Dopamine D(4) receptor antagonist 3-(4-[(18)F]fluorobenzyl)-8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one([(18)F]FMTP): radiosynthesis and in vivo characterization in rats.
We synthesized a novel (18)F-labeled dopamine D(4) receptor antagonist (Ki=4.3 nM), 3-(4-[(18)F]fluorobenzyl)-8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one ([(18)F]FMTP), which has exhibited high affinity and selectivity. Radiosyntheses were accomplished by the reaction of fluorine-18-labeled intermediate with 8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one (1) followed by HPLC purification. The overall radiochemical yield of the radiosynthesis was 19.5% (decay corrected), the specific radioactivity was about 110 GBq/micromol and the radiochemical purity was greater than 99%, the time of synthesis and purification was approximately 110 min. Tissue distribution studies of the [(18)F]FMTP in rats showed that the radioactivity in the brain was concentrated in frontal cortex and medulla, the region that has a high density of D(4) receptors. Pre-treatment with nonradioactive FMTP (1.0mg/kg) produced a significant reduction of radioactivity in all the regions. About 40% of total radioactivity in plasma and 100% in rat brain extract represented unchanged radioligand at 60 min after injection as determined by HPLC. These results indicate that [(18)F]FMTP have some specific binding to the D(4) receptor.
Radiopharmaceutical research Center, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, P.O. Box 800-204, Shanghai 201800, P.R. China. haibintian2003@yahoo.com
Tian
T
Hai-Bin
Yin
Y
Duan-Zhi
Zhang
Z
Lan
Wang
W
Li-Hua
Zhang
Z
Chun-Fu
Wang
W
Ming-Wei
Wu
W
Chun-Ying
Li
L
Gu-Cai
Wang
W
Yong-Xian
D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D015394:Molecular Structure; D011728:Pyridones / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050638:Receptors, Dopamine D4; D014018:Tissue Distribution
D001578:Benzopyrans; D065127:Dopamine D2 Receptor Antagonists; C493601:Drd4 protein, rat; D005462:Fluorine Radioisotopes; D011728:Pyridones; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4