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

• Published in: Journal of cerebral blood flow and metabolism Vol. 44; no. 11; pp. 1262 - 1276
• Main Authors: Lopresti, Brian J, Stehouwer, Jeffrey, Reese, Alexandria C, Mason, Neale S, Royse, Sarah K, Narendran, Rajesh, Laymon, Charles M, Lopez, Oscar L, Cohen, Ann D, Mathis, Chester A, Villemagne, Victor L
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.11.2024
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Brain - diagnostic imaging; Brain - metabolism; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - metabolism; Female; Fluorine Radioisotopes; Humans; Kinetics; Male; Middle Aged; Monoamine Oxidase - analysis; Monoamine Oxidase - metabolism; Original; Positron-Emission Tomography - methods; Quinolines - pharmacokinetics; Radiopharmaceuticals - pharmacokinetics; neurodegeneration; monoamine oxidase-B; astrogliosis; Alzheimer’s disease; Positron emission tomography
• ISSN: 0271-678X; 1559-7016; 1559-7016
• DOI: 10.1177/0271678X241254679

This paper describes pharmacokinetic analyses of the monoamine-oxidase-B (MAO-B) radiotracer [18F](S)-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline ([18F]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 ([11C]PiB) and tau ([18F]flortaucipir) imaging assessments underwent dynamic [18F]SMBT-1 PET imaging with arterial input function determination. [18F]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 K1/k2 ratio was fixed to a whole brain value best described [18F]SMBT-1 kinetics. The 2TC total volume of distribution (VT) was well identified and highly correlated (r2∼0.8) with post-mortem MAO-B indices. Cerebellar grey matter (CGM) showed the lowest mean VT 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 (r2 > 0.9) but with varying bias. We found the CGM-normalized 70–90 min SUVR to be highly correlated (r2 = 0.93) with the 2TC distribution volume ratio (DVR) with acceptable bias (∼10%), representing a practical alternative for [18F]SMBT-1 analyses.