Mapping of the norepinephrine transporter in the human brain using PET with (S,S)-[18F]FMeNER-D2

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We have evaluated the detailed mapping of the norepinephrine transporter (NET) in the human brain with (S,S)-[18F]FMeNER-D2 using a template method and the generation of functional ROIs based on the PET information. Brain PET measurements were performed from 90 to 210 min after the injection of (S,S)-[18F]FMeNER-D2 in 20 healthy male subjects. Binding potential (BPND) was calculated as late time ratio of the target region to the reference region (caudate) minus one. BPND template images were generated from mean parametric images obtained in a group of 10 subjects using SPM2. On the BPND/MRI template images, functional ROIs based on several different BPND thresholds for the thalamus and brainstem were generated automatically using PMOD 2.8 software in addition to anatomical ROIs. PET/MRI data of another group of 10 subjects were used to evaluate the validity of the template method and the functional ROIs. NET BPND template images demonstrated higher binding in the medial thalamus whereas the anterior and the pulvinar divisions had lower binding. In the brainstem, high binding was detected around the cerebral aqueduct of the midbrain and within the dorsal pons, in a volume comprising locus coeruleus. Functional ROIs with higher BPND thresholds naturally yielded higher BPND and lower coefficients of variance than did anatomical ROIs. This study indicated that (S,S)-[18F]FMeNER-D2 combined with a template method provides detailed information on the distribution of NET in vivo and that functional ROIs on the template would be useful in further clinical studies.