Pharmacokinetic analysis of 6-O-[18F]FEE for PET imaging of EGFR mutation

Abstract

6-O-[18F]Fluoroethylerlotinib (6-O-[18F]FEE), with a suitable half-life for commercial distribution, may be a good replacement for [11C]erlotinib to identify epidermal growth factor receptor (EGFR) positive tumors with activating mutations to tyrosine kinase inhibitors therapy. In this study, we explored the fully automated synthesis of 6-O-[18F]FEE and investigated its pharmacokinetics in tumor-bearing mice. 6-O-[18F]FEE with high specific activity (28–100 GBq/μmol) and radiochemistry purity (over 99 %) was obtained by two-step reaction and Radio-HPLC separation in PET-MF-2 V-IT-1 automated synthesizer. PET imaging of 6-O-[18F]FEE in HCC827, A431, and U87 tumor-bearing mice with different EGFR expression and mutation was performed. Uptake and blocking of PET imaging indicated that the probe specifically targeted exon 19 deleted EGFR (the quantitative analysis of tumor-to-mouse ratio for HCC827, HCC827 blocking, U87, A431 was 2.58 ± 0.24, 1.20 ± 0.15, 1.18 ± 0.19, and 1.05 ± 0.13 respectively). Dynamic imaging was used to study the pharmacokinetics of the probe in tumor-bearing mice. Logan plot graphical analysis demonstrated late linearity and a high fitting correlation coefficient (0.998), supporting reversible kinetics. According to the Akaike Information Criterion (AIC) rule, the 2-compartment reversible model was more consistent with the metabolic properties of 6-O-[18F]FEE. The automated radiosynthesis and pharmacokinetic analysis will promote clinically transformation of 6-O-[18F]FEE.