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Journal of Surgical Oncology 2019-Jun

Preclinical imaging of epidermal growth factor receptor with ABY-029 in soft-tissue sarcoma for fluorescence-guided surgery and tumor detection.

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Kimberley Samkoe
Hira Sardar
Brent Bates
Niki Tselepidakis
Jason Gunn
Kevin Hoffer-Hawlik
Joachim Feldwisch
Brian Pogue
Keith Paulsen
Eric Henderson

Mots clés

Abstrait

BACKGROUND AND OBJECTIVES
Fluorescence-guided surgery using epidermal growth factor receptor (EGFR) targeting has been performed successfully in clinical trials using a variety of fluorescent agents. We investigate ABY-029 (anti-EGFR Affibody® molecule labeled with IRDye 800CW) compared with a small-molecule perfusion agent, IRDye 700DX carboxylate, in a panel of soft-tissue sarcomas with varying levels of EGFR expression and vascularization.

Five xenograft soft-tissue sarcoma cell lines were implanted into immunosuppressed mice. ABY-029 and IRDye 700DX were each administered at 4.98 μM. Fluorescence from in vivo and ex vivo (fresh and formalin-fixed) fixed tissues were compared. The performance of three fluorescence imaging systems was assessed for ex vivo tissues.ABY-029 is retained longer within tumor tissue and achieves higher tumor-to-background ratios both in vivo and ex vivo than IRDye 700DX. ABY-029 fluorescence is less susceptible to formalin fixation than IRDye 700DX, but both agents have disproportional signal loss in a variety of tissues. The Pearl Impulse provides the highest contrast-to-noise ratio, but all systems have individual advantages.ABY-029 demonstrates promise to assist in wide local excision of soft-tissue sarcomas. Further clinical evaluation of in situ or freshly excised ex vivo tissues using fluorescence imaging systems is warranted.

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