Journal
TALANTA
Volume 255, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.talanta.2022.124225
Keywords
Pancreatic adenocarcinoma; Peptide; PDGFR?; Surface plasmon resonance; Fluorescence-guided surgery; SPECT-CT
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The 5-year survival rate for pancreatic adenocarcinoma (PA) is less than 10%, but early-stage diagnosis and resection can increase the 4-year survival rate up to 78%. A novel PDGFR beta-targeting peptide (YQGX-10) was designed and coupled with a near-infrared fluorescent dye for precise detection of PA. The probe showed high affinity and specificity and could be used for NIRF-guided tumor resection of PA. A radioactive probe was also constructed for the diagnosis of PA with high specificity and sensitivity.
The 5-year survival rate for pancreatic adenocarcinoma (PA) is less than 10%, making it one of the most lethal forms of cancer. Early-stage diagnosis and resection of the incipient lesions could increase the 4-year survival rate of PA up to 78%. Platelet-derived growth factor receptor beta (PDGFR beta), an oncogenic key regulator for migration, proliferation and angiogenesis of cancer cells, has been proved to be aberrantly expressed in the majority of PA. Herein, by amino acid substitution strategy and surface plasmon resonance (SPR) analysis, we designed a novel PDGFR beta-targeting peptide (YQGX-10) with high affinity (Kd = 227.7 nM) and coupled it with a near-infrared fluorescent (NIRF) dye MPA for precisely detection of PA. Great binding affinity and specificity were displayed in a series of in vitro assays. NIRF imaging experiments demonstrated that the synthesized probe could be highly accumulated in xenograft and orthotopic BxPC-3 tumors and provide favorable tumor contrast in the mice, offering a potential novel approach for the early diagnosis of PA. Moreover, YQGX-10 could visualize tumor boundaries and minor lesions in BxPC-3 xenograft mice, shedding a new light on NIRF-guided tumor resection of PA. In addition, we successfully constructed the radioactive probe 99mTc-HYNIC-YQGX-10 for the diagnosis of PA with high specificity and sensitivity. In summary, the probe warrants further exploration for clinical translation in the early diagnosis and NIRF-guided surgery of PA.
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