MRI analysis of hydrogel-loaded apatinib for local therapy of hepatocellular carcinoma model in nude mice.

ABSTRACT

AIM: To investigate the effect of local treatment of gadolinium-polyethylene glycol (Gd-PEG) hydrogel containing apatinib injected into hepatocellular carcinoma model of HepG2 in nude mice, and to evaluate the MRI findings in vivo. METHODS: HepG2 cells were treated in vitro and OD 450 value were measured. The four groups (n = 6) were Apatinib-Gd-PEG hydrogel, Gd-PEG hydrogel, Apatinib, and Saline. T1WI and DWI scans were performed before and 1d, 3d, and 14d postoperatively. The samples were examined by histomorphology and immunohistochemistry for CD34 and VEGFR2. Microvessel density (MVD) was evaluated and the average optical density (AOD) of VEGFR2 was obtained by IPP6.0 image software. RESULTS: The OD450-time curves of Gd-PEG hydrogel and phosphate buffer saline (PBS) were similar and that of apatinib at all concentrations are located below; the higher the concentration, the lower the curve. On T1WI and DWI, the newly injected Gd-PEG hydrogel showed significant high signal and was immobilized in the tumor. Subsequently, the size and signal of Gd-PEG hydrogel gradually decreased with time. In Apatinib-Gd-PEG hydrogel group, compared with other three groups, MRI and histomorphology showed that the necrotic area of hepatocellular carcinoma model was larger, immunohistochemistry displayed minimal expression of CD34 and VEGFR2, the AOD of VEGFR2 and MVD differed markedly. CONCLUSION: Gd-PEG hydrogel can significantly enhance and prolong the inhibitory effect of apatinib. It can be visualized by MRI, which can be used to evaluate the local therapeutic effect.