Team Leader
Hisashi Doi D.Sci.

Laboratory for Labeling Chemistry

[Closed Mar. 2023]

E-mail hisashi.doi[at]riken.jp

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—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.

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 introducing¹¹C into carbon frameworks of bioactive small organic compounds by Pd⁰-mediated ¹¹C-methylationsusing [¹¹C]CH₃I. These labeling methods provides groundbreaking synthesis for introducing the [¹¹C]methyl group into a carbon framework in the very short time of 5 minutes. We are currently developing the stoichiometry-focused¹⁸F-labeling for medium molecules such asoligodeoxynucleotides by the application of Click chemistryand ¹¹C-acetylation for large molecules such as proteins.

In addition, our team is responsible for production of PET radiopharmaceuticals for clinical PET study in official and private hospitals.

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 original molecular probes and establish the probe library through developing the new labeling methodology.

Typical examples of C-11-radiolabeled molecules developed by our laboratory

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

Selected Publications

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 2021(29), 3970-3979 Fri Aug 06 00:00:00 JST 2021 doi: 10.1002/ejoc.202100638

Takatani S, Tahara T, Tsuji M, et al.
Synthesis of L-[5-¹¹ C]Leucine and L-α-[5-¹¹ C]Methylleucine via Pd⁰ -mediated ¹¹ C-Methylation and Microfluidic Hydrogenation: Potentiality of Leucine PET Probes for Tumor Imaging.
ChemMedChem Mon Jun 14 00:00:00 JST 2021 doi: 10.1002/cmdc.202100255

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 Sun Dec 01 00:00:00 JST 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 Fri Dec 01 00:00:00 JST 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 Thu Dec 01 00:00:00 JST 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 Tue Dec 01 00:00:00 JST 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 Sun Nov 01 00:00:00 JST 2015 doi: 10.1002/jlcr.3253

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 Thu Dec 01 00:00:00 JST 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 Tue Dec 01 00:00:00 JST 2009 doi: 10.1002/chem.200801974

Team LeaderHisashi Doi D.Sci.

—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 Theme

Selected Publications

Team Leader
Hisashi Doi D.Sci.

—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.