Quantitative analysis of norepinephrine transporter in the human brain using PET with (S,S)-18F-FMeNER-D2.
(S,S)-18F-FMeNER-D2 was recently developed as a radioligand for the measurement of norepinephrine transporter imaging with PET. In this study, a norepinephrine transporter was visualized in the human brain using this radioligand with PET and quantified by several methods.


METHODS
PET scans were performed on 10 healthy men after intravenous injection of (S,S)-18F-FMeNER-D2. Binding potential relative to nondisplaceable binding (BP(ND)) was quantified by the indirect kinetic, simplified reference-tissue model (SRTM), multilinear reference-tissue model (MRTM), and ratio methods. The indirect kinetic method was used as the gold standard and was compared with the SRTM method with scan times of 240 and 180 min, the MRTM method with a scan time of 240 min, and the ratio method with a time integration interval of 120-180 min. The caudate was used as reference brain region.


RESULTS
Regional radioactivity was highest in the thalamus and lowest in the caudate during PET scanning. BP(ND) values by the indirect kinetic method were 0.54 +/- 0.19 and 0.35 +/- 0.25 in the thalamus and locus coeruleus, respectively. BP(ND) values found by the SRTM, MRTM, and ratio methods agreed with the values demonstrated by the indirect kinetic method (r = 0.81-0.92).


CONCLUSIONS
The regional distribution of (S,S)-18F-FMeNER-D2 in our study agreed with that demonstrated by previous PET and postmortem studies of norepinephrine transporter in the human brain. The ratio method with a time integration interval of 120-180 min will be useful for clinical research of psychiatric disorders for estimation of norepinephrine transporter occupancy by antidepressants without requiring arterial blood sampling and dynamic PET.
Arakawa
Ryosuke
R
Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
Okumura
Masaki
M
Ito
Hiroshi
H
Seki
Chie
C
Takahashi
Hidehiko
H
Takano
Harumasa
H
Nakao
Ryuji
R
Suzuki
Kazutoshi
K
Okubo
Yoshiro
Y
Halldin
Christer
C
Suhara
Tetsuya
T
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005462:Fluorine Radioisotopes; D006801:Humans; D008024:Ligands; D008297:Male; D009025:Morpholines / Q000737:chemistry / Q000493:pharmacokinetics*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism
C506462:2-(alpha-(2-fluoromethoxyphenoxy)benzyl)morpholine; D005462:Fluorine Radioisotopes; D008024:Ligands; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals