Comparison of 2beta-carbomethoxy-3beta-(4-[18F]fluorophenyl)tropane and N-(3-[18F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane, tracers for imaging dopamine transporter in rat.
OBJECTIVE
This study compares 2beta-carbomethoxy-3beta-(4-[(18)F]fluorophenyl)tropane ([(18)F]beta-CFT) and N-(3-[(18)F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane ([(18)F]beta-CFT-FP) as radiotracers for imaging the dopamine transporter (DAT) in rat.


METHODS
Biodistribution, specificity and selectivity of the radiotracers were studied ex vivo in rats pre-treated with specific antagonists for DAT, serotonin transporter (SERT) and noradrenalin transporter (NET) and in control rats. Positron emission tomography (PET) studies were performed using an HRRT scanner. Radiolabelled metabolites were analyzed with thin-layer chromatography.


RESULTS
[(18)F]beta-CFT showed slow kinetics with a maximum striatum/cerebellum uptake ratio of 9.2 at 120 min. [(18)F]beta-CFT-FP showed fast kinetics with a maximum ratio of 3.1 at 5 min. Both tracers bound to DAT. [(18)F]beta-CFT also bound to NET. [(18)F]beta-CFT was more resistant to metabolism than [(18)F]beta-CFT-FP.


CONCLUSIONS
Structural modifications of [(18)F]beta-CFT significantly changed its biological properties, as shown by [(18)F]beta-CFT-FP. [(18)F]beta-CFT is a suitable tracer for both preclinical and human PET studies, but [(18)F]beta-CFT-FP is less suitable as a PET tracer.
Marjamäki
Päivi
P
MediCity/PET Preclinical Laboratory, Turku PET Centre, University of Turku, Tykistökatu 6A, FI-20520, Turku, Finland. paivi.marjamaki@utu.fi
Haaparanta
Merja
M
Forsback
Sarita
S
Fagerholm
Veronica
V
Eskola
Olli
O
Grönroos
Tove
T
Koivula
Teija
T
Solin
Olof
O
D000818:Animals; D001921:Brain / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D009662:Nortropanes / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution; D014326:Tropanes / Q000737:chemistry / Q000493:pharmacokinetics
C552177:2beta-carbomethoxy-3beta-(4-(18F)fluorophenyl)tropane; D050483:Dopamine Plasma Membrane Transport Proteins; C552178:N-(3-(18F)fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane; D009662:Nortropanes; D011849:Radioactive Tracers; D014326:Tropanes