Synthesis and in vivo distribution in the rat of several fluorine-18 labeled N-fluoroalkylaporphines.
A method is described for the rapid production and purification of new potential dopamine agonists. Via microwave heating 10,11-dihydroxy-N-(n-2-fluoroethyl)norapomorphine (FNEA), 10,11-dihydroxy-N-(n-3-fluoropropyl)norapomorphine (FNPA) and 2,10,11-trihydroxy-N-(n-3-fluoropropyl)norapomorphine (FTNPA) and their isotopic fluorine-18 derivatives were synthesized. The fluorine-18 label was introduced via N-fluoroalkylation of acylated noraporphine derivatives with no-carrier-added (n.c.a.) 18FCH2CH2I and 18FCH2CH2CH2I. Within 160 min (E.O.B.), radiochemical yields of 13-29% (corrected for decay) were achieved based on [18F]fluoroalkyliodide. The specific activity obtained, ranged from 15 to 75 GBq/mumol. The fluorine-18 labeled compounds were investigated for their in vivo binding potency to the D2-receptors. After i.v. injection, the distribution was studied in rats. High uptakes of the N-[18F]fluoroalkylaporphines were found in the lungs, liver, adrenals and kidneys. No significant different radioactive accumulation was observed in striatum, cerebellum and frontal cortex. Dopamine depletion with reserpine did not affect the striatum to cerebellum ratio at low dosage of N-[18F]fluoroalkylaporphines (10 nmol/kg).
Zijlstra
S
S
PET Center, GCCS, Groningen, The Netherlands.
Visser
G M
GM
Korf
J
J
Vaalburg
W
W
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D015259:Dopamine Agents; D005462:Fluorine Radioisotopes; C080805:10,11-dihydroxy-N-(n-3-fluoropropyl)norapomorphine; C080806:2,10,11-trihydroxy-N-(n-3-fluoropropyl)norapomorphine; C080804:10,11-dihydroxy-N-(n-2-fluoroethyl)norapomorphine; D001058:Apomorphine