Effects of antiangiogenic drugs on FDG, FLT and methionine uptake in LS180 and HUVEC

Objectives Angiogenesis is an attractive target for tumor therapy because angiogenesis has an essential role for tumor growth and metastasis. Various types of antiangiogenic drugs have been developed and evaluated in a clinical setting. We evaluated the effects of antiangiogenic drugs on uptake of ³H-2-Deoxy-D-glucose (DG), ³H-3’-Fluorodeoxythymidine (FLT) and ¹⁴C-methionine (MET).

Methods Thalidomide (TNF-α and VEGF production inhibitor), 2-methoxyestradiol (2-ME; microtubule inhibitor) and SU5416 (Flk-1/KDR receptor tyrosine kinase inhibitor) were used as antiangiogenic drugs. Effects of antiangiogenic drugs (0.1, 1 and 10 μM) on cell growth of human colon cancer (LS180) and human umbilical vein endothelial cells (HUVEC) were evaluated. Apoptosis induced by antiangiogenic drugs was detected using Cell Death Detection ELISA Plus. After antiangiogenic drugs were incubated with LS180 and HUVEC for 24 h, respectively, DG, FLT and MET uptake in LS180 and HUVEC were measured. Effect of 2-ME on tumor uptake of ¹⁸F-FDG and FLT was investigated in LS180 tumor bearing mice.

Results -ME dose-dependently inhibited the growth of LS180 and HUVEC. SU5416 inhibited only the growth of HUVEC. Thalidomide did not show the inhibition effect on the growth of LS180 and HUVEC. In addition, 2-ME and SU5416 induced apoptosis in LS180 and HUVEC. FLT uptake, but not DG and MET, in LS180 was decreased by 2-ME (10 µM). DG, FLT and MET uptake in HUVEC were suppressed by 2- ME and SU5416 in a dose-dependent manner. In tumor bearing mice, tumor uptake of FLT, but not ¹⁸F-FDG, was decreased by 2-ME, while growth rate in treatment group (1.7 times) was almost same as that in control group (2.0 times) at 3 days after treatment.

Conclusions These results show that ¹⁸F-FLT would be a good radiopharmaceutical for early detection of the antiangiogenic effects