Unlabelled: In recent years, monoamine oxidase B (MAO-B) inhibitors have become widely used in the treatment of early-stage Parkinson's disease. (11)C-l-deprenyl PET has been used by others to characterize MAO-B ligands in terms of their in vivo potency toward MAO-B and duration of action. In this study, we used (11)C-l-deprenyl PET to demonstrate the specific binding characteristics of the new irreversible selective MAO-B inhibitor rasagiline in 3 healthy volunteers.

Methods: The healthy volunteers received 1 mg of rasagiline daily for 10 d. Dynamic (11)C-l-deprenyl PET brain scans were acquired before the first treatment (scan 1) and immediately (scan 2), 2-3 wk (scan 3), and 4-6 wk (scan 4) after the final treatment.

Results: On scan 1, all subjects showed the highest l-deprenyl uptake in the thalamus and basal ganglia, with fairly high activity also in the cortex and cerebellum and much lower activity in the white matter. The areas of high uptake were absent from scan 2, on which activity throughout the brain was comparable to that in white matter, presumably because of blocking of MAO-B binding sites by rasagiline. Gradual recovery toward the baseline state was observed in the weeks after termination of treatment (scans 3 and 4).

Conclusion: (11)C-l-deprenyl PET showed binding of rasagiline to MAO-B, confirming blocking of MAO-B sites after 10 d of treatment with 1 mg of rasagiline per day, with immediate post-rasagiline treatment tracer uptake and metabolism in the basal ganglia compatible only with nonspecific binding. Subsequent gradual recovery was also seen, with return to near-baseline uptake. This finding is compatible with the known rate of de novo synthesis of MAO-B, confirming the irreversible binding of rasagiline.

Download full-text PDF

Source

Publication Analysis

Top Keywords

11c-l-deprenyl pet
20
monoamine oxidase
8
mao-b
8
basal ganglia
8
white matter
8
blocking mao-b
8
gradual recovery
8
binding rasagiline
8
mao-b confirming
8
rasagiline
7

Similar Publications

In the last decade, microfluidic techniques have been explored in radiochemistry, and some of them have been implemented in preclinical production. However, these are not suitable and reliable for preparing different types of radiotracers or dose-on-demand production. A fully automated iMiDEV™ microfluidic radiosynthesizer has been introduced and this study is aimed at using of the iMiDEV™ radiosynthesizer with a microfluidic cassette to produce [C]flumazenil and [C]-deprenyl.

View Article and Find Full Text PDF

Monoamine oxidase B (MAO-B) is a high-density protein in the brain mainly found on outer mitochondrial membranes, primarily in astroglia, but additionally in serotonergic neurons and in the substantia nigra in the midbrain. It is an enzyme that participates in the oxidative metabolism of important monoamines including dopamine, norepinephrine, benzylamine, and phenylethylamine. Elevated MAO-B density may be associated with astrogliosis and inhibiting MAO-B may reduce astrogliosis.

View Article and Find Full Text PDF

Three patients with neurological disorders (cerebral infarction, progressive multifocal leukoencephalopathy, and multiple sclerosis) underwent F-THK5351 and C-L-deprenyl PET on the same day to visualize lesions undergoing astrogliosis by measuring MAO-B activity. BPND map and SUV image with F-THK5351 as well as Ki map, Ki/K1 map and SUV image with C-L-deprenyl were created. F-THK5351 BPND maps and SUV images clearly identified the lesions undergoing astrogliosis.

View Article and Find Full Text PDF

Background: [C]-L-deprenyl-D 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.

Results: We performed two [C]-L-deprenyl-D scans for six healthy subjects and evaluated the test-retest variability of this radioligand.

View Article and Find Full Text PDF

An efficient preparation of labelling precursor of [C]L-deprenyl-D and automated radiosynthesis.

EJNMMI Radiopharm Chem

July 2017

1Centro Uruguayo de Imagenología Molecular (CUDIM), Av. Dr. Américo Ricaldoni 2010, 11600 Montevideo, Uruguay.

Background: The synthesis of [C]L-deprenyl-D for imaging of astrocytosis with positron emission tomography (PET) in neurodegenerative diseases has been previously reported. [C]L-deprenyl-D radiosynthesis requires a precursor, L-nordeprenyl-D, which has been previously synthesized from L-amphetamine as starting material with low overall yields. Here, we present an efficient synthesis of L-nordeprenyl-D organic precursor as free base and automated radiosynthesis of [C]L-deprenyl-D for PET imaging of astrocytosis.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!