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Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

In this study, we evaluate the utility of 4-[18F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([18F]FITM) as a positron emission tomography (PET) ligand for imaging of the metabotropic glutamate receptor subtype 1 (mGluR1) in rat and monkey brains.

Methods

In vivo distribution of [18F]FITM in brains was evaluated by PET scans with or without the mGluR1-selective antagonist (JNJ16259685). Kinetic parameters of monkey PET data were obtained using the two-tissue compartment model with arterial blood sampling.

Results

In PET studies in rat and monkey brains, the highest uptake of radioactivity was in the cerebellum, followed by moderate uptake in the thalamus, hippocampus and striatum. The lowest uptake of radioactivity was detected in the pons. These uptakes in all brain regions were dramatically decreased by pre-administration of JNJ16259685. In kinetic analysis of monkey PET, the highest volume of distribution (V T ) was detected in the cerebellum (V T  = 11.5).

Conclusion

[18F]FITM has an excellent profile as a PET ligand for mGluR1 imaging. PET with [18F]FITM may prove useful for determining the regional distribution and density of mGluR1 and the mGluR1 occupancy of drugs in human brains.

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Acknowledgements

We thank Nobuki Nengaki and Masanao Ogawa (SHI Accelerator Service Co. Ltd.) for radiosynthesis, and Hidekatsu Wakizaka and Takashi Okauchi (National Institute of Radiological Sciences) for MRI and PET scans. We are also grateful to the staff of the National Institute of Radiological Sciences for assistance with the cyclotron operation and animal experiments.

This work was partly supported by a Grant-in-Aid for Basic Research (C) (Zhang MR, 22591379) from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese Government.

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Authors and Affiliations

  1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan

    Tomoteru Yamasaki, Masayuki Fujinaga, Jun Maeda, Kazunori Kawamura, Joji Yui, Akiko Hatori, Yuji Nagai, Masaki Tokunaga, Makoto Higuchi, Tetsuya Suhara, Toshimitsu Fukumura & Ming-Rong Zhang

  2. Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan

    Tomoteru Yamasaki

  3. SHI Accelerator Service Co. Ltd., Tokyo, Japan

    Yuichiro Yoshida

  4. Department of Molecular Probes, Molecular Imaging Centre, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan

    Ming-Rong Zhang

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  1. Tomoteru Yamasaki
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  2. Masayuki Fujinaga
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Correspondence to Ming-Rong Zhang.

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Yamasaki, T., Fujinaga, M., Maeda, J. et al. Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM. Eur J Nucl Med Mol Imaging 39, 632–641 (2012). https://doi.org/10.1007/s00259-011-1995-6

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  • DOI: https://doi.org/10.1007/s00259-011-1995-6

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