Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No.270, Dong'an Road, Xuhui District, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Ann Nucl Med. 2021 May;35(5):600-607. doi: 10.1007/s12149-021-01603-w. Epub 2021 Mar 10.
Our study was to investigate F-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. F-FLT PET/CT imaging was performed and the value of tumor/muscle (T/M) of mice was measured before and 1-3 days after treatment in vivo experiments. Then, the tumor volume was recorded every day for 15 days.
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 F-FLT T/M ratio of treatment group was a significant and sustained reduction from 1 to 3 days (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 15 days.
F-FLT PET/CT imaging can immediately and effectively monitor the early treatment response of CDK4/6 inhibitors in TNBC.
本研究旨在探讨 F-FLT PET/CT 成像监测 CDK4/6 抑制剂在三阴性乳腺癌（TNBC）治疗中的早期反应。
使用 MDA-MB-231 和 MDA-MB-468 细胞系和相应的 CB17-SCID 小鼠皮下肿瘤模型。在体外实验中进行细胞活力测定、细胞周期分析和 Western blot 实验。在体内实验中进行 F-FLT PET/CT 成像，并在治疗前和治疗后 1-3 天测量小鼠的肿瘤/肌肉（T/M）比值。然后，每天记录肿瘤体积 15 天。
在 Palbociclib（CDK4/6 抑制剂）存在的情况下，体外实验结果表明，与 MDA-MB-468 细胞相比，MDA-MB-231 细胞中的蛋白 pRB 和 E2F 水平显著下调，导致 G0/G1 期阻滞，S 期消耗。在 PET/CT 成像中，与对照组相比，治疗组的 F-FLT T/M 比值从第 1 天到第 3 天（均 p<0.05）显著且持续降低，在 MDA-MB-231 组中。然而，在 MDA-MB-468 组中，治疗组与对照组之间无显著差异。与对照组相比，治疗组的肿瘤体积在 MDA-MB-231 组中从第 11 天开始显著减少，但在 MDA-MB-468 组中直到第 15 天才减少。
F-FLT PET/CT 成像可以立即有效地监测 CDK4/6 抑制剂在 TNBC 中的早期治疗反应。
