Labelling Chemistry Team

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 developing ¹¹C- or ¹⁸F-labeling methods for biomolecules such as peptides, oligonucleotide, proteins, and antibodies.

Research Fields

Engineering / Chemistry / Pharmacology & Toxicology

Research Subjects

• Development of PET-probe syntheses for drug candidates and novel labeling reactions
• Development of remote-controlled synthesizers and efficient synthetic procedures for radiolabeling by organometallic chemistry
• Development of molecular probes associated with severe diseases such as cancer, inflammation, and neurological damage

Publications

1. Doi, H., Goto, M. and 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"
   Bull. Chem. Soc. Jpn. 85, 1233–1238 (2012).
2. Kuboyama, T., Nakahara, M., Yoshino, M., Cui, Y., Sako, T., Wada, Y., Imanishi, T., Obika, S., Watanabe, Y., Suzuki, M. and Doi, H.:
   "Stoichiometry-Focused ¹⁸F-Labeling of Alkyne-Substituted Oligodeoxynucleotides Using Azido([¹⁸F]fluoromethyl)benzenes by Cu-Catalyzed Huisgen Reaction"
   Bioorg. Med. Chem., 19, 249–255 (2011).
3. Suzuki, M. and Doi, H.:
   "Pd⁰-Mediated Rapid C-[¹¹C]Methylations and C-[¹⁸F]Fluoromethylations: Revolutionary New Methodologies for the Synthesis of Short-Lived PET Molecular Probes"
   J. Synth. Org. Chem. Jpn., 68(11), 1195–1206 (2010).
4. Suzuki, M., Sumi, K., Koyama, H., Siqin, T., Hosoya, Takashima-Hirano, M. and Doi, H.:
   "Pd(0)-Mediated Rapid Coupling between Methyl Iodide and Hetero-Arylstannanes: an Efficient and General Method for the Incorporation of a Positron-Emitting ¹¹C Radionuclide into Heteroaromatic Frameworks"
   Chem. Eur. J., 15,12489–12495 (2009).
5. Doi, H., Ban, I., Nonoyama, A., Sumi, K., Kuang, C., Hosoya, T., Tsukada, H. and Suzuki, M.:
   "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"
   Chem. Eur. J., 15, 4165–4171 (2009).
6. Barletta, J., Karimi, F., Doi, H. and Långström, B.:
   "Synthesis of diethyl [carbonyl-¹¹C]malonate from [¹¹C]carbon monoxide by rhodium-promoted carbonylation and its application as a reaction intermediate"
   J. Label. Compd. Radiopharm. 49, 801-809 (2006).
7. Doi, H., Barletta, J., Suzuki, M., Noyori, R., Watanabe, Y. and Långström, B.:
   "Synthesis of ¹¹C-labelled N,N’-diphenylurea and ethyl phenylcarbamate by a rhodium-promoted carbonylation via [¹¹C]isocyanatobenzene using phenyl azide and [¹¹C]carbon monoxide"
   Org. Biomol. Chem., 2, 3063–3066 (2004).
8. M. Suzuki, H. Doi, Hosoya, T., Långström, B. and Watanabe, Y.:
   "Rapid methylation on carbon frameworks leading to the synthesis of a PET tracer capable of imaging a novel CNS-type prostacyclin receptor in living human brain"
   Trends Anal. Chem., 23, 595–607 (2004).
9. Suzuki, M., and Doi, H., Kato, K., Björkman, M., Långström, B., Watanabe, Y. and Noyori, R.:
   "Rapid Methylation for the Synthesis of a ¹¹C-Labeled Tolylisocarbacyclin Imaging the IP₂ Receptor in a Living Human Brain"
   Tetrahedron, 56, 8263–8273 (2000).
10. Suzuki, M., and Doi, H., Björkman, M., Andersson, Y., Långström, B., Watanabe, Y. and Noyori, R.:
    "Rapid Coupling of Methyl Iodide with Aryltributylstannanes Mediated by Palladium(0) Complexes: A General Protocol for the Synthesis of ¹¹CH₃-Labeled PET Tracers."
    Chem. Eur. J., 3, 2039–2042 (1997).