2-Methoxyestradiol (1) is an endogenous metabolite of estradiol that has been shown to inhibit cell proliferation and angiogenesis. In this study, 2-[methyl-(11)C]methoxyestradiol ([(11)C]1) was synthesized and evaluated for in vivo studies on angiogenesis. Radiotracer [(11)C]1 was synthesized at a decay-corrected radiochemical yield of 25-34% from [(11)C]CH(3)I with a specific activity of 34-38 GBq/micromol. In vitro human umbilical vein endothelial cell uptake studies demonstrated that [(11)C]1 uptake increased time-dependently and that this uptake was inhibited by 70% in the presence of Compound 1, indicating its specific binding to cells. Tissue distribution in mice implanted with Lewis lung carcinoma cells showed high radioactivity accumulation in the liver, lungs and kidneys, and a tumor-to-muscle uptake ratio of 2.36. Pharmacokinetic analysis in mice intravenously injected with [(11)C]1 demonstrated a t(1/2)alpha of 0.36 min, a t(1/2)beta of 19 min, a clearance of 0.36 ml/min and a volume of distribution of 52.9 ml. In addition, Compound 1 showed linear pharmacokinetics at dose levels between 0.14 and 8.5 microg in mice. Taken together, [(11)C]1 may be useful for in vivo studies on angiogenesis.