Real-Time Detection of Colorectal Cancer Using Topical Application of a pH-Activatable Fluorophore

  • Mol Diagn Ther. 2026 Jul;30(4):689-706. doi: 10.1007/s40291-026-00853-6.
Daan G J Linders  #  1 ,  Jinhui Ser  #  2 ,  Md Shamim  3 ,  Aida Baibussunova  2 ,  Jasmijn C J Loggers  1 ,  Gilbert Noordam  4 ,  Davey van den Burg  4 ,  Gijs J D van Acker  5 ,  Onno R Guicherit  5 ,  Marinke Westerterp  5 ,  Peter J K Kuppen  1 ,  Andreas W K S Marinelli  5 ,  Denise E Hilling  1  6 ,  Elke E M Peters  4 ,  Satoshi Kashiwagi  7 ,  Maged Henary  8 ,  Hak Soo Choi  9 ,  Alexander L Vahrmeijer  10
Affiliations
  • 1. Department of Surgery, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
  • 2. Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
  • 3. Department of Chemistry, Center of Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30303, USA.
  • 4. Department of Pathology, Haaglanden Medical Center, 2512 VA, The Hague, The Netherlands.
  • 5. Department of Surgery, Haaglanden Medical Center, 2512 VA, The Hague, The Netherlands.
  • 6. Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 GD, Rotterdam, The Netherlands.
  • 7. Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. [email protected].
  • 8. Department of Chemistry, Center of Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30303, USA. [email protected].
  • 9. Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. [email protected].
  • 10. Department of Surgery, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands. [email protected].
  • # Contributed equally.
PMID: 42174369 DOI: 10.1007/s40291-026-00853-6
Abstract

Introduction: Standard treatment for locally advanced rectal Cancer involves neoadjuvant chemoradiation therapy (nCRT) followed by total mesorectal excision, but this approach carries significant morbidity and often results in incomplete resections owing to poor intraoperative tumor visualization. For patients with complete response to nCRT, a watch-and-wait (W&W) strategy can spare surgery, but current imaging techniques inadequately identify complete responders, leading to regrowth in ~ 30% of cases. To improve nCRT response assessment and guide resections, we developed PH10, a topically applied, pH-activatable near-infrared (NIR) fluorescent probe for rapid, tumor-specific imaging.

Methods: PH10, a small-molecule cyanine analog, was tested in murine models and on human tumor specimens (n = 11). Fluorescence activation, tumor specificity, and tumor-to-background ratio (TBR) were evaluated in vivo and ex vivo within clinically relevant timeframes.

Results: PH10 enabled rapid and specific tumor visualization, achieving a median TBR of 3.2 within 1 min in vivo in murine models and 2.2 within 10 min ex vivo on human samples. The probe demonstrated high specificity for tumor tissue within the acidic tumor microenvironment without requiring systemic administration or prolonged incubation.

Conclusions: PH10 is a promising, fast-acting topical NIR agent for real-time tumor detection during Colorectal Cancer endoscopy and surgery. Its simplicity and rapid kinetics support potential clinical translation. Moreover, its pH-activatable mechanism may extend its utility to other solid cancers with acidic microenvironments.

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