Synthesis and in vivo evaluation of [(18)F]2-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)-dione ([(18)F]FECUMI-101) as an imaging probe for 5-HT1A receptor agonist in nonhuman primates.
Synthesis and in vivo evaluation of [(18)F]2-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)-dione ([(18)F]FECUMI-101) as an imaging probe for 5-HT1A receptor agonist in nonhuman primates.
复制标题
DOI：
10.1016/j.bmc.2013.05.050
复制
发表时间：
2013-09-01
影响因子：
3.5
通讯作者：
Kumar JS
中科院分区：
文献类型：
--
作者：
Majo VJ;Milak MS;Prabhakaran J;Mali P;Savenkova L;Simpson NR;Mann JJ;Parsey RV;Kumar JS
The 5-HT1AR partial agonist PET radiotracer, [11C]CUMI-101, has advantages over an antagonist radiotracer as it binds preferentially to the high affinity state of the receptor and thereby provides more functionally meaningful information. The major drawback of C-11 tracers is the lack of cyclotron facility in many health care centers thereby limiting widespread clinical or research use. We identified the fluoroethyl derivative, 2-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione (FECUMI-101) (Ki = 0.1 nM; Emax = 77%; EC50 = 0.65 nM) as a partial agonist 5-HT1AR ligand of the parent ligand CUMI-101. FECUMI-101 is radiolabeled with F-18 by O-fluoroethylation of the corresponding desmethyl analogue (1) with [18F]fluoroethyltosylate in DMSO in the presence of 1.6 equiv. of K2CO3 in 45 ± 5% yield (EOS). PET shows [18F]FECUMI-101 binds specifically to 5-HT1AR enriched brain regions of baboon. The specificity of [18F]FECUMI-101 binding to 5-HT1AR was confirmed by challenge studies with the known 5-HT1AR ligand WAY100,635. These findings indicate that [18F]FECUMI-101 can be a viable agonist ligand for the in vivo quantification of high affinity 5-HT1AR with PET.
登录
查看更多内容
影响因子：
1.8
作者：
Bauman, A;Piel, M;Rösch, F
通讯作者：
Rösch, F
影响因子：
3.5
作者：
Champion, C.;Le Loirec, C.
通讯作者：
Le Loirec, C.
影响因子：
5
作者：
Herth, Matthias M.;Volk, Balazs;Kristensen, Jesper
通讯作者：
Kristensen, Jesper
影响因子：
2.3
作者：
COHN, JB;RICKELS, K;STEEGE, JF
通讯作者：
STEEGE, JF
影响因子：
4.2
作者：
Burnet, PWJ;Eastwood, SL;Harrison, PJ
通讯作者：
Harrison, PJ