PET imaging of EGFR-positive tumors using an ¹⁸F-labeled peptide

Objectives: Epidermal growth factor receptor (EGFR) was an attractive biomarker for the diagnosis, prognosis and therapy of the related cancer because of it has been demonstrated worldwide overexpressed on malignant tumors, including cancers of the non-small cell lung, breast, renal, ovarian, colon, glioma, pancreatic, bladder, and head and neck ^[1,2]. GE11 (Tyr-His-Trp-Tyr-Gly-Tyr-Thr-Pro-Gln-Asn-Val-Ile) was an EGFR-specific peptide (kd = 22 nM) developed by Li (2005) with screening a phage display library with human EGFR (hEGFR) ^[3]. The aim of this study was to develop ¹⁸F-labelled GE11 as a PET tracer for targeting EGFR imaging.

Methods: The prosthetic group of 4-nitrophenyl-2-¹⁸F-fluoropropionate (¹⁸F-NFP) was introduced to the side chain of added Lysine at GE11’s N terminus (figure 1 A). The partition coefficients, stability in vitro, and metabolic stability of ¹⁸F-FP-Lys-GE11 were carried out. Biodistribution studies were carried out in normal BALB/c mice at 60 min to evaluate the pharmacokinetics of probe. PET imaging of ¹⁸F-FP-Lys-GE11 was performed in U87 tumor bearing models with positive EGFR.

Results: ¹⁸F-FP-Lys-GE11 can be produced in 120 min with decay corrected yield of 7 ± 4% (n = 6), radiochemical purity of 99% and specific activity of 50-100 GBq/µmol. The LogP value of ¹⁸F-FP-Lys-GE11 was -2.09 ± 0.05 (n = 4). The probe was stable in PBS solution. But there was a decomposed peak (27.8% of all radioactivity) at 7 min of the HPLC chromatogram in serum. The biodistribution data of 60 min postinjection revealed that ¹⁸F-FP-Lys-GE11 exhibited rapid blood clearance through renal excretion. The tumor uptake of ¹⁸F-FP-Lys-GE11 in U87 tumor xenografts was visualized in PET image (figure 1 B). Time-activity curves of main organs and tissues from dynamic PET imaging were consistent with the biodistribution data (figure 1 C). The percent of the total injected dose per gram of tissue (%ID/g) of U87 tumor at 2 h postinjection reached 2.5 ± 0.28 (the max of % ID/g was 4.15). Conclusions: Our results demonstrate the potential of using ⁸F-FP-Lys-GE11 as a PET agent for molecular imaging of EGFR-positive tumors.

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