensitivity and specificity for tumor detection using epidermal growth factor receptor (EGFR) targeted near infrared probes. We also show that FLTs in tissue are highly correlated with receptor expression levels, thereby enabling quantification of receptor quantification in vivo. Ongoing efforts in our group towards the translation of FLT imaging for intraoperative image guidance during head and neck surgeries will also be discussed.
Precision molecular imaging finds application in the delineation of tumor margins during surgical resection of head and neck cancers (HNCs). Despite the advantages of surgery, there remain challenges in successfully locating tumor margins, resecting the entire tumor volume and treatment of microscopic tumor tissue. The presence of residual tumors, post-surgery, may require additional interventions and often lead to tumor recurrence. While Epidermal growth factor receptor (EGFR) remains a receptor of choice for targeting in HNCs, the heterogeneity in the expression of EGFR often leads to variations in response to targeted therapeutics. To improve visualization and tumor margin delineation during head and neck tumor surgeries, this study demonstrates the development of a molecular targeted theranostic 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 for inducing cytotoxicity, through photodynamic activation in target tissues. The efficacy of DFAC in selective visualization and photodynamic therapy of tumor cells is evaluated on heterocellular 3D tumor spheroids and orthotopic mouse tongue tumors developed from human oral cancer cell lines (CAL27 and SCC4), expressing different levels of EGFR. In summary, this study demonstrates the potential of the theranostic probe (DFAC) to delineate tumor regions for guiding surgical resection and eradicate residual tumor tissue (post-surgery) by photodynamic therapy.
Standard of care in the management of cancer of the oral tongue is complete extirpation with clear margins. There is a direct correlation between the radial margin distance and local failure and death from disease.
Surgical resection of this site is balanced between resection of enough tissue to ensure clear margins and excessive resection that would result in unnecessary oral dysfunction. The optimal margin distance is 5 mm on permanent fixed histological assessment
Mucosal margins are obtained primarily using visual inspection with a reasonable degree of accuracy. More difficult is the deep margin which cannot be seen during the resection, where surgeons must rely on manual palpation to estimate the depth invasion and the needed deep margin tissue thickness.
Over the last three years we have utilized intraoperative ultrasound to improve the likelihood of a clear deep margin. Preliminary analysis has shown that using this technique we are able to reliably clear the deep margin with an improved rate of local control.
Drawing upon our preliminary findings using intraoperative ultrasound for surgical navigation, we have designed a study to employ dual functional antibody conjugates as a theranostic tool to allow molecular based optical imaging of tumor margins, improving precision of the resection and utilizing a benzoporphyrin derivative to provide for a tumor specific photodynamic therapy treatment at the time of resection.
Techniques and preliminary oncologic and margin outcomes of intraoperative ultrasound as well as the concepts of the use of dual functional antibody conjugates in surgical navigation will be discussed.
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