TY - JOUR
T1 - Ex vivo evaluation of N-(3-[18F]fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)nortropane in rats
AU - Koivula, Teija
AU - Marjamäki, Päivi
AU - Haaparanta, Merja
AU - Fagerholm, Veronica
AU - Grönroos, Tove
AU - Lipponen, Tiina
AU - Perhola, Outi
AU - Vepsäläinen, Jouko
AU - Solin, Olof
PY - 2008/2
Y1 - 2008/2
N2 - 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.
AB - 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.
KW - Animals
KW - Binding, Competitive
KW - Bone and Bones/diagnostic imaging
KW - Cerebellum/diagnostic imaging
KW - Cocaine/analogs & derivatives
KW - Corpus Striatum/diagnostic imaging
KW - Dopamine Plasma Membrane Transport Proteins/antagonists & inhibitors
KW - Dopamine Uptake Inhibitors/pharmacology
KW - Fluorine Radioisotopes/pharmacokinetics
KW - Limbic System/diagnostic imaging
KW - Male
KW - Nortropanes/pharmacokinetics
KW - Piperazines/pharmacology
KW - Radioligand Assay/methods
KW - Radionuclide Imaging
KW - Radiopharmaceuticals/pharmacokinetics
KW - Rats
KW - Rats, Sprague-Dawley
KW - Tissue Distribution
U2 - 10.1016/j.nucmedbio.2007.09.006
DO - 10.1016/j.nucmedbio.2007.09.006
M3 - Article
C2 - 18312827
SN - 0969-8051
VL - 35
SP - 177
EP - 183
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 2
ER -