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Eur J Nucl Med Mol Imaging. 2020 Feb;47(2):355-365. doi: 10.1007/s00259-019-04527-w. Epub 2019 Oct 12.

Characterization of the serotonin 2A receptor selective PET tracer (R)-[18F]MH.MZ in the human brain.

Author information

1
Center for Nuclear Medicine & PET/CT Positronmed, Providencia, 7501068, Santiago, Chile. vkramer@positronpharma.cl.
2
Positronpharma SA, Providencia, 7500921, Santiago, Chile. vkramer@positronpharma.cl.
3
Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.
4
Center for Nuclear Medicine & PET/CT Positronmed, Providencia, 7501068, Santiago, Chile.
5
Institute of Nuclear Chemistry, Johannes Gutenberg-University, Fritz-Strassmann-Weg 2, 55128, Mainz, Germany.
6
Positronpharma SA, Providencia, 7500921, Santiago, Chile.
7
Department of Drug Design and Pharmacology, University of Copenhagen, Jagtvej 160, 2100, Copenhagen, Denmark. matthias.herth@sund.ku.dk.
8
Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. matthias.herth@sund.ku.dk.

Abstract

PURPOSE:

The serotonin receptor subtype 2A antagonist (5-HT2AR) (R)-[18F]MH.MZ has in preclinical studies been identified as a promising PET imaging agent for quantification of cerebral 5-HT2ARs. It displays a very similar selectivity profile as [11C]MDL 100907, one of the most selective compounds identified thus far for the 5-HT2AR. As [11C]MDL 100907, (R)-[18F]MH.MZ also displays slow brain kinetics in various animal models; however, the half-life of fluorine-18 allows for long scan times and consequently, a more precise determination of 5-HT2AR binding could still be feasible. In this study, we aimed to evaluate the potential of (R)-[18F]MH.MZ PET to image and quantify the 5-HT2AR in the human brain in vivo.

METHODS:

Nine healthy volunteers underwent (R)-[18F]MH.MZ PET at baseline and four out of these also received a second PET scan, after ketanserin pretreatment. Regional time-activity curves of 17 brain regions were analyzed before and after pretreatment. We also investigated radiometabolism, time-dependent stability of outcomes measures, specificity of (R)-[18F]MH.MZ 5-HT2AR binding, and performance of different kinetic modeling approaches.

RESULTS:

Highest uptake was determined in 5-HT2AR rich regions with a BPND of approximately 1.5 in cortex regions. No radiometabolism was observed. 1TCM and 2TCM resulted in similar outcome measure, whereas reference tissue models resulted in a small, but predictable bias. (R)-[18F]MH.MZ binding conformed to the known distribution of 5-HT2AR and could be blocked by pretreatment with ketanserin. Moreover, outcomes measures were stable after 100-110 min.

CONCLUSION:

(R)-[18F]MH.MZ is a suitable PET tracer to image and quantify the 5-HT2AR system in humans. In comparison with [11C]MDL 100907, faster and more precise outcome measure could be obtained using (R)-[18F]MH.MZ. We believe that (R)-[18F]MH.MZ has the potential to become the antagonist radiotracer of choice to investigate the human 5-HT2AR system.

KEYWORDS:

5-HT2A receptor; Kinetic modeling; MDL 100907; Positron emission tomography (PET); [18F]MH.MZ

PMID:
31606832
DOI:
10.1007/s00259-019-04527-w

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