Synthesis and evaluation of [18F]FP-Lys-GE11 as a new radiolabeled peptide probe for epidermal growth factor receptor (EGFR) imaging

• DOI: 10.1016/j.nucmedbio.2020.10.004
• Publication Date: 2020-10-30T07:10:25Z
• Authors: Xueli Li; Kongzhen Hu; Wenfeng Liu; Yuanfeng Wei; Runhua Sha; Yongxuan Long; Yanjiang Han; Penhui Sun; Hubing Wu; Guiping Li; Ganghua Tang; Shun Huang
• Keywords: Fluorine Radioisotopes; Mice, Nude; Chemistry Techniques, Synthetic; 3. Good health; ErbB Receptors; Mice; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Isotope Labeling; Positron-Emission Tomography; Animals; Humans; Tissue Distribution; Peptides

The epidermal growth factor receptor (EGFR) has emerged as an attractive target in the treatment of various cancers. Radiolabeled small molecules, antibodies, and peptides that specifically target EGFR are promising probes for tumor imaging to guide personalized treatment with EGFR-targeted drugs. This study aimed to radiolabel GE11 (an EGFR-specific targeting peptide) with 18-fluorine to develop a new EGFR-targeting positron emission tomography (PET) probe, [18F]FP-Lys-GE11, for imaging tumors overexpressing EGFR.[18F]FP-Lys-GE11 was produced by radiolabeling a GE11 peptide with the prosthetic group 4-nitrophenyl-2-[18F]fluoropropionate ([18F]NFP). Stability in PBS and mice serum, affinity for A431 cell line, U87 and PC-3 cells uptake and blocking studies, and biodistribution of [18F]FP-Lys-GE11 were determined. 2 h dynamic and static PET scans of probe for tumor-bearing mice normal and inhibition uptake were performed.[18F]FP-Lys-GE11 was stable in PBS and mice serum. The Kd and Bmax values of probe for A431 were 42.43 ± 3.75 nM and 3383 ± 81.73 CPM, respectively. In cell uptake and blocking experiments, a significant reduction in radioactivity accumulation (over 4-fold) was observed by blocking U87 and PC-3 cells with unlabeled peptide. PET imaging of U87 and PC-3 tumor-bearing mice revealed clear tumor imaging (tumor radioactivity accumulation was 3.48 ± 0.44 and 3.68 ± 0.76%ID/g respectively, tumor-to-muscle ratio was 3.45 ± 0.43 and 3.64 ± 0.76 respectively). Blocking imaging revealed that the U87 tumor uptake was significantly inhibited (2.21 ± 0.41%ID/g). The biodistribution and dynamic PET imaging showed that [18F]FP-Lys-GE11 was mainly excreted by the kidneys and the rest was excreted through the bile and intestines.The current results showed that [18F]FP-Lys-GE11was a good radiolabeled peptide probe for EGFR overexpression tumor's imaging.