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• W3111446471 abstract "Abstract Background: The goal of fluorescence guided surgery (FGS) in oncology is to improve the surgical therapeutic index by enhancing contrast between cancerous and healthy tissue. However, optimal discrimination between these tissues is complicated by the non-specific uptake and retention of molecular targeted agents and the heterogeneity of fluorescence signal. Paired-agent imaging (PAI) employs co-administration of an untargeted imaging agent with a molecular targeted agent, providing a normalization factor to minimize nonspecific and heterogeneous signals. The resulting measured binding potential is quantitative and equivalent to in vivo immunohistochemistry of the target protein. This study demonstrates that PAI improves the accuracy of tumor-to-healthy tissue discrimination compared to single agent imaging for in vivo FGS. Methods: PAI using a fluorescent anti-EGFR affibody molecule (ABY-029, eIND 122681) with untargeted IRDye 700DX carboxylate was compared to ABY-029 alone in an oral squamous cell carcinoma xenograft mouse model at 3 hours ( n = 30). Results: PAI significantly enhanced tumor discrimination, as compared to ABY-029 alone (diagnostic accuracy - 0.94 vs 0.86, ROC curve AUC - 0.991 vs. 0.925, respectively). Additionally, the AUC of the ROC curve for PAI was stable as patient cohort number was increased from n = 1 to 20, while ABY-029 decreased as n increased, indicating a potential for universal FGS image thresholds to determine surgical margins. In addition, PAI reduced the administration-to-imaging time from 3 hours to 30 minutes and exhibited a statistically stronger correlation to EGFR expression heterogeneity ( r = 0.58 compared to r = 0.47, p = 9B10 -8 ). Conclusion: The quantitative receptor delineation of PAI promises to improve the surgical therapeutic index of cancer resection in a clinically relevant timeline." @default.
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• W3111446471 date "2020-11-20" @default.
• W3111446471 modified "2023-09-27" @default.
• W3111446471 title "Improved Tumor Discrimination and Shortened Administration-to-Imaging Times in Fluorescence Guided Surgery Through Paired-Agent Protocols" @default.
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• W3111446471 doi "https://doi.org/10.21203/rs.3.rs-111011/v1" @default.
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