c-Met is a receptor tyrosine kinase shown inappropriate expression and actively involved in progression and metastasis in most types of human cancer. Development of c-Met-targeted imaging and therapeutic agents would be extremely useful

Previous studies reported that c-Met-binding peptide (Met-pep1, YLFSVHWPPLKA) specifically targets c-Met receptor. Here, we evaluated 18F-labeled Met-pep1 for PET imaging of c-Met positive tumor in human head and neck squamous cell carcinoma (HNSCC) xenografted mice.

Fluorine-18 [18F] is one of the most widely used positron emission isotopes for PET imaging because it has good imaging characteristics and ideally suited half-life (about 110 min) for the small-molecular-weight peptides. So far, in a majority of cases, peptide labeling is achieved by using 18F-containing prosthetic groups.

However, 18F has not been used for the labeling of the Met-pep1 peptide for in vivo PET imaging in HNSCC model. Here, we have labeled the c-Met peptide (Met-pep1) with [18F]-NPFP and further evaluated the in vitro cell uptake, internalization, and efflux studies on UM-SCC-22B cells and in vivo distribution pattern and c-Met-targeting efficacy using microPET imaging in HNSCC xenograft-bearing mice

c-Met-binding peptide, Met-pep1, was synthesized and labeled with 4-nitrophenyl [18F]-2-fluoropropionate ([18F]-NPFP) ([18F]FP-Met-pep1). The cell uptake, internalization, and efflux of [18F]FP-Met-pep1 were assessed in UM-SCC-22B cells. In vivo pharmacokinetics, blocking and biodistribution of the radiotracers were investigated in tumor-bearing nude mice by microPET imaging.

Results

The radiolabeling yield for [18F]FP-Met-pep1 was over 55% with 97% purity. [18F]FP-Met-pep1 showed high tumor uptake in UM-SCC-22B tumor-bearing mice with clear visualization.

The specificity of the imaging tracer was confirmed by significantly decreased tumor uptake after co-administration of unlabeled Met-pep1 peptides. Prominent uptake and rapid excretion of [18F]FP-Met-pep1 was also observed in the kidney, suggesting this tracer is mainly excreted through the renal-urinary routes. Ex vivo biodistribution showed similar results that were consistent with microPET imaging data.

These results suggest that 18F-labeled c-Met peptide may potentially be used for imaging c-Met positive HNSCC cancer in vivo and for c-Met-targeted cancer therapy.