INTRODUCTION: The dopamine transporter (DAT) ligand N-(3-fluoropropyl)-2 beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane (beta-CFT-FP) was labeled with fluorine-18, and its biodistribution was evaluated in rats ex vivo. METHODS: The distribution of 18F radioactivity in the brain and peripheral organs and tissues was determined at several time points 5-120 min after intravenous injection of [18F]beta-CFT-FP. RESULTS: The highest brain uptake of [18F]beta-CFT-FP was localized in the striatum; limbic structures also exhibited high uptake. Low uptake was found in the cerebellum. The highest ratio of striatum-to-cerebellum uptake, already reached within 5 min, was 3.1. Pretreatment with the selective DAT inhibitor GBR12909 significantly decreased [18F]beta-CFT-FP uptake in the striatum. In most peripheral tissues, the highest uptake was found at 5 min, indicating fast washout of the radioligand. Some accumulation of (18)F radioactivity was seen in bone as a function of time, reflecting defluorination of the radioligand. CONCLUSION: The results indicate that [18F]beta-CFT-FP is a potential radioligand for studying DAT in vivo with positron emission tomography.
INTRODUCTION: The dopamine transporter (DAT) ligand N-(3-fluoropropyl)-2 beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane (beta-CFT-FP) was labeled with fluorine-18, and its biodistribution was evaluated in rats ex vivo. METHODS: The distribution of 18F radioactivity in the brain and peripheral organs and tissues was determined at several time points 5-120 min after intravenous injection of [18F]beta-CFT-FP. RESULTS: The highest brain uptake of [18F]beta-CFT-FP was localized in the striatum; limbic structures also exhibited high uptake. Low uptake was found in the cerebellum. The highest ratio of striatum-to-cerebellum uptake, already reached within 5 min, was 3.1. Pretreatment with the selective DAT inhibitor GBR12909 significantly decreased [18F]beta-CFT-FP uptake in the striatum. In most peripheral tissues, the highest uptake was found at 5 min, indicating fast washout of the radioligand. Some accumulation of (18)F radioactivity was seen in bone as a function of time, reflecting defluorination of the radioligand. CONCLUSION: The results indicate that [18F]beta-CFT-FP is a potential radioligand for studying DAT in vivo with positron emission tomography.
Authors: Jeffrey S Stehouwer; Lauryn M Daniel; Ping Chen; Ronald J Voll; Larry Williams; Susan J Plott; John R Votaw; Michael J Owens; Leonard Howell; Mark M Goodman Journal: J Med Chem Date: 2010-08-12 Impact factor: 7.446