Optical Imaging of Bladder Cancer with Molecular Contrast Agents

Summary

Principal Investigator: Joseph C Liao
Abstract: DESCRIPTION (provided by applicant): 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.
Funding Period: 2011-08-01 - 2015-05-31
more information: NIH RePORT

Top Publications

  1. pmc New optical imaging technologies for bladder cancer: considerations and perspectives
    Jen Jane Liu
    Department of Urology, Stanford University School of Medicine, Stanford, California, USA
    J Urol 188:361-8. 2012
  2. pmc Interobserver agreement of confocal laser endomicroscopy for bladder cancer
    Timothy C Chang
    Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA
    J Endourol 27:598-603. 2013
  3. pmc Intraoperative optical imaging and tissue interrogation during urologic surgery
    Mark Hsu
    aDepartment of Urology, Stanford University School of Medicine, Stanford, California, USA bDepartment of Urology, University of Florida College of Medicine, Gainsville, Florida, USA cVeterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA
    Curr Opin Urol 24:66-74. 2014
  4. pmc Three-dimensional, distendable bladder phantom for optical coherence tomography and white light cystoscopy
    Kristen L Lurie
    Stanford University, Department of Electrical Engineering, Stanford, California 94305
    J Biomed Opt 19:36009. 2014
  5. pmc Emerging endoscopic imaging technologies for bladder cancer detection
    Aristeo Lopez
    Department of Urology, Stanford University School of Medicine, 300 Pasteur Dr, Room S 387, Stanford, CA, 94305 5118, USA
    Curr Urol Rep 15:406. 2014

Research Grants

  1. NUCLEAR STRUCTURE AND GENE EXPRESSION
    Janet L Stein; Fiscal Year: 2013

Detail Information

Publications7

  1. pmc New optical imaging technologies for bladder cancer: considerations and perspectives
    Jen Jane Liu
    Department of Urology, Stanford University School of Medicine, Stanford, California, USA
    J Urol 188:361-8. 2012
    ..We analyzed the added value of each technology beyond white light cystoscopy and evaluated their maturity to alter the cancer course...
  2. pmc Interobserver agreement of confocal laser endomicroscopy for bladder cancer
    Timothy C Chang
    Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA
    J Endourol 27:598-603. 2013
    ..The purpose of this study was to determine the interobserver agreement of image interpretation using CLE for bladder cancer...
  3. pmc Intraoperative optical imaging and tissue interrogation during urologic surgery
    Mark Hsu
    aDepartment of Urology, Stanford University School of Medicine, Stanford, California, USA bDepartment of Urology, University of Florida College of Medicine, Gainsville, Florida, USA cVeterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA
    Curr Opin Urol 24:66-74. 2014
    ..To review optical imaging technologies in urologic surgery aimed to facilitate intraoperative imaging and tissue interrogation...
  4. pmc Three-dimensional, distendable bladder phantom for optical coherence tomography and white light cystoscopy
    Kristen L Lurie
    Stanford University, Department of Electrical Engineering, Stanford, California 94305
    J Biomed Opt 19:36009. 2014
    ..We anticipate that this phantom will be immediately useful to evaluate innovative OCT systems and software being developed for longitudinal bladder surveillance and early cancer detection...
  5. pmc Emerging endoscopic imaging technologies for bladder cancer detection
    Aristeo Lopez
    Department of Urology, Stanford University School of Medicine, 300 Pasteur Dr, Room S 387, Stanford, CA, 94305 5118, USA
    Curr Urol Rep 15:406. 2014
    ..We review their mechanisms of action, highlight their respective advantages, and propose future directions. ..

Research Grants30

  1. NUCLEAR STRUCTURE AND GENE EXPRESSION
    Janet L Stein; Fiscal Year: 2013
    ..abstract_text> ..