Synthesis and in vivo distribution in the rat of several fluorine-18 labeled 5-hydroxy-2-aminotetralin derivatives.
A method is described for the rapid production and purification of new potential dopamine agonists. Via thermal heating (refluxing in an oil bath) and microwave exposure 2-[N-n-3-fluoropropyl-N-(4-methylphenyl)ethylamino]-5-hydroxyte tralin (12), 2-[N-n-3-fluoropropyl-N-(4-fluorophenyl)ethylamino]-5-hydroxyte tralin (13), and their isotopic fluorine-18 derivatives were synthesized, respectively. The fluorine-18 label was introduced via N-fluoroalkylation with no-carrier-added (n.c.a.) 18FCH2CH2CH2I. In 115 min, radiochemical yields of 11% (corrected for decay) were achieved for both compounds. The specific activity ranged from 15-75 GBq/mumol. After i.v. injection in rats, the fluorine-18 labeled compounds were evaluated for their in vivo binding to the D2-receptors. The radioactivity levels in the striatum, nucleus accumbens and tuberculum olfactorius were not significantly higher than in the cerebellum and frontal cortex at 15, 30 and 60 min after administration of the tetralin derivatives. Dopamine depletion with reserpine did not affect the uptake in the dopamine D2-receptor rich area. Remarkable high uptakes were found in the adrenal for both compounds.
Zijlstra
S
S
PET Center, University of Groningen, The Netherlands.
Elsinga
P H
PH
Oosterhuis
E Z
EZ
Visser
G M
GM
Korf
J
J
Vaalburg
W
W
D000818:Animals; D005462:Fluorine Radioisotopes; D007275:Injections, Intravenous; D007553:Isotope Labeling; D008297:Male; D010627:Phenethylamines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D010627:Phenethylamines; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; C080752:2-(N-n-3-fluoropropyl-N-(4-methylphenyl)ethylamino)-5-hydroxytetralin; C080753:2-(N-n-3-fluoropropyl-N-(4-fluorophenyl)ethylamino)-5-hydroxytetralin