Yun Zhang1, Jing Zhao2, Jing Cai2, Jia-Cong Ye2, Yi-Tai Xiao2, Yan Mei2, Mu-Sheng Zeng2, Chuan-Miao Xie3,4, Yong Jiang5, Guo-Kai Feng6. 1. Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Science, Southern Medical University, No.1023 Shatai South Road, Guangzhou, 510515, Guangdong Province, China. 2. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center/Cancer Hospital, 651 Dongfeng East Road, Guangzhou, 510060, China. 3. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center/Cancer Hospital, 651 Dongfeng East Road, Guangzhou, 510060, China. xiechm@sysucc.org.cn. 4. Department of Medical Imaging, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center/Cancer Hospital, 651 Dongfeng East Road, Guangzhou, 510060, China. xiechm@sysucc.org.cn. 5. Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Science, Southern Medical University, No.1023 Shatai South Road, Guangzhou, 510515, Guangdong Province, China. jiang48231@163.com. 6. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center/Cancer Hospital, 651 Dongfeng East Road, Guangzhou, 510060, China. fengguok@sysucc.org.cn.
Abstract
PURPOSE: Magnetic resonance imaging (MRI) has a high spatial resolution for detecting hepatocellular carcinoma (HCC). Integrin α6 has emerged as a diagnostic and prognostic biomarker of HCC. Here, we developed the MR contrast agent RWY-dL-(Gd-DOTA)4 based on the integrin α6-targeted RWY peptide that we previously identified to detect HCC. PROCEDURES: Contrast-enhanced MRI was carried out to evaluate the use of RWY-dL-(Gd-DOTA)4 to detect HCC lesions in subcutaneous and diethylnitrosamine (DEN)-induced HCC mouse models. RESULTS: Enhancement MR signals were observed in HCC-LM3 subcutaneous liver tumors in the first 5 min post-injection of RWY-dL-(Gd-DOTA)4 at a low dose of 0.03 mmol Gd/kg. Moreover, RWY-dL-(Gd-DOTA)4 generated superior contrast enhancement for liver tumors in chemical-induced HCC mice. Importantly, RWY-dL-(Gd-DOTA)4 provided complementary enhancement MR signals to the clinical available hepatobiliary MR contrast agent gadoxetate disodium Gd-EOB-DTPA. Additionally, RWY-dL-(Gd-DOTA)4 showed minimal gadolinium retention in normal tissues and organs at 48 h post-injection. CONCLUSION: These findings potentiate the use of RWY-dL-(Gd-DOTA)4 for the MRI of HCC to improve the diagnosis of HCC.
PURPOSE: Magnetic resonance imaging (MRI) has a high spatial resolution for detecting hepatocellular carcinoma (HCC). Integrin α6 has emerged as a diagnostic and prognostic biomarker of HCC. Here, we developed the MR contrast agent RWY-dL-(Gd-DOTA)4 based on the integrin α6-targeted RWY peptide that we previously identified to detect HCC. PROCEDURES: Contrast-enhanced MRI was carried out to evaluate the use of RWY-dL-(Gd-DOTA)4 to detect HCC lesions in subcutaneous and diethylnitrosamine (DEN)-induced HCCmouse models. RESULTS: Enhancement MR signals were observed in HCC-LM3 subcutaneous liver tumors in the first 5 min post-injection of RWY-dL-(Gd-DOTA)4 at a low dose of 0.03 mmol Gd/kg. Moreover, RWY-dL-(Gd-DOTA)4 generated superior contrast enhancement for liver tumors in chemical-induced HCCmice. Importantly, RWY-dL-(Gd-DOTA)4 provided complementary enhancement MR signals to the clinical available hepatobiliary MR contrast agent gadoxetate disodium Gd-EOB-DTPA. Additionally, RWY-dL-(Gd-DOTA)4 showed minimal gadolinium retention in normal tissues and organs at 48 h post-injection. CONCLUSION: These findings potentiate the use of RWY-dL-(Gd-DOTA)4 for the MRI of HCC to improve the diagnosis of HCC.
Authors: Man-Fung Yuen; Ding-Shinn Chen; Geoffrey M Dusheiko; Harry L A Janssen; Daryl T Y Lau; Stephen A Locarnini; Marion G Peters; Ching-Lung Lai Journal: Nat Rev Dis Primers Date: 2018-06-07 Impact factor: 52.329
Authors: Francesco Bellissimo; Marilia Rita Pinzone; Bruno Cacopardo; Giuseppe Nunnari Journal: World J Gastroenterol Date: 2015-11-14 Impact factor: 5.742
Authors: A Singal; M L Volk; A Waljee; R Salgia; P Higgins; M A M Rogers; J A Marrero Journal: Aliment Pharmacol Ther Date: 2009-04-08 Impact factor: 8.171