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

Abstract

This review focuses on the development of fluorine-18 radiolabeled PET tracers for imaging the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET). All successful DAT PET tracers reported to date are members of the 3β-phenyl tropane class and are synthesized from cocaine. Currently available carbon-11 SERT PET tracers come from both the diphenylsulfide and 3β-phenyl nortropane class, but so far only the nortropanes have found success with fluorine-18 derivatives. NET imaging has so far employed carbon-11 and fluorine-18 derivatives of reboxetine but due to defluorination of the fluorine-18 derivatives further research is still necessary.

Figure 1

Structures of GBR-based DAT PET tracers.

Fig 2

Cocaine, 4′-Fluorococaine, and 3β-Phenyl Tropane-Based Dopamine Transporter Ligands.

Figure 3

3β-Phenyl Tropane-Based Dopamine Transporter Ligands.

Fig 4

Binding Affinities of 29–32 At Transfected Human Monoamine Transporters.

Figure 5

SERT Ligands.

Fig 6

Diaryl Sulfide-Based Serotonin Transporter Ligands.

Figure 7

Diaryl Sulfide-Based Serotonin Transporter Ligands.

Figure 8

Fluoroethyl Ester Nortropane-based SERT Ligands.

Figure 9

MicroPET time-activity curves obtained by injection of [¹⁸F]68 (left) and [¹⁸F]69 (right) into anesthetized cynomolgus monkeys.

Figure 10

HRRT PET images obtained by injection of [¹⁸F]68 (left) and [¹⁸F]69 (right) into an awake rhesus monkey.

Fig 11

(S,S)-Reboxetine Derivative-Based Norepinephrine Transporter Ligands.