RRC ID 38274
著者 Zhang MR, Kumata K, Hatori A, Takai N, Toyohara J, Yamasaki T, Yanamoto K, Yui J, Kawamura K, Koike S, Ando K, Suzuki K.
タイトル [11C]Gefitinib ([11c]Iressa): radiosynthesis, in vitro uptake, and in vivo imaging of intact murine fibrosarcoma.
ジャーナル Mol Imaging Biol
Abstract OBJECTIVE:Gefitinib (N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine, Iressa) is an approved anticancer drug. In this study, we labeled gefitinib with carbon-11 and evaluated [(11)C]gefitinib to explore its specific binding in intact fibrosarcoma (NFSa)-bearing mice.
METHODS:[(11)C]Gefitinib was synthesized by the reaction of desmethyl precursor (1) with [(11)C]CH(3)I. In vitro uptake of [(11)C]gefitinib into NFSa, human-A431 epidermoid carcinoma, and Jurkat T cells was determined. Positron emission tomography (PET) imaging using [(11)C]gefitinib was performed for NFSa-bearing mice.
RESULTS:[(11)C]Gefitinib accumulated into NFSa cells with 2.1 uptake ratio (UR)/mg protein in cells. Addition of nonradioactive gefitinib decreased uptake in a concentration-dependent manner. [(11)C]Gefitinib also had high uptake (2.6 UR/mg protein) into epidermal growth factor receptor/tyrosine kinase (EGFR/TK)-rich A431 cells but low uptake (0.2 UR/mg protein) into EGFR/TK-poor Jurkat cells. In vivo distribution study on NFSa-bearing mice by the dissection method revealed that [(11)C]gefitinib specifically accumulated into the tumor. The ratio of radioactivity in tumors to that in blood and muscle as two comparative regions increased from 0.4 to 6.0 and from 0.6 to 5.0 during this experiment (0-60 min), respectively. PET for NFSa-bearing mice produced a clear tumor image, although high radioactivity was distributed throughout the body. Treatment with nonradioactive gefitinib (100 mg/kg) decreased uptake in the tumor. In vivo metabolite analysis demonstrated that [(11)C]gefitinib was stable in the tumor, liver, kidney, and blood.
CONCLUSION:These results demonstrated the promising potential of [(11)C]gefitinib to serve as a PET ligand for in vivo imaging of NFSa-bearing mice.
巻・号 12(2)
ページ 181-91
公開日 2010-4-1
DOI 10.1007/s11307-009-0265-5
PMID 19784702
MeSH Animals Carbon Radioisotopes Cell Line, Tumor Fibrosarcoma / diagnostic imaging* Gefitinib Humans Male Mice Molecular Imaging / methods* Positron-Emission Tomography Quinazolines / chemical synthesis* Quinazolines / chemistry Quinazolines / pharmacokinetics Tissue Distribution
IF 2.925
引用数 41
WOS 分野 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
リソース情報
ヒト・動物細胞