Phage Display-Derived Peptide-Based Dual-Modality Imaging Probe for Bladder Cancer Diagnosis and Resection Postinstillation: A Preclinical Study.
2018
Bladder cancer (BC) is a common human malignancy. Conventional ultrasound and
white light cystoscopy are often used for BC diagnosis and resection, but insufficient
specificity results in a high BC recurrence rate. New strategy for the diagnosis and
resection of BC are needed. In this study, we developed a highly specific
peptide-based probe for BC photoacoustic imaging (PAI) diagnosis and near-infrared
(NIR)-imaging-guided resection post-instillation. A BC-specific peptide (PLSWT7)
was selected by in vivo phage display technology and labeled with IRDye800CW to
synthesize a BC-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 BC (APBC) model
suitable for probe instillation was established to evaluate the probe-based BC PAI
diagnosis and NIR-imaging-guided resection. Human bladders were used to assess
whether PLSWT7-DMI-based DMI strategy is a translatable approach for BC
detection and resection. The probe exhibited excellent selectivity and specificity both in vitro and in vivo . Post-instillation of the probe, tumors
PAI, and NIR-imaging-guided tumor resection decreased the BC 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 allowed precise resection of BC in clinical settings. This
PLSWT7-DMI-based DMI strategy was a translatable approach for BC diagnosis and
resection and could potentially lower the BC recurrence rate.
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