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Dual‐agent fluorescent labeling of soft‐tissue sarcomas improves the contrast based upon targeting both interstitial and cellular components of the tumor milieu
Author(s) -
Sardar Hira S.,
Zai Qais,
Xu Xiaochun,
Gunn Jason R.,
Pogue Brian W.,
Paulsen Keith D.,
Henderson Eric R.,
Samkoe Kimberley S.
Publication year - 2020
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.26190
Subject(s) - indocyanine green , medicine , fluorescence , homogeneous , contrast (vision) , fluorescence lifetime imaging microscopy , molecular imaging , nuclear medicine , pathology , in vivo , biology , physics , microbiology and biotechnology , quantum mechanics , artificial intelligence , computer science , thermodynamics
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 μg/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 ( ρ = 0.2 ± 0.4), while ICG demonstrated a strong negative correlation ( ρ = −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 ( ρ = −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.