Simplified quantification and whole-body distribution of [18F]FE-PE2I in nonhuman primates: prediction for human studies.
BACKGROUND
[(18)F]FE-PE2I is a promising dopamine transporter (DAT) radioligand. In nonhuman primates, we examined the accuracy of simplified quantification methods and the estimates of radiation dose of [(18)F]FE-PE2I.


METHODS
In the quantification study, binding potential (BP(ND)) values previously reported in three rhesus monkeys using kinetic and graphical analyses of [(18)F]FE-PE2I were used for comparison. BP(ND) using the cerebellum as reference region was obtained with four reference tissue methods applied to the [(18)F]FE-PE2I data that were compared with the kinetic and graphical analyses. In the whole-body study, estimates of adsorbed radiation were obtained in two cynomolgus monkeys.


RESULTS
All reference tissue methods provided BP(ND) values within 5% of the values obtained with the kinetic and graphical analyses. The shortest imaging time for stable BP(ND) estimation was 54 min. The average effective dose of [(18)F]FE-PE2I was 0.021 mSv/MBq, similar to 2-deoxy-2-[(18)F]fluoro-d-glucose.


CONCLUSIONS
The results in nonhuman primates suggest that [(18)F]FE-PE2I is suitable for accurate and stable DAT quantification, and its radiation dose estimates would allow for a maximal administered radioactivity of 476 MBq in human subjects.
Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, SE-17176 Stockholm, Sweden. andrea.varrone@ki.se
Andrea
A
Varrone
Balázs
B
Gulyás
Akihiro
A
Takano
Michael G
MG
Stabin
Cathrine
C
Jonsson
Christer
C
Halldin
D000818:Animals; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D009662:Nortropanes / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D011829:Radiation Dosage; D014018:Tissue Distribution; D051598:Whole Body Imaging / Q000379:methods*
C543996:(E)-N-(3-iodoprop-2-enyl)-2beta-carbofluoroethoxy-3beta-(4'-methyl-phenyl) nortropane; D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D009662:Nortropanes