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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 9/2016

01-08-2016 | Original Article

[11C]TASP457, a novel PET ligand for histamine H3 receptors in human brain

Authors: Yasuyuki Kimura, Chie Seki, Yoko Ikoma, Masanori Ichise, Kazunori Kawamura, Keisuke Takahata, Sho Moriguchi, Tomohisa Nagashima, Tatsuya Ishii, Soichiro Kitamura, Fumitoshi Niwa, Hironobu Endo, Makiko Yamada, Makoto Higuchi, Ming-Rong Zhang, Tetsuya Suhara

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 9/2016

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Abstract

Purpose

The histamine H3 receptors are presynaptic neuroreceptors that inhibit the release of histamine and other neurotransmitters. The receptors are considered a drug target for sleep disorders and neuropsychiatric disorders with cognitive decline. We developed a novel PET ligand for the H3 receptors, [11C]TASP0410457 ([11C]TASP457), with high affinity, selectivity and favorable kinetic properties in the monkey, and evaluated its kinetics and radiation safety profile for quantifying the H3 receptors in human brain.

Methods

Ten healthy men were scanned for 120 min with a PET scanner for brain quantification and three healthy men were scanned for radiation dosimetry after injection of 386 ± 6.2 MBq and 190 ± 7.5 MBq of [11C]TASP457, respectively. For brain quantification, arterial blood sampling and metabolite analysis were performed using high-performance liquid chromatography. Distribution volumes (V T) in brain regions were determined by compartment and graphical analyses using the Logan plot and Ichise multilinear analysis (MA1). For dosimetry, radiation absorbed doses were estimated using the Medical Internal Radiation Dose scheme.

Results

[11C]TASP457 PET showed high uptake (standardized uptake values in the range of about 3 – 6) in the brain and fast washout in cortical regions and slow washout in the pallidum. The two-tissue compartment model and graphical analyses estimated V T with excellent identification using 60-min scan data (about 16 mL/cm3 in the pallidum, 9 – 14 in the basal ganglia, 6 – 9 in cortical regions, and 5 in the pons), which represents the known distribution of histamine H3 receptors. For parametric imaging, MA1 is recommended because of minimal underestimation with small intersubject variability. The organs with the highest radiation doses were the pancreas, kidneys, and liver. The effective dose delivered by [11C]TASP457 was 6.9 μSv/MBq.

Conclusion

[11C]TASP457 is a useful novel PET ligand for the investigation of the density of histamine H3 receptors in human brain.
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Metadata
Title
[11C]TASP457, a novel PET ligand for histamine H3 receptors in human brain
Authors
Yasuyuki Kimura
Chie Seki
Yoko Ikoma
Masanori Ichise
Kazunori Kawamura
Keisuke Takahata
Sho Moriguchi
Tomohisa Nagashima
Tatsuya Ishii
Soichiro Kitamura
Fumitoshi Niwa
Hironobu Endo
Makiko Yamada
Makoto Higuchi
Ming-Rong Zhang
Tetsuya Suhara
Publication date
01-08-2016
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 9/2016
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-016-3332-6

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