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.
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.
Jovana
J
Golijanin
Department of Pathology & Laboratory Medicine, Brown University, The Miriam Hospital, Providence, RI 02906.
Ali
A
Amin
Physics Department, University of Rhode Island, Kingston, RI 02881.
Anna
A
Moshnikova
Minimally Invasive Urology Institute, Division of Urology, The Miriam Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02906.
Joseph M
JM
Brito
Minimally Invasive Urology Institute, Division of Urology, The Miriam Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02906.
Timothy Y
TY
Tran
Physics Department, University of Rhode Island, Kingston, RI 02881.
Ramona-Cosmina
RC
Adochite
Physics Department, University of Rhode Island, Kingston, RI 02881.
Gregory O
GO
Andreev
Physics Department, University of Rhode Island, Kingston, RI 02881.
Troy
T
Crawford
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511 dgolijanin@lifespan.org reshetnyak@uri.edu donald.engelman@yale.edu.
Donald M
DM
Engelman
Physics Department, University of Rhode Island, Kingston, RI 02881.
Oleg A
OA
Andreev
Physics Department, University of Rhode Island, Kingston, RI 02881; dgolijanin@lifespan.org reshetnyak@uri.edu donald.engelman@yale.edu.
Yana K
YK
Reshetnyak
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.
Dragan
D
Golijanin
D002295:Carcinoma, Transitional Cell / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007208:Indocyanine Green / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D061848:Optical Imaging / Q000379:methods*; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence; D001749:Urinary Bladder Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology
D008565:Membrane Proteins; C533201:pHLIP protein; D007208:Indocyanine Green
NIR imaging; acidity; bladder cancer; fluorescence-guided surgery; human tissue
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