APT imaging of hepatocellular carcinoma signals an effective therapeutic response in advance of tumor shrinkage
Creators: name: Wang, Xiaojing
name: Ishimatsu, Keisuke
name: Li, Junjie
name: Wen, Xiaodong
name: Ou, Weijun
name: Anwar, Arnida
name: Chaudhary, Jaideep
name: Takahashi, Masaya
name: Sherry, A Dean
name: Corbin, Ian R
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biophysics
subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Cancer

description: <b>Aim:</b> The aim of this study was to assess the utility of weighted amide proton transfer (APT<sub>w</sub>) MRI in three different rodent models of hepatocellular carcinoma (HCC). <b>Methods:</b> APT<sub>w</sub> MRI was evaluated in models of diethylnitrosamine (DEN) induced HCC, N1S1 syngeneic orthotopic xenograft and human HepG2 ectopic xenograft. <b>Results:</b> All models of HCC showed a higher APT<sub>w</sub> signal over the surrounding normal tissues. In the DEN model, the APT<sub>w</sub> signal could differentiate HCC lesions from benign nodules. Intra-arterial administration of low-density lipoprotein docosahexaenoic acid (LDL-DHA) nanoparticles to N1S1 xenografts rapidly lowered the tumor APT<sub>w</sub> signal within 72 h. Direct injections of LDL-DHA nanoparticles into HepG2 xenografts also showed similar therapeutic responses. <b>Conclusion:</b> We have demonstrated the utility of APT<sub>w</sub> imaging in the diagnostic/therapeutic management of HCC. The aim of this study was to evaluate a specific imaging method called amide proton transfer (APT) MRI in different animal models of primary liver cancer. Three models of liver cancer were developed by chemical induction (in rat) and transplantation of rat and human tumor cells in rat and mouse respectively. A higher APT<sub>w</sub> signal was detected in all tumor models of liver cancer. In the chemical induction model, APT<sub>w</sub> MRI could even distinguish between cancer and benign growths in the liver. Treatments with anticancer nanomedicines rapidly decreased tumor APT<sub>w</sub> signals which was accompanied with significant tumor cell death. These findings demonstrated that APT<sub>w</sub> imaging is a useful tool in the management of liver cancer. This study examined the utility of APT MRI in three animal models of liver cancer. Data revealed that APT<sub>w</sub> MRI can identify liver tumors from normal liver and can detect tumor killing following drug treatment. ATP MRI may be a useful tool for managing subjects with liver cancer. The MRI APT<sub>w</sub> signal is an innovative molecular imaging biomarker that is significantly enhanced in malignant tissues relative to normal tissues. Three preclinical animal models of HCC where employed in this study to evaluate the utility of APT<sub>w</sub> imaging in HCC. Chemical induced HCC (DEN), syngeneic orthotopic xenograft (N1S1 hepatoma) and ectopic human xenografts (HepG2) all displayed and increased APT<sub>w</sub> signal over their surrounding normal tissues. APT<sub>w</sub> imaging was able to differentiate HCC lesions from dysplastic/regenerative nodules. Intra-arterial locoregional administration of LDL-DHA nanoparticles to N1S1 orthotopic xenografts selectively showed a progressive decrease in tumor APT<sub>w</sub> signal over 72 h post injection. The loss of APT<sub>w</sub> signal in the N1S1 tumor correlated with treatment induced tumor necrosis. Direct injections of LDL-DHA nanoparticles into ectopic human HepG2 xenografts similarly showed depletion of the tumor APT<sub>w</sub> signal and pronounced tumor destruction. APT<sub>w</sub> imaging proved to be highly sensitive to LDL-DHA mediated treatment of HCC. APT<sub>w</sub> imaging may prove to be a valuable tool in the diagnostic and therapeutic management of HCC.