RT Journal Article
SR Electronic
T1 Development of [18F]FEMPT, a high affinity PET tracer for 5-HT1AR.
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1546
OP 1546
VO 56
IS supplement 3
A1 Kumar, JS Dileep
A1 Arango, Victoria
A1 Majo, Vattoly
A1 Simpson, Norman
A1 Underwood, Mark
A1 Kassir, Suham
A1 Liang, Steven
A1 Collier, Thomas
A1 Vasdev, Neil
A1 Mann, John
YR 2015
UL http://jnm.snmjournals.org/content/56/supplement_3/1546.abstract
AB 1546 Objectives The development of 5-HT1AR agonist PET tracers for the past 2 decades has met with limited success. Through the structure activity relationship studies of arylpiperazine derivatives of 3,5-dioxo-(2H,4H)-1,2,4-triazine, we found 2-(4-(4-(7-(2-fluoroethoxy)naphthalen-1-yl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)-dione (FEMPT) as a high affinity 5-HT1AR ligand. This study describes the radiosynthesis and evaluation of [18F]FEMPT as a selective high affinity PET radiotracer for 5-HT1AR.Methods The reference standard FEMPT and the corresponding radiolabeling precursor were synthesized from 4-methyl-2H-[1,2,4]triazine-3,5-dione. Radiosynthesis of [18F]FEMPT was achieved by reacting des-fluoroethoxy precursor with [18F]CH2CH2OTs. In vitro autoradiography studies of [18F]FEMPT were performed in postmortem human brain tissue sections. The specific binding of the [18F]FEMPT binding was determined by co-incubating the adjacent sections with the known 5-HT1AR ligand WAY100635.Results The syntheses of FEMPT and its radiolabeling precursor proceeded in 4 steps from commercial 4-methyl-2H-[1,2,4]triazine-3,5-dione with 40% overall yield. FEMPT shows a Ki 0.1 nM to 5-HT1AR and an Emax 95% based on GTPgS binding assays of CHO cells expressing 5-HT1AR. FEMPT has no significant affinity to a variety of brain targets. The radiosynthesis of [18F]FEMPT was achieved in 25+5% yield at EOS. Autoradiography studies reveals higher binding of [18F]FEMPT in hippocampal CA1 and prefrontal cortex brain regions in comparison to cerebellum.Conclusions FEMPT, a high affinity and selective 5-HT1AR ligand amenable for radiolabeling with [18F] isotope is identified, synthesized and radiolabeled. The details of radiosynthesis and in vitro and in vivo evaluations of the radioligand will be presented.Research Support MH062185