Predicting Therapeutic Efficacy of Vascular Disrupting Agent CA4P in Rats with Liver Tumors by Hepatobiliary Contrast Agent Mn-DPDP-Enhanced MRI

Yewei Liu; Qiu Guan; Xiangyong Kong; Frederik De Keyzer; Yuanbo Feng; Feng Chen; Jie Yu; Jianjun Liu; Shaoli Song; Jos van Pelt; Johan Swinnen; Guy Bormans; Raymond Oyen; Shuncong Wang; Gang Huang; Yicheng Ni; Yue Li

Translational Oncology (Jan 2020)

Predicting Therapeutic Efficacy of Vascular Disrupting Agent CA4P in Rats with Liver Tumors by Hepatobiliary Contrast Agent Mn-DPDP-Enhanced MRI

Yewei Liu,
Qiu Guan,
Xiangyong Kong,
Frederik De Keyzer,
Yuanbo Feng,
Feng Chen,
Jie Yu,
Jianjun Liu,
Shaoli Song,
Jos van Pelt,
Johan Swinnen,
Guy Bormans,
Raymond Oyen,
Shuncong Wang,
Gang Huang,
Yicheng Ni,
Yue Li

Affiliations

Yewei Liu: Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China; Biomedical Group, Campus Gasthuisberg, KU Leuven, Leuven 3000, Belgium; Institute of Clinical Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China
Qiu Guan: College of Computer Science, Zhejiang University of Technology, Hangzhou 310027, China
Xiangyong Kong: College of Computer Science, Zhejiang University of Technology, Hangzhou 310027, China
Frederik De Keyzer: Biomedical Group, Campus Gasthuisberg, KU Leuven, Leuven 3000, Belgium
Yuanbo Feng: Biomedical Group, Campus Gasthuisberg, KU Leuven, Leuven 3000, Belgium
Feng Chen: Biomedical Group, Campus Gasthuisberg, KU Leuven, Leuven 3000, Belgium
Jie Yu: Biomedical Group, Campus Gasthuisberg, KU Leuven, Leuven 3000, Belgium
Jianjun Liu: Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China; Institute of Clinical Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Shaoli Song: Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China; Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China
Jos van Pelt: Biomedical Group, Campus Gasthuisberg, KU Leuven, Leuven 3000, Belgium
Johan Swinnen: Biomedical Group, Campus Gasthuisberg, KU Leuven, Leuven 3000, Belgium
Guy Bormans: Biomedical Group, Campus Gasthuisberg, KU Leuven, Leuven 3000, Belgium
Raymond Oyen: Biomedical Group, Campus Gasthuisberg, KU Leuven, Leuven 3000, Belgium
Shuncong Wang: Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China; Biomedical Group, Campus Gasthuisberg, KU Leuven, Leuven 3000, Belgium
Gang Huang: Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China; Institute of Clinical Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China; Gang Huang, MD, PhD, Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China
Yicheng Ni: Biomedical Group, Campus Gasthuisberg, KU Leuven, Leuven 3000, Belgium; Yicheng Ni, MD, PhD, Theragnostic Laboratory, Department of Imaging and Pathology, Biomedical Group, KU Leuven, Herestraat 49, Leuven 3000, Belgium
Yue Li: Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China; Biomedical Group, Campus Gasthuisberg, KU Leuven, Leuven 3000, Belgium; Address all correspondence to: Yue Li, PhD, Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.

Journal volume & issue: Vol. 13, no. 1
pp. 92 – 101

Abstract

Read online

To evaluate hepatobiliary-specific contrast agent (CA) mangafodipir trisodium (Mn-DPDP)–enhanced magnetic resonance imaging (MRI) for predicting the therapeutic efficacy of the vascular disrupting agent combretastatin A4 phosphate (CA4P) in rats with primary and secondary liver tumors, 36 primary hepatocellular carcinomas (HCCs) were raised by diethylnitrosamine gavage in 16 male rats, in 6 of which one rhabdomyosarcomas (R1) was intrahepatically implanted as secondary liver tumors. On a 3.0T MR scanner with a wrist coil, tumors were monitored weekly by T2-/T1-weighted images (T2WI/T1WI) and characterized by Mn-DPDP-enhanced MRI. CA4P-induced intratumoral necrosis was depicted by nonspecific gadoterate meglumine (Gd-DOTA)–enhanced MRI before and 12 h after therapy. Changes of tumor-to-liver contrast (ΔT/L) on Mn-DPDP-enhanced images were analyzed. In vivo MRI findings were verified by postmortem microangiography and histopathology. Rat models of primary HCCs in a full spectrum of differentiation and secondary R1 liver tumors were successfully generated. Mn-DPDP-enhanced ΔT/L was negatively correlated with HCC differentiation grade (P < 0.01). After treatment with CA4P, more extensive tumoral necrosis was found in highly differentiated HCCs than that in moderately and poorly differentiated ones (P < 0.01); nearly complete necrosis was induced in secondary liver tumors. Mn-DPDP-enhanced MRI may help in imaging diagnosis of primary and secondary liver malignancies of different cellular differentiations and further in predicting CA4P therapeutic efficacy in primary HCCs and intrahepatic metastases.

Published in Translational Oncology

ISSN: 1944-7124 (Print); 1936-5233 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/translational-oncology/

About the journal