In Vivo Anchoring Bis‐Pyrene Probe for Molecular Imaging of Early Gastric Cancer by Endoscopic Techniques

Abstract

With the development of blue laser endoscopy (BLE) technique, it's often used to diagnose early gastric cancer (EGC) by the morphological changes of blood vessels through BLE. However, EGC is still not obvious to identify, resulting in a high rate of missed diagnosis. Molecular imaging can show the changes in early tumors at molecular level, which provides a possibility for diagnosing EGC. Therefore, developing a probe that visually monitors blood vessels of EGC under BLE is particularly necessary. Herein, a bis-pyrene (BP) based nanoprobe (BP-FFVLK-(PEG)-RGD, M 1 ) is designed, which can target angiogenesis and self-assemble into fibers in situ, resulting in stable and long-term retention in tumor. Moreover, M 1 probe can emit yellow-green fluorescence for imaging under BLE. M 1 probe is confirmed to steadily remain in tumor for up to 96 hours in mice transplanted subcutaneously. In addition, the M 1 probe is able to target angiogenesis for molecular imaging of isolated human gastric cancer tissue under BLE. Finally, M 1 probe i.v. injected into primary gastric cancer model rabbits successfully highlighted the tumor site under BLE, which is confirmed by pathological analysis. It's the first time to develop a probe for diagnosing EGC by visualizing angiogenesis under BLE, showing great clinical significance.

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“…P(3HB-co-4HB) characterization: Nuclear magnetic resonance ( 1 H NMR) spectra were analyzed on Agilent DD2 at 600 MHz with chloroformd as solvent. [47] Fourier transform infrared (FTIR) spectra were analyzed in the range of 450 to 4000 cm −1 on a Perkin-Elmer FTIR spectrometer (Spectrum TWO, PerkinElmer). [48] Gel permeation chromatography was analyzed on a Waters 1515 instrument (Waters, U.S.A) equipped with a guard column MIXED 7.5 × 50 mm PL column and two MIXED-C 7.5 × 300 mm columns and a differential refractive index detector.…”

“…Nuclear magnetic resonance ( 1 H NMR) spectra were analyzed on Agilent DD2 at 600 MHz with chloroform‐d as solvent. [ 47 ]…”

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“…The system demonstrated similar levels of sensitivity and specificity compared with all levels of endoscopists, reporting a positive predictive value of 91.3% and negative predictive value of 93.8% [ 7 ]. Luo et al created a Gastrointestinal Artificial Intelligence Diagnostic System (GRAIDS), a system that may assist nonexpert endoscopists in diagnosing upper GI cancers at a level comparable to specialists [ 8 ]. Image-enhanced endoscopy (IEE) employs narrow-band spectrum or blue laser imaging to amplify the micro-vessel patterns and color disparities of the stomach mucosa and structural characteristics [ 9 ].…”

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“…Pyrene, as a star luminescent molecule, has been widely used in various fields, such as organic light-emitting diodes (OLEDs), [1][2][3] fluorescent biological probes, [4][5][6][7] chemosensors [8][9][10] and photocatalysts [11][12][13][14] due to its simple chemical structure and excellent fluorescence properties. However, the use of pyrene as a solid-state luminescent material still faces many serious challenges.…”