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Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):11829-11834. Epub 2016 Sep 29.

Targeted imaging of urothelium carcinoma in human bladders by an ICG pHLIP peptide ex vivo.

Author information

1
Minimally Invasive Urology Institute, Division of Urology, The Miriam Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02906; Physics Department, University of Rhode Island, Kingston, RI 02881.
2
Department of Pathology & Laboratory Medicine, Brown University, The Miriam Hospital, Providence, RI 02906.
3
Physics Department, University of Rhode Island, Kingston, RI 02881.
4
Minimally Invasive Urology Institute, Division of Urology, The Miriam Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02906.
5
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511 dgolijanin@lifespan.org reshetnyak@uri.edu donald.engelman@yale.edu.
6
Physics Department, University of Rhode Island, Kingston, RI 02881; dgolijanin@lifespan.org reshetnyak@uri.edu donald.engelman@yale.edu.
7
Minimally Invasive Urology Institute, Division of Urology, The Miriam Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02906; dgolijanin@lifespan.org reshetnyak@uri.edu donald.engelman@yale.edu.

Abstract

Bladder cancer is the fifth most common in incidence and one of the most expensive cancers to treat. Early detection greatly improves the chances of survival and bladder preservation. The pH low insertion peptide (pHLIP) conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets low extracellular pH, allowing visualization of malignant lesions in human bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery were immediately irrigated with nonbuffered saline and instilled with a solution of the ICG pHLIP construct, incubated, and rinsed. Bladders were subsequently opened and imaged, the fluorescent spots were marked, and a standard pathological analysis was carried out to establish the correlation between ICG pHLIP imaging and white light pathological assessment. Accurate targeting of bladder lesions was achieved with a sensitivity of 97%. Specificity is 100%, but reduced to 80% if targeting of necrotic tissue from previous transurethral resections or chemotherapy are considered as false positives. The ICG pHLIP imaging agent marked high-grade urothelial carcinomas, both muscle invasive and nonmuscle invasive. Carcinoma in situ was accurately diagnosed in 11 cases, whereas only four cases were seen using white light, so imaging with the ICG pHLIP peptide offers improved early diagnosis of bladder cancers and may also enable new treatment alternatives.

KEYWORDS:

NIR imaging; acidity; bladder cancer; fluorescence-guided surgery; human tissue

PMID:
27688767
PMCID:
PMC5081621
DOI:
10.1073/pnas.1610472113
[Indexed for MEDLINE]
Free PMC Article

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