β-adrenoceptor can influence the 18F-FDG PET imaging of breast cancer through its regulation to the posttranscriptional level of hexokinase-2

Objectives To investigate the regulation effect of the β-adrenoceptor (ADRB) activity to the levels of GLUT-1 and HK-2, which are related to the glucose uptake, and clarify its influence on the 18F-FDG PET imaging of breast cancer by microPET.

Methods The ADRB1/2 expression of the 4T1 breast cancer cell was tested by western blot (WB) and immunofluorescence. The in vitro drug intervention of ADRB was achieved by adding propranolol or isoproterenol to culture media and the regulation effect of ADRB on GLUT-1 and HK-2 was measured by WB and RT-PCR. The in vivo drug intervention was achieved by intraperitoneally injecting PBS, propranolol or isoproterenol respectively to three groups (n=6) of balb/c mice bearing 4T1 breast cancer. 18F-FDG was injected 1h later and the microPET/CT imaging was done 1h after the 18F-FDG injection. The VOIs of the tumor and the liver reference were drawn, and the T/NT value was calculated. The GLUT-1 and HK-2 in the tumors were detected by immunochemistry.

Results An abundant expression of ARDB1/2 in 4T1 breast cancer cells was identified. The in vitro study suggested that the ADRB activity was positively correlated to the expression level of HK-2 while the real-time PCR indicated that the ARDB had no significant influence to the transcriptional level of HK-2. The analysis on the in vivo imaging indicated a significantly decrease on the T/NT value of the 18F-FDG PET imaging in the propranolol treated group (p= 0.01) and a higher mean T/NT value in the isoproterenol treated group with no significant difference (5.07 vs 4.48, p=0.1783).The immunochemistry testified the in vitro result of the relationship between the pharmacological intervention and the expression levels of GLUT-1 and HK-2.

Conclusions The activity of ARDB is positively correlated to the expression level especially the posttranscriptional level of HK-2 in the 4T1 breast cancer cells. The activity of ARDB can influence the T/NT value of the 18F-FDG PET imaging of the mice bearing 4T1 breast cancer.