Fibronectin-Targeting Dual-Modal MR/NIRF Imaging Contrast Agents for Diagnosis of Gastric Cancer and Peritoneal Metastasis

The prevalence and fatality rates of gastric cancer (GC) remain elevated, with advanced stages presenting a grim prognosis. Noninvasive diagnosis of GC cancer often proves challenging until the disease has progressed to an advanced stage or metastasized. Initially, the level of fibronectin (FN) in c...

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Bibliographic Details
Published in:Bioconjugate chemistry 2024-06, Vol.35 (6), p.843-854
Main Authors: Yang, Ningxin, Huang, Yuelin, Wang, Xiaoyu, Wang, Dengbin, Yao, Defan, Ren, Gang
Format: Article
Language:English
Subjects:
Animals
Cancer
Cell Line, Tumor
Contrast agents
Contrast media
Contrast Media - chemistry
Diagnosis
Fibroblasts
Fibronectin
Fibronectins - metabolism
Gadolinium
Gastric cancer
Heterocyclic Compounds
Humans
Magnetic resonance imaging
Magnetic Resonance Imaging - methods
Medical imaging
Metastases
Metastasis
Mice
Optical Imaging - methods
Organometallic Compounds - chemistry
Peritoneal Neoplasms - diagnosis
Peritoneal Neoplasms - diagnostic imaging
Peritoneal Neoplasms - secondary
Peritoneum
Probes
Signal to noise ratio
Stomach Neoplasms - diagnosis
Stomach Neoplasms - diagnostic imaging
Stomach Neoplasms - pathology
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Summary:The prevalence and fatality rates of gastric cancer (GC) remain elevated, with advanced stages presenting a grim prognosis. Noninvasive diagnosis of GC cancer often proves challenging until the disease has progressed to an advanced stage or metastasized. Initially, the level of fibronectin (FN) in cancer-associated fibroblasts (CAFs) of GC was at least 3.7 times higher than that in normal fibroblasts. Herein, two FN-targeting magnetic resonance/near-infrared fluorescence (MR/NIRF) imaging contrast agents were developed to detect GC and peritoneal metastasis noninvasively. The probes CREKA-Cy7-(Gd-DOTA) and CREKA-Cy7-(Gd-DOTA)3 demonstrated significant FN-targeting capability (with dissociation constants of 1.0 and 2.1 mM) and effective MR imaging performance (with proton relaxivity values of 9.66 and 27.44 mM–1 s–1 at 9.4 T, 37 °C). In vivo imaging revealed a high signal-to-noise ratio and successful visualization of GC metastasis using NIRF imaging as well as successful tumor detection in MR imaging. Therefore, this study highlights the potential of FN-targeting probes for GC diagnosis and aids in the advancement of new diagnostic strategies for the clinical detection of GC.
ISSN:1043-1802
1520-4812
1520-4812
DOI:10.1021/acs.bioconjchem.4c00208