Abstract
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Objectives Only a subgroup of patients receiving the mAbs against EGFR benefit from the immunotherapy, which is independent to EGFR expression level. To further clarify the antibodies delivery and localization, we performed microPET imaging in xenografts derived from three human head and neck squamous carcinoma (HNSCC) cell lines with different levels of EGFR expression.
Methods EGFR expression level in HNSCC cells were measured by flow cytomety. Nude mice bearing HNSCC tumors were imaged with microPET using 64Cu-DOTA-panitumumab. Antibody distribution among tumors was evaluated by ex vivo immunostaining. CD31 immunostaining and Evans blue assay were performed to assess tumor vascular density and permeability.
Results UM-SCC-22B tumors with the lowest EGFR expression showed the highest 64Cu-DOTA-panitumumab accumulation while SQB20 tumors with the highest EGFR expression showed the lowest 64Cu-DOTA-panitumumab accumulation. Ex vivo staining demonstrated that SQB20 cells still had extremely high EGFR expression after forming tumors. The results from CD31 immunostaining and evans blue permeability assay supported that the low vessel density, poor vascular permeability, and binding site-barrier are likely responsible for the overall low tumor uptake of the highly EGFR expressing SQB20 tumors.
Conclusions The results provide a possible explanation of the lack of observed correlation between therapeutic efficacy of cetuximab and panitumumab and EGFR expression level as determined by IHC or FISH and may shed new light in the understanding the complications of the anti-EGFR mAb therapy of HNSCC and other malignancies.
- © 2009 by Society of Nuclear Medicine