Phage Display-Derived Peptide-Based Dual-Modality Imaging Probe for Bladder Cancer Diagnosis and Resection Postinstillation: A Preclinical Study

Mol Cancer Ther. 2018 Oct;17(10):2100-2111. doi: 10.1158/1535-7163.MCT-18-0212. Epub 2018 Aug 6.

Abstract

Bladder cancer is a common human malignancy. Conventional ultrasound and white-light cystoscopy are often used for bladder cancer diagnosis and resection, but insufficient specificity results in a high bladder cancer recurrence rate. New strategies for the diagnosis and resection of bladder cancer are needed. In this study, we developed a highly specific peptide-based probe for bladder cancer photoacoustic imaging (PAI) diagnosis and near-infrared (NIR)-imaging-guided resection after instillation. A bladder cancer-specific peptide (PLSWT7) was selected by in vivo phage-display technology and labeled with IRDye800CW to synthesize a bladder cancer-specific dual-modality imaging (DMI) probe (PLSWT7-DMI). The feasibility of PLSWT7-DMI-based dual-modality PAI-NIR imaging was assessed in vitro, in mouse models, and ex vivo human bladders. An air-pouch bladder cancer (APBC) model suitable for probe instillation was established to evaluate the probe-based bladder cancer PAI diagnosis and NIR-imaging-guided resection. Human bladders were used to assess whether the PLSWT7-DMI-based DMI strategy is a translatable approach for bladder cancer detection and resection. The probe exhibited excellent selectivity and specificity both in vitro and in vivo Postinstillation of the probe, tumors <3 mm were detectable by PAI, and NIR-imaging-guided tumor resection decreased the bladder cancer recurrence rate by 90% and increased the survival in the mouse model. Additionally, ex vivo NIR imaging of human bladders indicated that PLSWT7-DMI-based imaging would potentially allow precise resection of bladder cancer in clinical settings. This PLSWT7-DMI-based DMI strategy was a translatable approach for bladder cancer diagnosis and resection and could potentially lower the bladder cancer recurrence rate. Mol Cancer Ther; 17(10); 2100-11. ©2018 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Metabolome
  • Metabolomics / methods
  • Mice
  • Molecular Imaging* / methods
  • Peptide Library
  • Peptides / metabolism*
  • Spectroscopy, Near-Infrared
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / surgery

Substances

  • Biomarkers, Tumor
  • Peptide Library
  • Peptides