Identification of In Vivo Activity of Defactinib-Microcrystal on Hepatocellular Carcinoma Cells Using Positron Emission Computed Tomography / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare the microcrystal of defactinib and identify the in vivo activity of defactinib-microcrystal on hepatocellular carcinoma (HCC) cells using PET (positron emission computed tomography) methods. METHODS: The protein level of focal adhesion kinase (FAK) in HCC cell lines was examined by Western blot. The solubilizing solution or microcrystal of defactinib was prepared. MHCC97-H cells, which express highest level of FAK, were injected to nude mice to form the subcutaneous tumor. The solubilizing solution or microcrystal of defactinib was injected into tumor tissues. The clearance curve or anti-tumor efficiency of solubilizing solution or microcrystal of defactinib was identified by LC-MS /MS or PET/CT methods. Mice were injected with 300 μCi(11.1 MBq)18F-FDG and analyzed by PET after 50 min. RESULTS: The solubilizing solution or microcrystal of defactinib was successfully prepared. MHCC97-H expresses highest level of FAK than HCC other cell lines. defactinib slowly released by defactinib-microcrystal. Treatment of defactinib-microcrystal sustainably attenuated the absorbing of 18F-FDG in MHCC97-H cells. CONCLUSION: The solubilizing solution or microcrystal of defactinib is successfully prepared. A method to identify the in vivo activity of FAK inhibitor is also established.