Synthesis and Biological Evaluation of an 18Fluorine-Labeled COX Inhibitor—[18F]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 Ts 2 O, 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.

Synthesis of para‐[18F]Fluorofenbufen Octylamide for PET Imaging of Brain Tumors

“…The nonpolar metabolite is suggested to be some aliphatic modification on the amido group, thus lowering the polarity. Stability of FFOA has been significantly improved in comparison with FOFA in view of the longer t 1/2 (> 30 min vs. <5 min) …”

“…Based on this concept, in this study, we modify the structure of octyl fenbufen amide (OFA) for improving its bioactivity profile . Whereas [ 123 I]IFOA, an analog of OFA, has been used to image liver cancer, such as cholangiocarcinoma, its limited aqueous solubility deters its further in vivo use.…”

“…Whereas [ 123 I]IFOA, an analog of OFA, has been used to image liver cancer, such as cholangiocarcinoma, its limited aqueous solubility deters its further in vivo use. Fluoro substitution on the terminal end of the aliphatic chain to give fluorooctyl fenbufen amide (FOFA) not only improves its aqueous solubility but also enhances its blood–brain barrier (BBB) penetration and tumor targeting . However, the in vivo instability due to defluorination from the sp 3 C─F bond needs to be improved.…”

Nonsteroidal Anti-Inflammatory Drug Conjugated with Gadolinium (III) Complex as an Anti-Inflammatory MRI Agent

“…Moreover, there have been several attempts to realize targeted imaging of inflammation using inflammatory mediators as imaging biomarkers [ 14 , 22 , 23 , 24 , 25 , 26 , 27 ]. Of these targeted imaging techniques, magnetic resonance imaging (MRI) has demonstrated several advantages to investigate the human anatomy and physiology with superior spatial resolution.…”