Simultaneous In Vivo Fluorescent Markers for Perfusion, Protoporphyrin Metabolism, and EGFR Expression for Optically Guided Identification of Orthotopic Glioma

Human use of ABY-029 for glioma resection should enhance excision of EGFR+ tumors and could be incorporated into current PpIX strategies to further enhance treatment in the general glioma case. Clin Cancer Res; 23(9); 2203-12. ©2016 AACR.

While extent of tumor resection is an important predictor of outcome in glioma, margin delineation remains challenging due to lack of inherent contrast between tumor and normal parenchyma. Fluorescence-guided surgery is promising for its ability to enhance contrast through exogenous fluorophores; however, the specificity and sensitivity of the underlying contrast mechanism and tumor delivery and uptake vary widely across approved and emerging agents.Experimental Design: Rats with orthotopic F98 wild-type and F98 EGFR-positive (EGFR+) gliomas received in vivo administration of IRDye680RD, 5-aminioleuvulinic acid, and ABY-029-markers of perfusion, protoporphyrin metabolism, and EGFR expression, respectively. Ex vivo imaging demonstrates the contrast mechanism-dependent spatial heterogeneity and enables within-animal comparisons of tumor-to-background ratio (TBR).

Generally, ABY-029 outperformed PpIX in F98EGFR orthotopic tumor margins and core (50% and 60% higher TBR, respectively). PpIX outperformed ABY-029 in F98wt margins by 60% but provided equivalent contrast in the bulk tumor. IRDye680RD provided little contrast, having an average TBR of 1.7 ± 0.2. The unique spatial patterns of each agent were combined into a single metric, the multimechanistic fluorescence-contrast index (MFCI). ABY-029 performed best in EGFR+ tumors (91% accuracy), while PpIX performed best in wild-type tumors (87% accuracy). Across all groups, ABY-029 and PpIX performed similarly (80% and 84%, respectively) but MFCI was 91% accurate, supporting multiagent imaging when tumor genotype was unknown.Conclusions: Human use of ABY-029 for glioma resection should enhance excision of EGFR+ tumors and could be incorporated into current PpIX strategies to further enhance treatment in the general glioma case. Clin Cancer Res; 23(9); 2203-12. ©2016 AACR.