18F-FLT PET/CT imaging for early monitoring response to CDK4/6 inhibitor therapy in triple negative breast cancer.

Abstract

Our study was to investigate 18F-FLT PET/CT imaging monitor the early response of CDK4/6 inhibitor therapy in triple negative breast cancer (TNBC). MDA-MB-231 and MDA-MB-468 cell lines and corresponding subcutaneous tumor models in CB17-SCID mice were used. Cell viability assay, cell-cycle analysis, and western blotting were performed in vitro experiments. 18F-FLT PET/CT imaging was performed and the value of tumor/muscle (T/M) of mice was measured before and 1-3days after treatment in vivo experiments. Then, the tumor volume was recorded every day for 15days. In the presence of Palbociclib (CDK4/6 inhibitor), the results of in vitro experiments showed that protein pRB and E2F levels were significantly down-regulated in MDA-MB-231 cells leading to G0/G1 arrest with consumption in S phase compared with MDA-MB-468 cells. In PET/CT imaging, the 18F-FLT T/M ratio of treatment group was a significant and sustained reduction from 1 to 3days (all p < 0.05) compared with control group in MDA-MB-231 section. However, there was no significant difference between treatment and control groups in MDA-MB-468 section. Compared with the control group, the tumor volume of the treatment group was significantly reduced from the 11th day in MDA-MB-231 section, but not in MDA-MB-468 section until 15days. 18F-FLT PET/CT imaging can immediately and effectively monitor the early treatment response of CDK4/6 inhibitors in TNBC.