Improved synthesis and metabolic stability analysis of the dopamine transporter ligand [18F]FECT

Applications of Small-Animal Imaging in Neurology and Psychiatry

“…The technique has additionally been used to map regions responsive to levodopa in the 6-OHDA lesioned rat [ 71 ] 4 , indicating neuronal viability [ 6 ]. In PD patients, specifi c cortical-subcortical metabolic alterations have been described using [ 18 F]-FDG based on direct regional analysis [ 72 ] or network analysis approaches [ 73 ].…”

“…As such, they may provide surrogate markers and allow assessment of therapeutic interventions by using serial scans over an extended period in the same animal. Selective radioligands for many neurotransmitter receptors [ 3 ] and other cellular proteins [ 4 ], which act as enzyme substrates [ 5 ] or allow the interference of neuronal function [ 6 ], are available.…”

Fluorine-18 Radiolabeled PET Tracers for Imaging Monoamine Transporters: Dopamine, Serotonin, and Norepinephrine

“…An improved synthesis and metabolic stability analysis in rats of [ 18 F] 23 has recently been reported. [142] This work found that after 3 h plasma radioactivity consisted of ~93% intact [ 18 F] 23 and the radioactivity in homogenized cerebrum and cerebellum extracts each consisted of ~96% intact [ 18 F] 23 . Furthermore, there was no trace of [ 18 F]fluoroacetaldehyde or [ 18 F]fluoroacetic acid which would result from hydrolysis of the [ 18 F]fluoroethyl ester.…”

Synthesis and evaluation of novel tropane derivatives as potential PET imaging agents for the dopamine transporter

“…Numerous compounds labeled with 18 F have been evaluated for imaging DAT binding sites in the brain, and most of them are tropane derivatives. They include leading candidates such as [ 18 F]FECT 15 , [ 18 F]FP-CIT 16 , [ 18 F]FECNT 17, 18 , [ 18 F]FE-PE2I 19 and [ 18 F]LBT-999 20, 21 . It was reported that [ 18 F]FECNT displayed a high affinity and selectivity to human DAT, and the most favorable DAT binding kinetics in human studies, attaining quasi-equilibrium at 90 min post injection.…”

“…However, similar to [ 18 F]FECNT, [ 11 C]PE2I also undergoes in vivo metabolism forming polar components: two polar radiometabolites were found in the brain 28, 29 . Therefore, it can be expected that [ 18 F]FE-PE2I and [ 18 F]LBT-999 may also undergo similar metabolism 15, 30 . The objective of optimization of novel DAT imaging tracers is to improve the metabolic stability, while retaining the high affinity and selectivity to DAT.…”