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

This paper describes pharmacokinetic analyses of the monoamine-oxidase-B (MAO-B) radiotracer [ ¹⁸ F]( S )-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline ([ ¹⁸ F]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 ([ ¹¹ C]PiB) and tau ([ ¹⁸ F]flortaucipir) imaging assessments underwent dynamic [ ¹⁸ F]SMBT-1 PET imaging with arterial input function determination. [ ¹⁸ F]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 [ ¹⁸ F]SMBT-1 kinetics. The 2TC total volume of distribution (V _T ) was well identified and highly correlated (r ² ∼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 (∼10%), representing a practical alternative for [ ¹⁸ F]SMBT-1 analyses.
Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.