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

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Fibroblast growth factor receptor (FGFR) family is highly expressed in various tumors, making it a promising cancer therapy target.
• FGFR subtype aberrations influence sensitivity and efficacy of FGFR inhibitors, highlighting the need for targeted therapies.

Purpose of the Study:

• To develop and evaluate a novel imaging method for assessing fibroblast growth factor receptor 1 (FGFR1) expression.
• To synthesize and characterize a fluorine-18 labeled peptide probe targeting FGFR1 for molecular imaging applications.

Main Methods:

• Synthesized and purified a FGFR1-targeting peptide (NOTA-PEG2-KAEWKSLGEEAWHSK) using solid-phase peptide synthesis and HPLC.
• Labeled the peptide with fluorine-18 using NOTA as a chelator to create the [18F]F-FGFR1 probe.
• Evaluated probe stability, affinity, specificity, tumor targeting efficacy, and biodistribution using in vitro assays and micro-PET/CT imaging in various xenografts.

Main Results:

• [18F]F-FGFR1 exhibited high radiochemical purity (98.66% ± 0.30%) and excellent stability.
• The probe showed significantly higher cellular uptake in FGFR1-overexpressing RT-112 cells, which was blocked by excess unlabeled peptide.
• Micro-PET/CT imaging confirmed selective and significant uptake of [18F]F-FGFR1 in FGFR1-positive RT-112 xenografts with minimal uptake in non-targeted tissues.

Conclusions:

• [18F]F-FGFR1 possesses high stability, affinity, and specificity for FGFR1.
• The probe demonstrates effective in vivo imaging capacity for FGFR1-overexpressing tumors.
• This novel radiotracer holds potential for visualizing FGFR1 expression in solid tumors, aiding in targeted cancer therapy.