Issue 20, 2021

c-Met-targeted near-infrared fluorescent probe for real-time depiction and dissection of perineural invasion and lymph node metastasis lesions in pancreatic ductal adenocarcinoma xenograft models

Abstract

Pancreatic ductal adenocarcinoma (PDAC), a fatal malignant tumour, has a high postoperative recurrence rate, mainly due to the difficulty of discerning occult lesions, including those related to perineural invasion (PNI) and lymph node metastasis (LNM). Cellular mesenchymal-epithelial transition factor (c-Met), an excellent imaging marker, is aberrantly expressed in the majority of PDACs. Thus, we plan to utilize a c-Met-targeted near-infrared fluorescent (NIRF) probe for real-time visualization and dissection of PDAC, and corresponding PNI and LNM lesions. Immunohistochemistry showed c-Met expression in PDAC, PNI and LNM reached 94.3% (100/106), 88.3% (53/60), and 71.4% (25/35), respectively, and its expression in PNI and LNM was significantly correlated with that in primary PDAC (r = 0.66, p < 0.0001 and r = 0.44, p < 0.01, respectively). SHRmAb-IR800 was successfully synthesized using an anti-c-Met antibody and a NIRF dye. The in vitro targeting ability of SHRmAb-IR800 was higher in CFPAC1 cells (c-Met positive) than in Miapaca-2 cells (c-Met negative) (p < 0.05). In vivo NIRF imaging of CFPAC1 subcutaneous tumours demonstrated higher accumulation of SHRmAb-IR800 than the control probe (p < 0.05). The signal-to-background ratio (TBR) of an orthotopic PDAC tumour was 3.38 ± 0.46, and imaging with SHRmAb-IR800 facilitated the resection of metastatic lesions with sensitivity and specificity values of 93.3% (56/60) and 87.1% (27/31), respectively. Furthermore, tiny PNI and LNM lesions in xenograft models were detected by NIRF imaging, with TBRs measuring 2.59 ± 0.19 and 2.88 ± 0.72, respectively. Therefore, the clinical translation of this probe might shed new light on NIRF-guided pancreatectomy and improve the surgical prognosis of PDAC patients.

Graphical abstract: c-Met-targeted near-infrared fluorescent probe for real-time depiction and dissection of perineural invasion and lymph node metastasis lesions in pancreatic ductal adenocarcinoma xenograft models

Supplementary files

Article information

Article type
Paper
Submitted
30 Apr 2021
Accepted
25 Jun 2021
First published
02 Jul 2021

Biomater. Sci., 2021,9, 6737-6752

c-Met-targeted near-infrared fluorescent probe for real-time depiction and dissection of perineural invasion and lymph node metastasis lesions in pancreatic ductal adenocarcinoma xenograft models

D. Li, M. Yang, M. Liang, C. Mei, Y. Lin, F. Yang, Y. Xiao, Y. Chen, F. Wang, J. Mao and Z. Su, Biomater. Sci., 2021, 9, 6737 DOI: 10.1039/D1BM00674F

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