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Quantitative Analysis of Norepinephrine Transporter in the Human Brain Using PET with (S,S)-¹⁸F-FMeNER-D₂

¹ Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; ² Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan; ³ Molecular Probe Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and ⁴ Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden

Correspondence: For correspondence or reprints contact: Hiroshi Ito, Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba, 263-8555, Japan. E-mail: hito{at}nirs.go.jp

(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). Conclusion: 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.

Key Words: norepinephrine transporter • (S,S)-¹⁸F-FMeNER-D₂ • positron emission tomography • human brain • thalamus

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