Molecular Imaging Labeling Chemistry Laboratory
Team Leader
Hisashi DOI (D.Sci.)
Our laboratory is, in cooperation with the Molecular Imaging Medicinal Chemistry Laboratory, working to develop PET probe syntheses for medical biomarkers and drug candidates, and realize novel chemical labeling reactions with the aim of broadening the spectrum of potential applications of organic chemistry in life science research. As one of our main projects, we are striving toward introducing 11C into carbon frameworks of bioactive organic compounds by developing rapid C-[11C]methylation reactions based on the carbon-carbon bond formation, focusing on the methyl group as the minimum carbon substituent. We have already succeeded in developing several cross-coupling reactions between organotin or organoboron compounds and [11C]methyl iodide in the presence of palladium(0) catalysts. These reactions are attracting worldwide attention as groundbreaking synthesis for introducing the [11C]methyl group into a carbon framework in the very short time of 5 minutes.
- Development of the PET probes syntheses of drug candidates and the novel labeling reactions
- Development of the remote-comtorolled synthesizers and the efficient synthetic procedures for radiolabeling by organometallic chemistry
- Establishment of the general methodologies for high-quality synthesis of PET probes applicabel to human clinical study
- March 9,2010
- Labeling of antipyretic and analgesic drugs enables successful visualization inside the body
- M. Suzuki, M. Takashima-Hirano, H. Koyama, T. Yamaoka, K. Sumi, H. Nagata, H. Hidaka, H. Doi.:
"Efficient synthesis of [11C]H-1152, a PET probe specific for Rho-kinases, highly potential targets in diagnostic medicine and drug development"
Tetrahedron 68, 2336-2341 (2012) - T. Kuboyama, M. Nakahara, M. Yoshino, Y. Cui, T. Sako, Y. Wada, T. Imanishi, S. Obika, Y. Watanabe, M. Suzuki, H. Doi.:
"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) - M. Suzuki, H. Doi.:
"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) - M. Takashima-Hirano, M. Shukuri, T. Takashima, M. Goto, Y. Wada, Y. Watanabe, H. Onoe, H. Doi, M. Suzuki.:
"General Method for 11C-Labeling of 2-Arylpropionic Acids and Their Esters: Construction of a PET Tracer Library for a Study of Biological Events Involved in COXs Expression"
Chem. Eur. J, 16, 4250-4258 (2010) - M. Suzuki, K. Sumi, H. Koyama, Siqin, T. Hosoya, M. Takashima-Hirano, H. Doi.:
"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) - H. Doi, I. Ban, A. Nonoyama, K. Sumi, C. Kuang, T. Hosoya, H. Tsukada, M. Suzuki.:
"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) - J. Barletta, F. Karimi, H. Doi, B. Långström.:
"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) - T. Hosoya, K. Sumi, H. Doi, M. Wakao, and M. Suzuki.:
"Rapid methylation on carbon frameworks useful for the synthesis of 11CH3-incorporated PET tracers: Pd(0)-mediated rapid coupling of methyl iodide with an alkenyltributylstannane leading to a 1-methylalkene"
Org. Biomol. Chem., 4, 410-415 (2006) - H. Doi, J. Barletta, M. Suzuki, R. Noyori, Y. Watanabe, B. Långström.:
"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) - M. Suzuki, H. Doi, T. Hosoya, B. Långström, Y. Watanabe.:
"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)
Principal Investigator
- Hisashi DOI
- Team Leader
Members
- Miki GOTO
- Research Associate
- Tatsuya KIDA
- Research Associate
- Tomoko MORI
- Technical Staff I
- Sachi KURAI
- Technical Staff I
- Ami ANDO
- Technical Staff I