(18)F-labeled FGFR1 peptide: a new PET probe for subtype FGFR1 receptor imaging

INTRODUCTION: The fibroblast growth factor receptor (FGFR) family is highly expressed in a variety of tumor types and represents a new target for cancer therapy. Different FGFR subtype aberrations have been found to exhibit highly variable sensitivity and efficacy to FGFR inhibitors. METHODS: The present study is the first to suggest an imaging method for assessing FGFR1 expression. The FGFR1-targeting peptide NOTA-PEG2-KAEWKSLGEEAWHSK was synthesized by manual solid-phase peptide synthesis and high-pressure liquid chromatography (HPLC) purification and then labeled with fluorine-18 using NOTA as a chelator. In vitro and in vivo experiments were conducted to evaluate the stability, affinity and specificity of the probe. Tumor targeting efficacy and biodistribution were evaluated by micro-PET/CT imaging in RT-112, A549, SNU-16 and Calu-3 xenografts. RESULTS: The radiochemical purity of [18F]F-FGFR1 was 98.66% ± 0.30% (n = 3) with excellent stability. The cellular uptake rate of [18F]F-FGFR1 in the RT-112 cell line (FGFR1 overexpression) was higher than that in the other cell lines and could be blocked by the presence of excess unlabeled FGFR1 peptide. Micro-PET/CT imaging revealed a significant concentration of [18F]F-FGFR1 in RT-112 xenografts with no or very low uptake in nontargeted organs and tissues, which demonstrated that [18F]F-FGFR1 was selectively taken up by FGFR1-positive tumors. CONCLUSION: [18F]F-FGFR1 showed high stability, affinity, specificity and good imaging capacity for FGFR1-overexpressing tumors in vivo, which provides new application potential in the visualization of FGFR1 expression in solid tumors.