T. Ramesh1, L. Moore1, S. Bevans1, M. Limdi1, E. Rosenthal2, J. Warram1 1University Of Alabama,School Of Medicine,Birmingham, Alabama, USA 2Stanford University,School Of Medicine,Palo Alto, CA, USA
Introduction:
The integrin avb3 is overexpressed in pathologic processes associated with tumor growth and invasion, including in tumor cells and angiogenic blood vessels. IntegriSense 750 (Perkin Elmer) is a targeted fluorescent imaging agent composed of a selective av?b3 antagonist and a near-infrared fluorochrome. We hypothesize IntegriSense 750 can effectively produce contrast for applications in fluorescence-guided surgery as demonstrated in flank xenograft, orthotopic tongue, and lymph node metastatic disease models of head and neck cancer. A dose escalation study was performed at three doses (1.25μg/mouse, 2.5μg/mouse, and 5μg/mouse) in mice bearing luc+ SCC1 flank xenografts (n=5). Mice bearing orthotopic tongue (n=3) and lymph node (n=3) models received 2.5μg of IntegriSense 750 per mouse.
Methods:
Fluorescence imaging was performed twice daily after infusion using commercially available open-field NIR and closed-field NIR imaging systems. NIR renderings of resected specimens were compared to bioluminescence images to confirm localization of probe to tumor. Tissue fluorescence was correlated with histology. Progressively smaller tumor fragments were re-introduced into the wound bed in order to determine the smallest cancerous mass detectable using this agent. Exploratory surgeries were performed to demonstrate agent localization to orthotopic tumors and lymph node metastases. A biodistribution study was performed four days after dosing.
Results:
Intraoperative imaging successfully differentiated tumor from normal tissue with mean tumor-to-background ratios of 3.73, 5.35, and 9.62 on day 4 for the 1.25μg, 2.5μg, and 5μg doses, respectively. Tumor-to-background ratios for all three groups peaked at four days post-infusion. Tumor fragments as small as 0.5mg were visualized in all three dosing cohorts. 3/3 diseased lymph nodes were fluorescently visible in situ in mice during exploratory surgeries. The 5μg dose was found to be the optimal dose for applications in fluorescence-guided surgical oncology in this study.
Conclusion:
IntegriSense 750 appeared to be effective for use in fluorescence-guided surgical applications as demonstrated in flank xenograft, orthotopic, and lymph node metastatic disease models of head and neck cancer.