[11C]Gefitinib ([11C]Iressa): Radiosynthesis, In Vitro Uptake, and In Vivo Imaging of Intact Murine Fibrosarcoma

摘要: 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 [11C]gefitinib to explore its specific binding in intact fibrosarcoma (NFSa)-bearing mice. [11C]Gefitinib was synthesized by the reaction of desmethyl precursor (1) [11C]CH3I. vitro uptake into NFSa, human-A431 epidermoid carcinoma, Jurkat T cells determined. Positron emission tomography (PET) imaging using performed for NFSa-bearing accumulated NFSa 2.1 ratio (UR)/mg protein cells. Addition nonradioactive decreased a concentration-dependent manner. also had high (2.6 UR/mg protein) epidermal growth factor receptor/tyrosine kinase (EGFR/TK)-rich A431 but low (0.2 EGFR/TK-poor vivo distribution study on mice dissection method revealed that specifically tumor. The radioactivity tumors blood muscle as two comparative regions increased from 0.4 6.0 0.6 5.0 during experiment (0–60 min), respectively. PET produced clear tumor image, although distributed throughout body. Treatment (100 mg/kg) metabolite analysis demonstrated stable tumor, liver, kidney, blood. These results promising potential serve ligand