PET Radiopharmaceutical Sciences

Theme Leader :
Jun Toyohara, Ph.D.
Researcher :
Muneyuki Sakata, Ph.D., Tetsuro Tago, Ph.D.
Adjunct Researcher :
Kiichi Ishiwata, Ph.D., Masahiro Mishina, M.D., Ph.D., Mikio Hiura, M.D., Ph.D., Yumi Yamamoto, Ph.D., Yuichi Kimura, Ph.D., Tadashi Nariai, M.D., Ph.D.

Molecular imaging, PET tracer, First-in-human

1. 1.Development of novel PET tracers for clinical use
2. 2.Research on small animal imaging.

1. Development of novel PET tracers for clinical use
Our research purposes are the development of novel PET tracers especially for neurodegenerative disorders and dementia, which develop frequently in elderly people. New PET tracers can provide new tools for research and exploration of the PET-based diagnosis of various diseases. For this purpose, we performed radio-synthesis of low molecular weight organic compounds with short half-lived positron emitters, basic biological evaluations of radiolabeled compounds, pre-clinical studies of candidates, and first-in-human clinical trials. So far nine novel PET tracers ([11C]SA4503, [11C]MPDX, [11C]TMSX, O-[11C]methyl-L-tyrosine, [11C]CHIBA-1001, [11C]4DST, [11C]ITMM, [11C]CB184, and [11C]Pleradenent) were subjected to first-in-human clinical trials by us.
Furthermore, we proceed the research by implementating various useful PET tracers developed by another institute and validate image analysis method to cooperate with the clinical PET diagnosis. In August 2014, our PET drug manufacturing facility was authenticated for production of [18F]Flutemetamol by Japanese Society of Nuclear Medicine.

2.Research on small animal imaging
We are studying physiological and pathological functions of small animals with PET tracer libraries and high-resolution small-animal dedicated semiconductor PET installed in January 2011. Furthermore, from June 2013, we introduced the 1T-bench top MRI for small animal, which will accelerate the multimodality molecular imaging researches in our institute.

