RIKEN Center for Biosystems Dynamics Research Laboratory for Labeling Chemistry

Team Leader: Hisashi Doi (D.Sc.)

Japanese Page

Research Summary

With the objective of applying the potentials of organic chemistry to life science, we seek to realize the new synthetic methodology of PET molecular probes by using organometallic catalysts such as Pd, Rh, and Cu, etc., as one of our main projects. Especially, we focus on the labeling methods by carbon-carbon bond formation which would provide chemical and metabolic stability of PET molecular probe in in vivo system to enhance the credibility of the PET imaging. In addition, our team is working on developing¹¹C- or¹⁸F-labeling methods for biomolecules such as peptides, oligonucleotide, proteins, and antibodies. In addition, our team is responsible for production of PET drugs for human PET study in three institutions including Kobe City Medical Center General Hospital.

Main Research Fields

Chemistry

Related Research Fields

Engineering
Biological Sciences
Medicine, Dentistry & Pharmacy

Keywords

PET imaging
Rapid chemical reaction
Organometallic chemistry
Synthesis of PET molecular probe
Drug candidate

Selected Publications

1. Kida T., Takahashi N., Mori M. X., et al.
"N-Methylamide-Structured SB366791 Derivatives with High TRPV1 Antagonistic Activity: Toward PET Radiotracers to Visualize TRPV1"
RSC Medicinal Chemistry 13(10), 1197–1204 (2022) doi: 10.1039/d2md00158f
2. Takatani S., Tahara T., Tsuji M., et al.
"Synthesis of L-[5-¹¹C]Leucine and L-α-[5-¹¹C]Methylleucine via Pd⁰-mediated ¹¹C-Methylation and Microfluidic Hydrogenation: Potentiality of Leucine PET Probes for Tumor Imaging"
ChemMedChem 16(21), 3271-3279(2021). doi: 10.1002/cmdc.202100255
3. Doi H., Goto M., Sato.Y.
"Pd⁰-Mediated Cross-Coupling of [¹¹C]Methyl Iodide with Carboxysilane for Synthesis of [¹¹C]Acetic Acid and Its Active Esters: ¹¹C-Acetylation of Small, Medium, and Large Molecules"
European Journal of Organic Chemistry, 3970–3979, (2021). doi: 10.1002/ejoc.202100638
4. Goto M., Nishiyama A., Yamaguchi T., et al.
"Synthesis of ¹¹C-labeled ubiquinone and ubiquinol via Pd⁰-mediated rapid C-[¹¹C]methylation using [¹¹C]methyl iodide and 39-demethyl-39-(pinacolboryl)ubiquinone."
Journal of Labelled Compounds and Radiopharmaceuticals 62(2). 86–94 (2019) doi: 10.1002/jlcr.3700
5. Doi H., Kida T., Nishino K., et al.
"Solubility-Improved 10-O-Substituted SN-38 Derivatives with Antitumor Activity"
ChemMedChem 12(20). 1715-1722 (2017) doi: 10.1002/cmdc.201700454
6. Doi H., Sato K., Shindou H., et al.
"Blood-Brain Barrier Permeability of Ginkgolide: Comparison of the Behavior of PET Probes 7α-[¹⁸F]Fluoro- and 10-O-p-[¹¹C]Methylbenzyl Ginkgolide B in Monkey and Rat Brains"
Bioorganic & Medicinal Chemistry 24(21). 5148–5157 (2016) doi: 10.1016/j.bmc.2016.08.032
7. Doi H., Mawatari A., Kanazawa M., et al.
"Synthesis of ¹¹C-Labeled Thiamine and Fursultiamine for in Vivo Molecular Imaging of Vitamin B₁ and Its Prodrug Using Positron Emission Tomography."
The Journal of Organic Chemistry 80(12). 6250-6258 (2015) doi: 10.1021/acs.joc.5b00685
8. Doi H.
"Pd-mediated rapid cross-couplings using [¹¹C]methyl iodide: groundbreaking labeling methods in ¹¹C radiochemistry.
Journal of Labelled Compounds and Radiopharmaceuticals 58(3). 73-85 (2015) doi: 10.1002/jlcr.3253
9. Doi H., Goto M., Suzuki M.
"Pd⁰-Mediated Rapid C-[¹⁸F]Fluoromethylation by the Cross-Coupling Reaction of a [¹⁸F]Fluoromethyl Halide with an Arylboronic Acid Ester: Novel Method for the Synthesis of a ¹⁸F-Labeled Molecular Probe for Positron Emission Tomography."
Bulletin of the Chemical Society of Japan 85(11). 1233-1238 (2012) doi: 10.1246/bcsj.20120151
10. Doi H., Ban I., Nonoyama A., et al.
"Palladium(0)-mediated rapid methylation and fluoromethylation on carbon frameworks by reacting methyl and fluoromethyl iodide with aryl and alkenyl boronic acid esters: useful for the synthesis of [¹¹C]CH₃–C- and [¹⁸F]FCH₂–C-Containing PET tracers (PET=positron emission tomography)."
Chemistry —A European Journal 15(16). 4165-4171 (2009) doi: 10.1002/chem.200801974

Lab Members

Principal investigator

Hisashi Doi: Team Leader

Core members

Tatsuya Kida: Research Scientist
Shuhei Takatani: Research Scientist
Yuzuru Sato: Research Scientist
Wakiko Arakaki: Technical Staff I
Ami Igesaka: Visiting Technician
Kimiko Utsumi: Assistant

Contact Information

6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan
Tel: +81-(0)78-304-7130
Fax: +81-(0)78-304-7131
Email: hisashi.doi [at] riken.jp