Kinetic modeling of the monoamine oxidase-B radioligand [18F]SMBT-1 in human brain with positron emission tomography

This paper describes pharmacokinetic analyses of the monoamine-oxidase-B (MAO-B) radiotracer [F-18](S)-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline ([F-18]SMBT-1) for positron emission tomography (PET) brain imaging. Brain MAO-B expression is widespread, predominantly within astrocytes. Reactive astrogliosis in response to neurodegenerative disease pathology is associated with MAO-B overexpression. Fourteen elderly subjects (8 control, 5 mild cognitive impairment, 1 Alzheimer's disease) with amyloid ([C-11]PiB) and tau ([F-18]flortaucipir) imaging assessments underwent dynamic [F-18]SMBT-1 PET imaging with arterial input function determination. [F-18]SMBT-1 showed high brain uptake and a retention pattern consistent with the known MAO-B distribution. A two-tissue compartment (2TC) model where the K-1/k(2) ratio was fixed to a whole brain value best described [F-18]SMBT-1 kinetics. The 2TC total volume of distribution (V-T) was well identified and highly correlated (r(2)similar to 0.8) with post-mortem MAO-B indices. Cerebellar grey matter (CGM) showed the lowest mean V-T of any region and is considered the optimal pseudo-reference region. Simplified analysis methods including reference tissue models, non-compartmental models, and standard uptake value ratios (SUVR) agreed with 2TC outcomes (r(2) > 0.9) but with varying bias. We found the CGM-normalized 70-90 min SUVR to be highly correlated (r(2) = 0.93) with the 2TC distribution volume ratio (DVR) with acceptable bias (similar to 10%), representing a practical alternative for [F-18]SMBT-1 analyses.