PET Radiopharmaceutical Sciences

Members

Theme Leader :
Jun Toyohara, Ph.D.
Researcher :
Muneyuki Sakata, Ph.D., Tetsuro Tago, Ph.D.
Adjunct Researcher :
Mikio Hiura, M.D., Ph.D., Yumi Yamamoto, Ph.D.

Keywords

Molecular imaging, PET tracer, First-in-human

Major Research Titles

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

Profile

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 11 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, [18F]MC225, and [18F]FSW-100) 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 pre-clinical whole-body PET/CT Si78 scanner installed in 2023. 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.

References

  1. Tago, T., Sakata, M., Kanazawa, M., Yamamoto, S., Ishii, K., Toyohara, J.: Preclinical validation of a novel brain-penetrant PET ligand for visualization of histone deacetylase 6: a potential imaging target for neurodegenerative diseases. Eur. J. Nucl. Med. Mol. Imaging., 2004 Mar 5. doi: 10.1007/s00259-024-06666-1.
  2. Toyohara, J., Sakata, M., Wagatsuma, K., Tago, T., Ishibashi, K., Ishii, K., Eslinga, P., Ishiwata, K.: Test-retest reproducibility of cerebral adenosine A2A receptor quantification using [11C]preladenant. Ann. Nucl. Med., 2022; 36(1):15-23.
  3. Toyohara, J., Sakata, M., Ishibashi, K., Mossel, P., Imai, M., Wagatsuma, K., Tago, T., Imabayashi, E., Colabufo, N.A., Luurtsema, G., Ishii, K.: First clinical assessment of [18F]MC225, a novel fluorine-18 labelled PET tracer for measuring functional P-glycoprotein at the blood-brain barrier. Ann. Nucl. Med., 2021; 35(11):1240-1252.
  4. Tago, T., Toyohara, J., Ishii, K.: Preclinical evaluation of an 18F-labeled SW-100 derivative for PET imaging of histone deacetylase 6 in the brain. ACS. Chem. Neurosci., 2021; 12(4):746-755.
  5. Tago, T., Toyohara, J., Fujimaki, R., Tatsuta, M., Song, R., Hirano, K., Iwai, K., Tanaka, H.: Effects of 18F-fluorinated neopentyl glycol side-chain on the biological characteristics of stilbene amyloid-b PET ligands. Nucl. Med. Biol., 2021; 48(8):2615-2623
  6. Toyohara, J., Nishino, K., Sakai, M., Tago, T., Oda, T.: Automated production of [18F]MK-6240 on CFN-MPS200. Appl. Radiat. Isot., 2021; 168:109468.
  7. Toyohara, J., Harada, N., Kakiuchi, T., Ohba, H., Kanazawa, M., Tago, T., Sakata, M., Ishiwata, K.: Synthesis and evaluation of N-isopropyl-p-[11C]methylamphetamine as a novel cerebral blood flow tracer for positron emission tomography. EJNMMI. Res., 2020; 10(1):115.
  8. Toyohara, J., Sakata, M., Tago, T., Colabufo, N.A., Luurtsema, G.: Automated synthesis, preclinical toxicity, and radiation dosimetry of [18F]MC225 for clinical use: a tracer for measuring P-glycoprotein function at the blood-brain barrier. EJNMMI. Res., 2020; 10(1):84.
  9. Tago, T., Toyohara, J., Ishii, K.: Radiosynthesis and preliminary evaluation of an 18F-labeled tubastatin A analog for PET imaging of histone deacetylase 6. J. Labelled. Comp. Radiopharm., 2020; 63(2):85-95.
  10. Toyohara, J., Yamamoto, H., Tago, T.: Searching for diagnostic properties of novel fluorine-18-labeled D-allose. Ann. Nucl. Med., 2019; 33(11):848-854.
  11. Tago, T., Toyohara, J., Sengoku, R., Murayama, S., Ishii, K.: Monoamine oxidase B binding of 18F-THK5351 to visualize glioblastoma and associated gliosis: an autopsy-confirmed case. Clin. Nucl. Med., 2019; 44(6):507-509.
  12. Tago, T., Toyohara, J., Harada, R., Furumoto, S., Okamura, N., Kudo, Y., Takahashi-Fujigasaki, J., Murayama, S., Ishii, K.: Characterization of the binding of tau imaging ligands to melanin-containing cells: putative off-target-binding site. Ann. Nucl. Med., 2019; 33(6): 375-382.
  13. Sakata, M., Toyohara, J., Ishibashi, K., Wagatsuma, K., Ishii, K., Zhang, M.R., Ishiwata, K.: Age and gender effects of 11C-ITMM binding to metabotropic glutamate receptor type 1 in healthy human participants. Neurobiol. Aging., 2017; 55:72-77.
  14. Sakata, M., Ishibashi, K., Imai, M., Wagatsuma, K., Ishii, K., Hatano, K., Ishiwata, K., Toyohara, J.: Assessment of safety, efficacy, and dosimetry of a novel 18-kDa translocator protein ligand, [11C]ITMM, in healthy human volunteers. EJNMMI. Res., 2017; 7(1):26.
  15. Sakata, M., Ishibashi, K., Imai, M., Wagatsuma, K, Ishii, K., Zhou, X., de Vries, E.F.J., Elsinga, P.H., Ishiwata, K., Toyohara, J.: Initial evaluation of an adenosine A2A receptor ligand, 11C-preladenat, in healthy human subjects. J. Nucl. Med., 2017; 58(9):1464-1470.
  16. Toyohara, J., Sakata, M., Hatano, K., Yanai, S., Endo, S., Ishibashi, K., Wagatsuma, K., Ishii, K., Ishiwata, K.: Preclinical and first-in-human studies of [11C]CB184 for imaging the 18-kDa translocator protein by positron emission tomography. Ann. Nucl. Med., 2016; 30(8):53334-543.
  17. 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(1):52-62.
  18. 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(8):1302-1307.
  19. Sakata, M., Oda, K., Toyohara, J., Ishii, K., Nariai, T., 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(3):285-296.
  20. 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(20:240-244.
  21. 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(20):240-244.
  22. Toyohara, J., Kobayashi, T., Mita, S., Ishiwata, K.: Application of [11C]SA4503 to selection of novel s1 selective agonists. Nucl. Med. Biol., 2012; 39(8):1117-1121.
  23. Toyohara, J., Sakata, M., Ishiwata, K.: Re-evaluation of in vivo selectivity of [11C]SA4503 to s1 receptors in the brain: contributions of emopamil binding protein. Nucl. Med. Biol., 2012; 39(7):1049-1052.
  24. 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(3):488-494.
  25. 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(8):1322-1328.
  26. 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(4):517-527.
  27. Sakata, M., Wu, J., Toyohara, J., Oda, K., Ishikawa, M., Ishii, K., Hashimoto, K., Ishiwata, K.: Biodistribution and radiation dosimetry of the a7 nicotinic acetylcholine receptor ligand [11C]CHIBA-1001 in humans. Nucl. Med. Biol., 2011; 38(3):443-448.
  28. 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(3):301-309.
  29. 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(3):301-309.