Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Shanghai University of Sport, Shanghai 200438, China.
Bioconjug Chem. 2024 Jun 19;35(6):843-854. doi: 10.1021/acs.bioconjchem.4c00208. Epub 2024 May 22.
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) 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 s 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.
胃癌（GC）的患病率和死亡率仍然居高不下，晚期阶段的预后较差。在疾病进展到晚期或转移之前，GC 癌症的无创诊断通常具有挑战性。最初，GC 癌相关成纤维细胞（CAFs）中的纤连蛋白（FN）水平至少比正常成纤维细胞高 3.7 倍。在此，开发了两种针对 FN 的磁共振/近红外荧光（MR/NIRF）成像对比剂来无创检测 GC 和腹膜转移。探针 CREKA-Cy7-（Gd-DOTA）和 CREKA-Cy7-（Gd-DOTA）表现出显著的 FN 靶向能力（解离常数分别为 1.0 和 2.1 mM）和有效的 MR 成像性能（在 9.4 T、37°C 时质子弛豫率分别为 9.66 和 27.44 mM s）。体内成像显示出高信噪比，并成功使用 NIRF 成像可视化 GC 转移，以及成功在 MR 成像中检测肿瘤。因此，这项研究强调了针对 FN 的探针在 GC 诊断中的潜力，并有助于为 GC 的临床检测推进新的诊断策略。