1. 1. Okamoto, M., Shibayama, H., Naka, K., Kitagawa, Y., Ishiwata, K., Shimizu, I., Toyohara, J. : Optimization of the alkyl side chain length of fluorine-18-labelled 7α-alkyl-fluoroestradiol. Nucl. Med. Biol., 2016;43:512-519.
2. 2. Toyohara, J. : Importance of P-gp PET imaging in pharmacology. Curr. Pharm. Des., 2016;22:5830-5836.
3. 3. Toyohara, J., Okamoto, M., Aramaki, H., Zaitsu, Y., Shimizu, I., Ishiwata, K. : (R)-[11C]Emopamil as a novel tracer for imaging enhanced P-glycoprotein function. Nucl. Med. Biol., 2016; 43:52-62
4. 4. Okamoto, M., Naka, K., Kitagawa, Y., Ishiwata, K., Yoshimoto, M., Shimizu, I., Toyohara, J. : Synthesis and evaluation of 7α-(3-[18F]fluoropropyl) estradiol. Nucl. Med. Biol., 2015; 42:590-597.
5. 5. Hiura, M., Nariai, T., Ishii, K., Sakata, M., Oda, K., Toyohara, J., Ishiwata, K. : Changes in cerebral blood flow during steady-state cycling exercise: a study using oxygen-15-labeled water with PET. J. Cereb. Blood Flow Metab., 2014; 34:389-396.
6. 6. Toyohara, J., Sakata, M., Oda, K., Ishii, K., Ito, K., Hiura, M., Fujinaga, M., Yamasaki, T., Zhang, M.R., Ishiwata, K. : Initial human PET studies of metabotropic glutamate receptor type 1 ligand 11C-ITMM. J. Nucl. Med., 2013; 54:1302-1307.
7. 7. Sakata, M., Oda, K., Toyohara, J., Ishii, K., Nariai, T. and Ishiwata K. : Direct comparison of radiation dosimetry of six PET tracers using human whole-body imaging and murine biodistribution studies. Ann. Nucl. Med., 2013; 27:285-296.
8. 8. Toyohara, J., Sakata, M., Fujinaga, M., Yamasaki, T., Oda, K., Ishii, K., Zhang, M.R., Moriguchi Jeckel, C.M., Ishiwata, K. : Preclinical and the first clinical studies on [11C]ITMM for mapping metabotropic glutamate receptor subtype 1 by positron emission tomography. Nucl. Med. Biol., 2013; 40:214-220.
9. 9. Toyohara, J., Sakata, M., Oda, K., Ishii, K., Ishiwata, K. : Longitudinal observation of [11C]4DST uptake in turpentine-induced inflammatory tissue. Nucl. Med. Biol., 2013; 40:240-244.
10. 10. Toyohara, J., Kobayashi, T., Mita, S., Ishiwata, K. : Application of [11C]SA4503 to selection of novel σ1 selective agonists. Nucl. Med. Biol., 2012; 39:1117-1121.
11. 11. Mishina, M., Kimura, Y., Naganawa, M., Ishii, K., Oda, K., Sakata, M., Toyohara, J., Kobayashi, S., Katayama, Y., Ishiwata, K. : Differential effects of age on human striatal adenosine A1 and A2A receptors. Synapse, 2012; 66:832-839.
12. 12. Toyohara, J., Sakata, M., Ishiwata, K. : Re-evaluation of in vivo selectivity of [11C]SA4503 to σ1 receptors in the brain: contributions of emopamil binding protein. Nucl. Med. Biol., 2012; 39:1049-1052.
13. 13. Toyohara, J., Elsinga, P.H., Ishiwata, K., Sijbesma, J.W., Dierckx, R.A., van Waarde, A. : Evaluation of 4'-[methyl-11C]thiothymidine in a rodent tumor and inflammation model. J. Nucl. Med., 2012; 53:488-494.
14. 14. Toyohara, J., Nariai, T., Sakata, M., Oda, K., Ishii, K., Kawabe, T., Irie, T., Saga, T., Kubota, K., Ishiwata, K. : Whole-body distribution and brain tumor imaging with 11C-4DST: a pilot study. J. Nucl. Med., 2011; 52:1322-1328.
15. 15. Mishina, M., Ishiwata, K., Naganawa, M., Kimura, Y., Kitamura, S., Suzuki, M., Hashimoto, M., Ishibashi, K., Oda, K., Sakata, M., Hamamoto, M., Kobayashi, S., Katayama, Ishii, K. : Adenosine A2A receptors measured with [11C]TMSX PET in the striata of Parkinson's disease. PLoSOne, 2011; 6:e17338.
16. 16. Toyohara, J., Ishiwata, K., Sakata, M., Wu, J., Nishiyama, S., Tsukada, H., Hashimoto, K. : In vivo evaluation of carbon-11-labelled non-sarcosine-based glycine transporter 1 inhibitors in mice and conscious monkeys. Nucl. Med. Biol., 2011; 38:517-527.
17. 17. Sakata, M., Wu, J., Toyohara, J., Oda, K., Ishikawa, M., Ishii, K., Hashimoto, K., Ishiwata, K. : Biodistribution and radiation dosimetry of the α7 nicotinic acetylcholine receptor ligand [11C]CHIBA-1001 in humans. Nucl. Med. Biol., 2011; 38:443-448.
18. 18. Toyohara, J., Ishiwata, K., Sakata, M., Wu, J., Nishiyama, S., Tsukada, H., Hashimoto, K. : In vivo evaluation of alpha7 nicotinic acetylcholine receptor agonists [11C]A-582941 and [11C]A-844606 in mice and conscious monkeys. PLoSOne, 2010; 5:e8961.
19. 19. Toyohara, J., Sakata, M., Wu, J., Ishikawa, M., Oda, K., Ishii, K., Iyo, M., Hashimoto, K., Ishiwata, K. : Preclinical and the first clinical studies on [11C]CHIBA-1001 for mapping alpha7 nicotinic receptors by positron emission tomography. Ann. Nucl. Med., 2009; 23:301-309.