2. Academic Validation
  3. Targeting cancer-associated fibroblasts for real-time intraoperative tumor identification with a spray-on fluorescent probe

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

  • Sci Adv. 2025 Nov 21;11(47):eaeb5810. doi: 10.1126/sciadv.aeb5810.
Riley J Deutsch-Williams 1,  Yuxuan Xie 2 3,  Zachary Rabinowitz 1,  Marie Goemans 1,  Pratyaksha Wirapati 3 4,  Claudio Vinegoni 1 5,  Jonathan Ct Carlson 1,  Mikael Pittet 2 3 4 6,  Ralph Weissleder 1 5 7
Affiliations

Affiliations

  • 1 Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St., CPZN 5206, Boston, MA 02114, USA.
  • 2 Department of Pathology and Immunology and Center for Translational Oncohaematology Research, University of Geneva, Geneva, Switzerland.
  • 3 AGORA Cancer Research Center and Swiss Cancer Center Leman, Lausanne, Switzerland.
  • 4 Department of Oncology, Geneva University Hospitals, Geneva, Switzerland.
  • 5 Department of Radiology, Massachusetts General Hospital, 32 Fruit St., Boston, MA 02114, USA.
  • 6 Ludwig Institute for Cancer Research, Lausanne, Switzerland.
  • 7 Department of Systems Biology, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115, USA.
PMID: 41259533 DOI: 10.1126/sciadv.aeb5810
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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