title: Synthesis and Biological Evaluation of an (18)Fluorine-Labeled COX Inhibitor--[(18)F]Fluorooctyl Fenbufen Amide--For Imaging of Brain Tumors.
abstract: Molecular imaging of brain tumors remains a great challenge, despite the advances made in imaging technology. An anti-inflammatory compound may be a useful tool for this purpose because there is evidence of inflammatory processes in brain tumor micro-environments. Fluorooctylfenbufen amide (FOFA) was prepared from 8-chlorooctanol via treatment with potassium phthalimide, tosylation with Ts2O, fluorination with KF under phase transfer catalyzed conditions, deprotection using aqueous hydrazine, and coupling with fenbufen. The corresponding radiofluoro product [(18)F]FOFA, had a final radiochemical yield of 2.81 mCi and was prepared from activated [(18)F]F(-) (212 mCi) via HPLC purification and concentration. The radiochemical purity was determined to be 99%, and the specific activity was shown to exceed 22 GBq/μmol (EOS) based on decay-corrected calculations. Ex-vivo analysis of [(18)F]FOFA in plasma using HPLC showed that the agent had a half-life of 15 min. PET scanning showed significant accumulation of [(18)F]FOFA over tumor loci with reasonable contrast in C6-glioma bearing rats. These results suggest that this molecule is a promising agent for the visualization of brain tumors. Further investigations should focus on tumor micro-environments.
authors.affiliation: Department of Neurosurgery, Chang-Gung Memorial Hospital at Chiayi and Chang Gung University, Taoyuan 33302, Taiwan. ns3068@gmail.com.
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsinghua University, Hsinchu 300, Taiwan. flyinken0221@hotmail.com.
authors.forename: Yu-Chia
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Surgery, Chang-Gung Memorial Hospital at Linkou and Chang Gung University, Guei-shan 33305,Taiwan. yehchunnan@gmail.com.
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Yeh
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsinghua University, Hsinchu 300, Taiwan. csyu@mx.nthu.edu.tw.|Institute of Nuclear Engineering and Science, National Tsing-Hua University, Hsinchu 300, Taiwan. csyu@mx.nthu.edu.tw.
authors.forename: Chung-Shan
authors.initials: CS
authors.lastname: Yu
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes / Q000008:administration & dosage / Q000737:chemistry; D005910:Glioma / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D007553:Isotope Labeling; D010654:Phenylbutyrates / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000737:chemistry; D049268:Positron-Emission Tomography; D051381:Rats
chemical_list: D005462:Fluorine Radioisotopes; D010654:Phenylbutyrates; C010725:fenbufen
keywords: Inflammation; NSAIDs; cyclooxygenase; molecular imaging