Our long-term objective is to improve the outcomes of patients with high-grade bladder cancer through better diagnostics based on optical imaging. Bladder cancer is the fifth most common cancer in the United States, with 70,980 new cases and 14,330 attributable deaths in 2009. In addition to the associated morbidity of surveillance and treatment, the enormous healthcare burden imposed by bladder cancer makes it the most expensive cancer to treat from diagnosis to death. The current standard for bladder cancer diagnosis relies on white light cystoscopy (WLC) and cystoscopic excisional biopsy for pathologic confirmation and local staging. The quality of optical imaging directly impacts the diagnosis, surveillance, surgery, and consequently the outcome of bladder cancer. WLC has suboptimal diagnostic accuracy for nonpapillary and flat cancerous tumors, which are challenging to differentiate from co-existing inflammatory lesions or scars from prior treatments. Notably, it is these tumors that are more likely to be high-grade, recurrence-prone, and progressive to muscle-invasive disease, which typically require removal of bladder (i.e. radical cystectomy). Our overall hypothesis is that real-time molecular imaging of bladder cancer will lead to improved diagnosis and therapy of high grade bladder cancer. By coupling cancer-specific molecular contrast agents with optical imaging tools, we aim to improve detection of high-grade bladder cancer at an early stage to effect better local cancer control and promote bladder sparing. Towards this goal, we have preliminarily: 1) performed the first clinical application of intravital microscopy in the bladder using confocal laser endomicroscopy;2) applied phage display technology and whole organ biopanning to identify bladder cancer-binding peptides;and 3) identified CD47 as a promising therapeutic and imaging target for bladder cancer. We propose three specific aims: (1) identification and preliminary validation of peptides and CD47 antibody as bladder cancer-specific molecular contrast agents;(2) in vivo validation of the molecular contrast agents in a mouse orthotopic bladder cancer model using confocal laser endomicroscopy;and (3) ex vivo validation of the molecular contrast agents in intact human bladders using confocal laser endomicrocopy. To achieve these aims, we have assembled a multidisciplinary team with complementary expertise in bladder cancer, molecular imaging, small animal cancer models, and optical diagnostics. The team is consisted of an urologic surgeon-scientist, a cancer biologist and an urologic pathologist. We anticipate that at the conclusion of this highly translational project, we will have formed the necessary foundation to begin in vivo validation of these molecular contrast agents for application in human subjects.

Public Health Relevance

Our long-term objective is to improve the outcomes of patients with bladder cancer through better imaging diagnostics. We propose to develop bladder cancer-specific molecular contrast agents for rapid, specific diagnosis of clinically aggressive bladder cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Clinical Molecular Imaging and Probe Development (CMIP)
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Baker, Houston
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Stanford University
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Sin, Mandy L Y; Mach, Kathleen E; Sinha, Rahul et al. (2017) Deep Sequencing of Urinary RNAs for Bladder Cancer Molecular Diagnostics. Clin Cancer Res 23:3700-3710
Chen, Stephanie P; Kirsch, Sarah; Zlatev, Dimitar V et al. (2016) Optical Biopsy of Bladder Cancer Using Crowd-Sourced Assessment. JAMA Surg 151:90-3
Smith, Gennifer T; Lurie, Kristen L; Zlatev, Dimitar V et al. (2016) Multimodal 3D cancer-mimicking optical phantom. Biomed Opt Express 7:648-62
Lopez, Aristeo; Zlatev, Dimitar V; Mach, Kathleen E et al. (2016) Intraoperative Optical Biopsy during Robotic Assisted Radical Prostatectomy Using Confocal Endomicroscopy. J Urol 195:1110-1117
Altobelli, Emanuela; Zlatev, Dimitar V; Liao, Joseph C (2015) Role of Narrow Band Imaging in Management of Urothelial Carcinoma. Curr Urol Rep 16:58
Bui, Daniel; Mach, Kathleen E; Zlatev, Dimitar V et al. (2015) A Pilot Study of In Vivo Confocal Laser Endomicroscopy of Upper Tract Urothelial Carcinoma. J Endourol 29:1418-23
Zlatev, Dimitar V; Altobelli, Emanuela; Liao, Joseph C (2015) Advances in imaging technologies in the evaluation of high-grade bladder cancer. Urol Clin North Am 42:147-57, vii
Chen, Stephanie P; Liao, Joseph C (2014) Confocal laser endomicroscopy of bladder and upper tract urothelial carcinoma: a new era of optical diagnosis? Curr Urol Rep 15:437
Hsu, Mark; Gupta, Mohit; Su, Li-Ming et al. (2014) Intraoperative optical imaging and tissue interrogation during urologic surgery. Curr Opin Urol 24:66-74
Lurie, Kristen L; Smith, Gennifer T; Khan, Saara A et al. (2014) Three-dimensional, distendable bladder phantom for optical coherence tomography and white light cystoscopy. J Biomed Opt 19:36009

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