Improved Discrimination of Tumors with Low and Heterogeneous EGFR Expression in Fluorescence-Guided Surgery Through Paired-Agent Protocols.

Autor: Wang C; Thayer School of Engineering, Dartmouth College, Hanover, NH, USA., Xu X; Thayer School of Engineering, Dartmouth College, Hanover, NH, USA., Folaron M; Thayer School of Engineering, Dartmouth College, Hanover, NH, USA., Gunn JR; Thayer School of Engineering, Dartmouth College, Hanover, NH, USA., Hodge S; Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA., Chen EY; Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.; Geisel School of Medicine, Dartmouth College, Hanover, NH, USA., Hoopes PJ; Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.; Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.; Geisel School of Medicine, Dartmouth College, Hanover, NH, USA., Tichauer KM; Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA., Samkoe KS; Thayer School of Engineering, Dartmouth College, Hanover, NH, USA. Kimberley.S.Samkoe@dartmouth.edu.; Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. Kimberley.S.Samkoe@dartmouth.edu.; Geisel School of Medicine, Dartmouth College, Hanover, NH, USA. Kimberley.S.Samkoe@dartmouth.edu.
Jazyk: angličtina
Zdroj: Molecular imaging and biology [Mol Imaging Biol] 2023 Feb; Vol. 25 (1), pp. 110-121. Date of Electronic Publication: 2021 Oct 14.
DOI: 10.1007/s11307-021-01656-3
Abstrakt: Purpose: The goal of fluorescence-guided surgery (FGS) in oncology is to improve the surgical therapeutic index by enhancing contrast between cancerous and healthy tissues. However, optimal discrimination between these tissues is complicated by the nonspecific uptake and retention of molecular targeted agents and the variance 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 varied 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.
Procedures: PAI using a fluorescent anti-epidermal growth factor receptor (EGFR) affibody molecule (ABY-029, eIND 122,681) with untargeted IRDye 700DX carboxylate was compared to ABY-029 alone in an oral squamous cell carcinoma xenograft mouse model at 3 h after dye administration (n = 30).
Results: PAI significantly enhanced tumor discrimination, as compared to ABY-029 alone in low EGFR-expressing tumors and highly heterogeneous populations including multiple cell lines with varying expression (diagnostic accuracy: 0.908 vs. 0.854 and 0.908 vs. 0.822; and ROC curve AUC: 0.963 vs. 0.909 and 0.957 vs. 0.909, respectively) indicating a potential for universal FGS image thresholds to determine surgical margins. In addition, PAI achieved significantly higher diagnostic ability than ABY-029 alone 0.25-5-h post injection and exhibited a stronger correlation to EGFR expression heterogeneity.
Conclusion: The quantitative receptor delineation of PAI promises to improve the surgical therapeutic index of cancer resection in a clinically relevant timeline.
(© 2021. The Author(s).)
Databáze: MEDLINE
Externí odkaz: