PET imaging of EGF receptors using [18F]FBEM-EGF in a head and neck squamous cell carcinoma model

Abstract

Purpose To prepare and evaluate a new radiotracer for molecular imaging of cell surface receptors for epidermal growth factor (EGF). Methods Cys-tagged EGF (cEGF) was labeled with ¹⁸F by coupling the free thiol group of the Cys tag with N-[2-(4-[¹⁸F]fluorobenzamido)ethyl]maleimide ([¹⁸F]FBEM) to form [¹⁸F]FBEM-cEGF. Cell uptake, internalization and efflux of [¹⁸F]FBEM-cEGF were tested in human head and neck squamous carcinoma UM-SCC1 cells. In vivo tumor targeting and pharmacokinetics of the radiotracers were evaluated in UM-SCC1 tumor-bearing athymic nude mice by static and dynamic microPET imaging. Ex vivo biodistribution assays were performed to confirm the noninvasive imaging results. Results The radiolabeling yield for [¹⁸F]FBEM-cEGF was over 60%, based on starting [¹⁸F]FBEM. [¹⁸F]FBEM-cEGF exhibited rapid blood clearance through both hepatobiliary and renal excretion. UM-SCC1 tumors were clearly visualized and showed modest tracer uptake of 2.60 ± 0.59 %ID/g at 30 min after injection. Significantly higher tumor uptake of [¹⁸F]FBEM-cEGF (5.99 ± 1.61%ID/g at 30 min after injection, p < 0.01) and tumor/nontumor ratio were achieved by coinjection of 50 μg of unlabeled EGF. Decreased liver uptake of [¹⁸F]FBEM-cEGF was observed when unlabeled EGF was coadministered. Conclusion With optimized liver blocking, [¹⁸F]FBEM-cEGF has the potential to be used in a noninvasive and quantitative manner for detection of malignant lesions and evaluation of EGFR activity.