PET Imaging in Head and Neck Cancer Patients to Monitor Treatment Response: A Future Role for EGFR-Targeted Imaging

Abstract

Approximately 50,000 new cases of head and neck squamous cell carcinoma (HNSCC) are diagnosed worldwide each year and subsequently treated with surgery, chemotherapy, radiotherapy, and/or targeted therapy. The heterogeneity of the patient population in terms of treatment response drives the search for tumorspecific biomarkers. Imaging of biomarkers can reveal patientspecific responses to therapies and, if assessed early after the start of treatment, may allow adaptation of treatment regimens. In this review, tracers that have been tested to monitor treatment efficacy in HNSCC by PET scanning prior to and early after the onset of treatment are discussed. An important imaging target for this application in HNSCC patients is the EGFR. It steers the pathways related to proliferation, hypoxia, DNA damage repair, and apoptosis, all treatment-resistance mechanisms. The anti-EGFR antibody cetuximab has been labeled with various radionuclides and has been tested as an imaging biomarker in several HNSCC models. These studies suggest that EGFR-targeting tracers can be used to monitor EGFR receptor expression in HNSCC and have the potential to noninvasively monitor cetuximab treatment and steer individualized treatment regimens. Multiple factors can influence the uptake of EGFR-targeting tracers. Here, we discuss the relevance of gene and protein overexpression, mutations, and amplifications related to EGFR signaling. In addition, monoclonal antibody properties and the effect on the host immune system are reviewed in light of the future role of EGFR-targeted imaging in HNSCC.

Multimodal Imaging of Head and Neck Squamous Cell Carcinoma

“…42 There is an increasing assortment of radiotracers targeting alternate pathways (fluorothymidine F 18, cellular proliferation), receptor targets, and tumor environmental conditions (fluoromisonidazole F 18, tumor hypoxia) that may prove useful for further characterizing HNSCC in patients. [43][44][45]…”

Anti-EGFR Therapy: Strategies in Head and Neck Squamous Cell Carcinoma

“…The role of EGFR traffic has been associated with HNSCC resistance to multimodal therapy. The use of radiolabeled EGFR-inhibitors may be an efficient tool to monitor clinical response [85].…”

Tumor Volumes and Prognosis in Laryngeal Cancer

“…A significant impact of the delineation of GTV P ’s in laryngeal SCC translated into more normal tissue sparing after conformal radiotherapy planning. Others have demonstrated the ability of anti-EGFR (cetuximab) radiolabeled tracers with PET scans to monitor receptor expression in Head and Neck cancers [ 85 ]. Tumor Hypoxic index, given the established relationship between hypoxia and radiotherapy treatment resistance, is another factor that has been studied in patients with laryngeal cancers.…”