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Targeting cancer-associated fibroblasts for real-time intraoperative tumor identification with a spray-on fluorescent probe

Riley J Deutsch-Williams,Yuxuan Xie,Zachary Rabinowitz,Marie A Goemans,P. Wirapati,Claudio Vinegoni,Jonathan CT Carlson,Mikael J. Pittet,Ralph Weissleder

Published 2025 in Science Advances

ABSTRACT

Surgical tumor resection is often the only curative option for the nearly 20 million newly diagnosed patients with cancer every year. Fluorescence-guided surgery techniques are being developed in an effort to improve margin detection and surgical resection outcomes, with several systemically administered imaging agents having gained clinical approval. However, it has been challenging to overcome limited margin contrast with current approaches and to navigate procedural complexities of intravenous contrast delivery. We hypothesized that “spray-on probes” with specificity for fibroblast activation protein alpha in peritumoral fibroblasts could improve fluorescence-guided surgery, detect smaller tumors, improve imaging accuracy, and reduce the amount of times a patient is hospitalized. We show that this strategy increases achievable tumor margin contrast by 5- to 10-fold and detects even microscopic cancer deposits. These improvements have the potential to transform patient outcomes by enabling more accurate cancer surgeries, reducing the number of follow-up surgeries, and leading to personalized treatment plans.

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