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• W1977703188 abstract "The epidermal growth factor receptor (EGFR) is highly expressed in a significant number of human malignancies, and its expression is associated with tumor aggressiveness and overall treatment resistance. The monoclonal antibody cetuximab is increasingly used in clinical settings as a treatment modality in combination with more conventional therapies, such as radio- and chemotherapy. Currently, little is known about tumor-specific uptake and overall pharmacokinetics. Noninvasive quantification of cetuximab uptake could provide important diagnostic information for patient selection and therapy evaluation. To this end, we have developed and validated a novel probe using cetuximab labeled with the long-lived positron emitter 89Zr for PET imaging.Tumor cell lines with varying EGFR expression levels were used for in vivo tumor imaging experiments. PET with 89Zr-labeled cetuximab (3.75+/-0.14 MBq) was performed on tumor-bearing NMRI-nu mice at multiple time points after injection (ranging from 1 to 120 h) and quantified by drawing regions of interest on selected tissues. Uptake was compared by biodistribution gamma-counting, and ex vivo EGFR expression levels were quantified using Western blot analysis.Uptake of 89Zr-labeled cetuximab was demonstrated in the EGFR-positive tumors. However, the EGFR levels measured in vivo did not correlate with the relative signal obtained by PET. Tumor-to-blood ratios were significantly higher in the cell lines with intermediate (compared with the high) EGFR expression starting from 24 h after injection. Normal tissue uptake was unaffected by the different tumor types. Ex vivo gamma-counting experiments confirmed the observed in vivo PET results. A similar disparity was found between 89Zr-labeled cetuximab tumor uptake and in vivo EGFR expression levels as demonstrated by Western blotting.The 89Zr-labeled cetuximab imaging probe is a promising tool for noninvasive evaluation of cetuximab uptake. Our results demonstrate a disparity between in vivo EGFR expression levels and cetuximab uptake. In a general sense, the results indicate a disparity between antibody uptake and expression levels of a biologic target in a tumor, suggesting that additional pharmacokinetic or pharmacodynamic mechanisms influence tumor delivery of this therapy. These additional mechanisms may explain why receptor expression levels alone are not sufficient to predict patient response." @default.
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• W1977703188 date "2008-12-17" @default.
• W1977703188 modified "2023-09-25" @default.
• W1977703188 title "Disparity Between In Vivo EGFR Expression and ⁸⁹Zr-Labeled Cetuximab Uptake Assessed with PET" @default.
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• W1977703188 doi "https://doi.org/10.2967/jnumed.108.054312" @default.
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