Diagnosis and Radioimmunotherapy of Head and Neck Squamous Cell Carcinomas

• Main Author: Ekberg, Tomas
• Format: Doctoral Thesis
• Language: English
• Published: Uppsala universitet, Öron-, näs- och halssjukdomar 2008
• Subjects: Otorhinolaryngology; head and neck squamous cell carcinoma; tumor targeting; radionuclide targeting; PET; therapy; diagnistics; antibodies; Otorhinolaryngologi
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8395; http://nbn-resolving.de/urn:isbn:978-91-554-7060-9

The diagnosis and treatment of patients with advanced tumors in the head and neck is an interesting challenge where there is a need for new approaches in diagnostics and adjuvant treatment. Differences in antigen expression between tumors and normal tissues provide a means for application of antibody-based targeting techniques. By targeting a structure that is abundant on tumor cells and limited on normal cells, radioactivity can be delivered. The use of positron emission tomography (PET) in patients with head and neck tumors is evaluated in this thesis. PET using the tracer fluorodeoxyglucose (FDG) is found to play an important diagnostic role and often has a direct clinical impact on planned surgery or other treatment. Possible targeting structures are also investigated in this thesis, and it is concluded that the EGFR and CD44v6 stand out as possible antigens for targeting approaches of squamous cell carcinomas in the head and neck (HNSCC). A radioimmunoassay for quantification of EGFR and CD44v6 is validated and concluded to be a valuable complement to immunohistochemistry for the analysis of tumors and for the planning of radioimmunotherapy. Finally, promising results of radioimmunotherapy in tumor bearing mice with the monoclonal antibody U36 labeled with the alpha emitter astatine-211 are presented. These results demonstrate how differences between tumors and normal tissues can be used to improve diagnostic outcomes and indicate that radioimmunotherapy can be a future adjuvant therapy or treatment of residual disease in HNSCC.