Presentation Authors: Li Peng*, Harbin, China, People's Republic of, Wenting Shang, Jie Tian, Beijing, China, People's Republic of, Wanhai Xu, Harbin, China, People's Republic of
Introduction: Bladder cancer (BC) is a common human malignancy. White light (WL) cystoscopy is the gold standard to detect BC intraoperatively, but up to 30% tumors will be missed, leading to the high recurrence rate of NMIBC. Therefore, we developed a peptide-based probe for NMIBC detection under near-infrared (NIR) imaging to improve the detection of BC using our technique.
Methods: In vivo phage display technology was used to select BC targeting peptide (P7) and the peptide was labeled with NIR fluorescein IRDye800CW to synthesize BC specific probe PLSWT7. BC cell lines and orthotopic BC mice model were used to assess the specificity of PLSWT7 in vitro and in vivo. Then twenty patients diagnosed with nonmuscle invasive BC (NMIBC) were enrolled. Following probe intracvesical administration, the entire mucosa was imaged under WL and NIR imaging via our homemade endoscopy that could switch between the two mode. The illuminated lesions under NIR imaging were biopsied and sent for histopathological examination.
Results: The peptide P7 exhibited the highest selectivity among all the phage clones. After labeled with IRDye800CW, the probe PLSWT7 exhibited excellent specificity in vitro and in vivo. After intravesical administration, the probe specifically bound with NMIBC lesions but not normal mucosa or benign lesions in BC patients. Small papillary tumors and carcinoma in situ (CIS) missed under white light imaging were clearly visualized using PLSWT7-DMI fluorescence endoscopy with 91.2% sensitivity and 90% specificity were. The tumor detection rate of PLSWT7-DMI fluorescence endoscopy was 79.4% versus 92.6% for white light imaging.
Conclusions: We developed a phage display-derived, highly specific probe for BC detection under NIR imaging. Probe-based NIR imaging allows the visualization of the missed tumors under WL imaging, thereby improves BC detection rate. This approach holds great potential for clinical translation.
Source of Funding: National Natural Science Foundation of China under Grant Nos. 81270022