[11C]sorafenib: radiosynthesis and preliminary PET study of brain uptake in P-gp/Bcrp knockout mice

Chiharu Asakawa; Masanao Ogawa; Katsushi Kumata; Masayuki Fujinaga; Koichi Kato; Tomoteru Yamasaki; Joji Yui; Kazunori Kawamura; Akiko Hatori; Toshimitsu Fukumura; Ming-Rong Zhang

doi:10.1016/j.bmcl.2011.03.002

[11C]sorafenib: radiosynthesis and preliminary PET study of brain uptake in P-gp/Bcrp knockout mice

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2220-3. doi: 10.1016/j.bmcl.2011.03.002. Epub 2011 Mar 6.

Authors

Chiharu Asakawa¹, Masanao Ogawa, Katsushi Kumata, Masayuki Fujinaga, Koichi Kato, Tomoteru Yamasaki, Joji Yui, Kazunori Kawamura, Akiko Hatori, Toshimitsu Fukumura, Ming-Rong Zhang

Affiliation

¹ Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.

PMID: 21419625
DOI: 10.1016/j.bmcl.2011.03.002

Abstract

Sorafenib (Nexavar, BAY43-9006, 1) is a second-generation, orally active multikinase inhibitor that is approved for the treatment of some cancers in patients. In this Letter, we developed [(11)C]1 as a novel positron emission tomography (PET) probe, and evaluated the influence of ABC transporters-mediated efflux on brain uptake using PET with [(11)C]1 in P-glycoprotein (P-gp)/breast cancer resistance protein (Bcrp) knockout mice versus wild-type mice. [(11)C]1 was synthesized by the reaction of hydrochloride of aniline 2 with [(11)C]phosgene ([(11)C]COCl(2)) to give isocyanate [(11)C]6, followed by reaction with another aniline 3. Small-animal PET study with [(11)C]1 indicated that the radioactivity level (AUC(0-60 min), SUV×min) in the brains of P-gp/Bcrp knockout mice was about three times higher than in wild-type mice.

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / deficiency
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters / genetics
ATP-Binding Cassette Transporters / metabolism*
Animals
Benzenesulfonates / chemical synthesis
Benzenesulfonates / chemistry*
Brain / diagnostic imaging*
Carbon Radioisotopes / chemistry
Mice
Mice, Knockout
Niacinamide / analogs & derivatives
Phenylurea Compounds
Positron-Emission Tomography
Pyridines / chemical synthesis
Pyridines / chemistry*
Radiopharmaceuticals / chemical synthesis
Radiopharmaceuticals / chemistry*
Sorafenib

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters
Abcg2 protein, mouse
Benzenesulfonates
Carbon Radioisotopes
Phenylurea Compounds
Pyridines
Radiopharmaceuticals
Niacinamide
Sorafenib