Whole-body biodistribution and radiation dosimetry estimates for the PET dopamine transporter probe 18F-FECNT in non-human primates

Abstract

Background and aim-2β-Carbomethoxy-3-(4-chlorophenyl)-8-(2-[ 18 F]fluoroethyl)nortropane ( 18 F-FECNT) is a selective radioligand for the in vivo quantification of dopamine transporters by using positron emission tomography. The aim of the current study was to quantify the distribution of radioactivity in three rhesus monkeys after the injection of approximately 185 MBq (5 mCi) of 18 F-FECNT.

Whole-body biodistribution, radiation dosimetry estimates for the PET norepinephrine transporter probe (S,S)-[18F]FMeNER-D2 in non-human primates

“…The calculated dosimetry results seem comparable with those for other 18 F labelled brain imaging agents [22,23].…”

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

“…Compound [ 18 F] 18 has since been used to measure DAT occupancy of cocaine[128] and radiation dosimetry studies have been performed in rats and monkeys. [129,130] Two different automated radiosynthesis methods of [ 18 F] 18 have been reported. [131,132] Initial studies[133] in 6 healthy humans with [ 18 F] 18 showed that the time for peak uptake in the caudate and putamen was in the range of 70–130 min with caudate-to-cerebellum ratios of 7.6–10.5 and putamen-to-cerebellum ratios of 7.1–9.3.…”

Synthesis, Fluorine-18 Radiolabeling, and Biological Evaluation of N-((E)-4-Fluorobut-2-en-1-yl)-2β-carbomethoxy-3β-(4′-halophenyl)nortropanes: Candidate Radioligands for In Vivo Imaging of the Brain Dopamine Transporter with Positron Emission Tomography

“…Numerous other fluorinated derivatives of 1 − 6 , which contain the 18 F-radiolabel as an N -fluoroalkyl group or an O -fluoroalkyl ester have also been prepared and evaluated . Among the numerous derivatives reported, compounds 7 (FECNT) and 8 (FPCIT) emerged as viable DAT PET tracers and have found use in human PET imaging. − Both compounds [ 18 F] 7 and [ 18 F] 8 achieve a high uptake and specific binding in the putamen and caudate but neither compound washes out significantly during the course of the study, which is needed to enable kinetic modeling of the tracer behavior. , Compound 8 also has a higher binding affinity at the serotonin transporter (SERT) than the DAT, and so [ 18 F] 8 is not a DAT-specific PET tracer. Additionally, [ 18 F] 8 defluorinates, which is similar to other tracers containing an [ 18 F]fluoropropyl group, − whereas [ 18 F] 7 is metabolized to a polar radiometabolite, which can cross the blood−brain barrier (a similar result was recently reported for the amyloid imaging agent [ 18 F]FDDNP).…”

“…41 Among the numerous derivatives reported, compounds 7 (FECNT) 42 and 8 (FPCIT) 43 emerged as viable DAT PET tracers and have found use in human PET imaging. [44][45][46][47][48][49][50] Both compounds [ 18 F]7 and [ 18 F]8 achieve a high uptake and specific binding in the putamen and caudate but neither compound washes out significantly during the course of the study, which is needed to enable kinetic modeling of the tracer behavior. 51,52 Compound 8 also has a higher binding affinity at the serotonin transporter (SERT) than the DAT, 53 and so [ 18 F]8 is not a DAT-specific PET tracer.…”