Laboratory for Labeling Chemistry | RIKEN BDR

Laboratory for Labeling Chemistry

Team Leader

Hisashi DoiD.Sci.

Photo of principal investigator

  • Location:Kobe / MI R&D Center Building
  • E-mail:hisashi.doi[at]riken.jpPlease replace [at] with @.

—Brightening Molecules—Synthesis of PET molecular probes of biologically important compounds such as drug candidates, and development of novel labeling chemistry to meet the increasing demands in PET science.

Research Summary

Our team is developing the general synthetic methodology of short-lived PET molecular probes for promotion of PET molecular imaging science. 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, we are striving toward introducing 11C into carbon frameworks of bioactive organic compounds by developing Pd0-mediated rapid C-[11C]methylations. These labeling methods provides groundbreaking synthesis for introducing the [11C]methyl group as the minimum carbon substituent into a carbon framework in the very short time of 5 minutes (Fig.1). We are currently expanding and evolving these rapid methylations from introduction of [11C]methyl group to [18F]fluoromethyl group, and furthermore developing the stoichiometry-focused 18F-labeling of oligodeoxynucleotides and peptides by the application of Click chemistry (Fig.2).
In the field of PET radiolabeling, the performance of the remote-controlled PET probe synthesizer is of key importance for realizing high quality and high yield in the synthesis of PET molecular probes. In this regard, we are also engaged in developing original PET probe synthesizers from the perspectives of not only safety and quick operation emphasized in labeling chemistry but also introducing advantages of experimental techniques ordinarily-used in organic chemistry. Thus, we seek to realize high quality RIKEN original molecular probes and establish the probe library through developing the new labeling methodology from the perspective of synthetically ideals and efficiencies based on organic chemistry (Fig.3).

In addition, our team is responsible for production of PET drugs for clinical PET study in three institutions including Osaka City University Hospital.

Research Theme

  • Development of PET-probe syntheses for drug candidates and novel labeling reactions
  • Development of radiolabeling system based on organic chemistry
  • Development of molecular probes associated with severe diseases such as cancer, inflammation, and neurological damage

Main Publications List

  • 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. 86–94 (2019) doi: 10.1002/jlcr.3700
  • Doi H, Kida T, Nishino K, et al.
    Solubility-Improved 10-O -Substituted SN-38 derivatives with Antitumor Activity
    ChemMedChem 12. 1715–1722 (2017) doi: 10.1002/cmdc.201700454
  • Doi H, Sato K, Shindou H, et al.
    Blood-Brain Barrier Permeability of Ginkgolide: Comparison of the Behavior of PET Probes 7α-{18 F]Fluoro- and 10-O -p -[11 C]Methylbenzyl Ginkgolide B in Monkey and Rat Brains
    Bioorganic & Medicinal Chemistry 24. 5148–5157 (2016) doi: 10.1016/j.bmc.2016.08.032
  • Doi H, Mawatari A, Kanazawa M, et al.
    Synthesis of 11 C-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
  • Doi H.
    Pd-mediated rapid cross-couplings using [11 C]methyl iodide: groundbreaking labeling methods in 11 C radiochemistry.
    Journal of Labelled Compounds and Radiopharmaceuticals 58(3). 73-85 (2015) doi: 10.1002/jlcr.3253
  • Doi H, Goto M, Suzuki M.
    Pd0 -Mediated Rapid C-[18 F]Fluoromethylation by the Cross-Coupling Reaction of a [18 F]Fluoromethyl Halide with an Arylboronic Acid Ester: Novel Method for the Synthesis of a 18 F-Labeled Molecular Probe for Positron Emission Tomography.
    Bulletin of the Chemical Society of Japan 85. 1233-1238 (2012) doi: 10.1246/bcsj.20120151
  • Kuboyama T, Nakahara M, Yoshino M, et al.
    Stoichiometry-focused 18F-labeling of alkyne-substituted oligodeoxynucleotides using azido([18 F]fluoromethyl)benzenes by Cu-catalyzed Huisgen reaction.
    Bioorganic & Medicinal Chemistry 19(1). 249-255 (2011) doi: 10.1016/j.bmc.2010.11.033
  • 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 [11 C]CH3 --C- and [18 F]FCH2 --C-Containing PET tracers (PET=positron emission tomography).
    Chemistry 15(16). 4165-4171 (2009) doi: 10.1002/chem.200801974
  • Doi H, Barletta J, Suzuki M, et al.
    Synthesis of 11 C-labelled N,N’ -diphenylurea and ethyl phenylcarbamate by a rhodium-promoted carbonylation via [11 C]isocyanatobenzene using phenyl azide and [11 C]carbon monoxide.
    Organic & Biomolecular Chemistry 2(21). 3063-3066 (2004) doi: 10.1039/B409294E
  • Suzuki M, Doi H, Bjorkman M, et al.
    Rapid Coupling of Methyl Iodide with Aryltributylstannanes Mediated by Palladium(0) Complexes: A General Protocol for the Synthesis of 11 CH3-Labeled PET Tracers.
    Chemistry - A European Journal 3(12). 2039-2042 (1997) doi: 10.1002/chem.19970031219

All Publications


Hisashi DoiTeam Leader hisashi.doi[at] CV
Tatsuya KidaResearch scientist t.kida[at] CV
Shuhei TakataniResearch scientist shuhei.takatani[at] CV
Yuzuru SatoResearch scientist yuzuru.sato[at]
Wakiko ArakakiTechnical Staff I wakiko.arakaki[at]
Ami IgesakaVisiting Technician ami.igesaka[at]
Kimiko UtsumiAssistant kimiko.utsumi[at]
Nami IkedaResearch Part-time Worker I nami.ikeda[at]

*:concurrent / Please replace [at] with @.