Compartmental modeling of [(11)C]MENET binding to the norepinephrine transporter in the healthy human brain

Dysregulation of the noradrenergic system has been implicated in a number of neurological conditions such as Parkinson's and Alzheimer's. [(11)C]MENET is a novel PET radiotracer with high affinity and selectivity for the norepinephrine transporter. The applicability of different kinetic models on [(11)C]MENET PET image quantification in healthy population is evaluated.

Six healthy volunteers (mean age: 54years) were recruited for the study, five of whom underwent arterial sampling for measurement of the input function. Ninety minute dynamic PET scans were obtained on a high resolution research tomograph with 15mCi of [(11)C]MENET injected at the scan start time. Regions of interest were delineated on the PET scan aided by the corresponding MRI image for anatomical guidance. Distribution volumes and their ratios (DVRs) with respect to the occipital reference tissue were calculated using the full arterial model (FAM), the simplified reference tissue model (SRTM) and the multilinear reference tissue model (MRTM2).

Among the FAMs, the single-tissue model was found to be statistically superior to the two-tissue model. [(11)C]MENET focal uptake was observed in the NET-rich regions of the brainstem and subcortical regions including the thalamus, locus cereleus and the raphe nuclei. Highest DVRs were observed in the locus cereleus (mean±standard deviation: 1.39±0.25) and red nucleus (1.35±0.25). DVRs of the thalamus were in good agreement between FAM (1.26±0.13), SRTM (1.23±0.15) and MRTM2 (1.21±0.14). Comparing the FAM to the SRTM and MRTM2, DVRs were underestimated in the thalamus by 3 and 4% on average, respectively.

The single-tissue compartmental model was sufficient in describing the [(11)C]MENET kinetics in the healthy human brain. SRTM and MRTM2 present themselves as attractive options for estimating NET DVR using an occipital reference region.