Year: 2024
Type: article
Abstract: In head and neck squamous cell carcinoma (HNSCC), the mesenchymal epithelial transition (MET) receptor drives cancer growth, proliferation, and metastasis. MET is known to be overexpressed in HNSCC and, therefore, is an appealing therapeutic target. In this study, we evaluated MET expression in patients with HNSCC and investigated the potential imaging application of a novel MET-binding single-domain camelid antibody using positron emission tomography/computed tomography (PET/CT) in a preclinical MET-expressing HNSCC model. Multiplex immunostaining for MET protein performed on a tissue microarray from 203 patients with HNSCC found 86% of patients to have MET expression, with 14% having high expression and 53% having low MET expression. Using The Cancer Genome Atlas (TCGA) database, high MET RNA expression was associated with worse progression-free survival and overall survival in patients with HPV-negative HSNCC. Utilizing flow cytometry and immunofluorescence, our novel camelid antibody fused to a human IgG Fc chain (1E7-Fc) showed high binding affinity and specificity to high MET-expressing Detroit 562 cells but not to low MET-expressing HNSCC cells. The efficacy and biodistribution of [ 89 Zr]Zr-1E7-Fc as a PET imaging agent was then investigated in a MET-expressing head and neck xenograft model. [ 89 Zr]Zr-1E7-Fc rapidly localized and showed high tumor uptake in Detroit 562 xenografts (8.4% ID/g at 72 h postinjection), with rapid clearance from the circulatory system (2.7 tumor-to-blood radioactivity ratio at 72 h postinjection). Our preclinical data suggest that the camelid antibody 1E7-Fc could be a potential theranostic agent for HNSCC. Further investigations are warranted to confirm these findings in patients and to evaluate 1E7-Fc as an imaging agent and platform to deliver radionuclide or drug therapy to MET-driven cancers.
Source: Molecular Pharmaceutics
Authors: Rachel L. Minne, Natalie Y. Luo, Caroline M. Mork, Madalynn R. Wopat, Karla Esbona, Saahil Javeri, Kwangok P. Nickel, Reinier Hernandez, Aaron M. LeBeau, Randall J. Kimple, Andrew M. Baschnagel
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G115506582, Novel Radioimmunotherapy Strategies for Prostate Cancer, G4004214011, G42679306, G4319453063, Head and Neck Cancer SPORE at the University of Wisconsin, Institutional Clinical and Translational Science Award (UW-Madison), Targeting CD133 for imaging and therapy in prostate cancer, G9000265189, University of Wisconsin Institute for Clinical and Translational Research, Improving the translational value of head and neck cancer patient-in-mouse models
OpenAlex ID: W4404186897