Abstract
Background[11C]-l-deprenyl-D2 is a positron emission tomography (PET) radioligand for measurement of the monoamine oxidase B (MAO-B) activity in vivo brain. The estimation of the test-retest reproducibility is important for accurate interpretation of PET studies.ResultsWe performed two [11C]-l-deprenyl-D2 scans for six healthy subjects and evaluated the test-retest variability of this radioligand. MAO-B binding was quantified by two tissue compartment model (2TCM) with three rate constants (K1, k2, k3) using metabolite-corrected plasma radioactivity. The λk3 defined as (K1/k2) × k3 was also calculated. The correlation between MAO-B binding and age, and the effect of partial volume effect correction (PVEc) for the reproducibility were also estimated. %difference of k3 was 2.6% (medial frontal cortex) to 10.3% (hippocampus), and that of λk3 was 5.0% (thalamus) to 9.2% (cerebellum). Mean %difference of all regions were 5.3 and 7.0% in k3 and λk3, respectively. All regions showed below 10% variabilities except the hippocampus in k3 (10.3%). Intraclass correlation coefficient (ICC) of k3 was 0.78 (hippocampus) to 0.98 (medial frontal cortex), and that of λk3 was 0.78 (hippocampus) to 0.95 (thalamus). Mean ICC were 0.94 and 0.89 in k3 and λk3, respectively. The highest positive correlation with age was observed in the hippocampus, as r = 0.75 in k3 and 0.76 in λk3. After PVEc, mean %difference were 5.6 and 7.2% in k3 and λk3, respectively. Mean ICC were 0.92 and 0.90 for k3 and λk3, respectively. These values were almost the same as those before PVEc.ConclusionsThe present results indicate that k3 and λk3 of [11C]-l-deprenyl-D2 are reliable parameters for test-retest reproducibility with healthy subjects both before and after PVEc. The studies with patients of larger sample size are required for further clinical applications.
Highlights
Monoamine oxidase (MAO) is an enzyme of deamination of monoamine and exists in two isoforms, MAO-A and monoamine oxidase B (MAO-B)
Test-retest variability Mean and SD values of six subjects in PET1 and PET2, mean and range of %differences, and Intraclass correlation coefficient (ICC) in all regions are shown in Table 1. %difference of k3 was 2.6% to 10.3%, and that of λk3 was 5.0% to 9.2%
The study reported that oral administrations of 1–5 mg sembragiline induced near-maximal inhibition of brain MAO-B, and MAO-B
Summary
Monoamine oxidase (MAO) is an enzyme of deamination of monoamine and exists in two isoforms, MAO-A and MAO-B. MAO-B is considered as a major enzyme in dopamine metabolism in the human brain, and MAOB inhibitors are used for the treatment of Parkinson’s disease to increase the dopamine level [1]. [11C]-L-deprenyl-D2 is a positron emission tomography (PET) radioligand for measurement of the MAO-B activity in the brain [7]. This radioligand was used for many PET studies to evaluate MAO-B inhibitors’ occupancy [8, 9], pathology of AD [10,11,12], amyotrophic lateral sclerosis (ALS) [13], traumatic brain injury [14], and epilepsy [15,16,17]. In addition to the clinical studies, [11C]-L-deprenyl-D2 showed good result reproducibility in a test-retest protocol [18].
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