Dual-agent fluorescent labeling of soft-tissue sarcomas improves the contrast based upon targeting both interstitial and cellular components of the tumor milieu

摘要

Background Current practices for fluorescence-guided cancer surgery utilize a single fluorescent agent, but homogeneous distribution throughout the tumor is difficult to achieve. We hypothesize that administering a perfusion and a molecular-targeted agent at their optimal administration-to-imaging time will improve whole-tumor contrast. Experimental Design Mice bearing subcutaneous xenograft human synovial sarcomas were administered indocyanine green (ICG) (3 mg/kg) or ABY-029 (48.7 mu g/kg)-an epidermal growth factor receptor-targeted Affibody molecule-alone or in combination. Fluorescence contrast and signal distribution were compared between treatment groups. Two commercial fluorescence imaging systems were tested for simultaneous imaging of ICG and ABY-029. Results ABY-029 has a moderate positive correlation with viable tumor (rho = 0.2 +/- 0.4), while ICG demonstrated a strong negative correlation (rho = -0.6 +/- 0.1). The contrast-to-variance ratio was highest in the ABY-029 +ICG (2.5 +/- 0.8), compared to animals that received ABY-029 (2.3 +/- 0.8) or ICG (2.0 +/- 0.5) alone. Moreover, the combination of ABY-029 + ICG minimizes the correlation between viable tumor and fluorescence intensity (rho = -0.1 +/- 0.2) indicating the fluorescence signal distribution is more homogeneous throughout the tumor milieu. Conclusion Dual-agent imaging utilizing a single channel in a commercial fluorescence-guided imaging system tailored for IRDye 800CW is a promising method to increase tumor contrast in a clinical setting.