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

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.

Proceedings of the National Academy of Sciences of the United States of America. 2016 Sep 29 [Epub ahead of print]

Jovana Golijanin, Ali Amin, Anna Moshnikova, Joseph M Brito, Timothy Y Tran, Ramona-Cosmina Adochite, Gregory O Andreev, Troy Crawford, Donald M Engelman, Oleg A Andreev, Yana K Reshetnyak, Dragan Golijanin

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;, Department of Pathology & Laboratory Medicine, Brown University, The Miriam Hospital, Providence, RI 02906;, Physics Department, University of Rhode Island, Kingston, RI 02881;, Minimally Invasive Urology Institute, Division of Urology, The Miriam Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02906;, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511 ., Physics Department, University of Rhode Island, Kingston, RI 02881; ., Minimally Invasive Urology Institute, Division of Urology, The Miriam Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02906; .

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