Research ArticleCancer Imaging

A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer

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Science Translational Medicine  06 Jan 2016:
Vol. 8, Issue 320, pp. 320ra4
DOI: 10.1126/scitranslmed.aad0293

Protease probe tested in humans

Cancer cells secrete more of the protease cathepsin than healthy cells, partly as a way to enzymatically remodel their surroundings for tumor growth and metastasis. Whitley et al. developed an imaging probe that could be activated in the presence of these cathepsins, thus allowing surgeons to distinguish tumor margins intraoperatively. Their probe, called LUM015, was able to signal the presence of cancer in vivo in a mouse sarcoma model, and in a so-called “co-clinical trial” in 15 patients, it was safe and cleaved as expected in different types of tumor tissues. With favorable biodistribution and pharmacokinetics also demonstrated, protease-activated probes are now poised for further adaptation to tumor resections, signaling the presence of residual cancer.

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