Panitumumab was also labeled with a longer half lived PET i

Nevertheless, the pharma cokinetics of 64Cu DOTA cetuximab was characteristic of antibodies and displayed very slow clearance from non target organs such as the blood, spleen, heart, lung, and liver. At 24 hour postinjection these organs still had high uptake, suggesting that optimal contrast might be observed at late time points. A more potent KU-55933 臨床試験 monoclonal antibody of the EGFR, panitumumab, approved for the treatment of colorectal cancer by the FDA, was conjugated with DOTA and labeled with 64Cu. The ability of 64Cu DOTA panitumumab to image EGFR expression levels was tested in three human head and neck squamous cell carcinoma cell lines, which had different levels of EGFR expression, determined by flow cytometry in the order of UM SCC 22B, SAS, SQB20.<br><br> Interestingly, there was no correlation between PET quantification buy Linifanib and EGFR protein expression level. The tumor cell lines that had the lowest EGFR protein expression among the three cell lines tested, showed the highest accumulation of 64Cu DOTA panitumumab, whereas the tumor cell line with the highest EGFR expression showed the lowest accumu lation of 64Cu DOTA panitumumab. The tumors were excised and immunofluorescence staining was performed to determine EGFR expression in the tumors ex vivo. EGFR expression was found to be correlated with the flow cytometry results. However, after in vivo injection of fluorescein isothiocyanate labeled panitumumab, the staining profile was signifi cantly different, whereas UM SCC 22B had uniform staining, SQB20 slides had patchy staining, suggesting distant metastatic lesion sites.<br><br> 89Zr Panitumumab accumulated in positive tumors with a peak tumor uptake of 42. 89 6 4. 49%IDg 3 days LY3009104 1187594-09-7 postinjection and was proven to be specific to EGFR by blocking with unlabeled panitumumab. Another biomarker for targeting EGFR is anti EGFR Affibody protein, which has been site specifically labeled with 18F and 64Cu and evaluated in tumor bearing mice. The labeled Affibody molecule showed good pharmacoki netics in vivo with fast accumulation in EGFR positive tumors but also displayed very high uptake in the liver. 64Cu Affibody also had extremely high renal uptake and retention, although this issue was partially resolved by 18F labeling. Sur prisingly, liver uptake was reduced and tumor uptake was increased when the labeled Affibody was admin low penetration of the antibody in the SQB20 tumors.<br><br> In an attempt to explain these results, the vascularity of each tumor type was examined, and it turned out that the microvascular density of SQB20 was the lowest. The researchers suggested that the vascular density can be a determining factor for antibody dif fusion and binding and subsequently influence treatment efficacy. To ensure their idea, the researchers re peated the experiment with another antibody tracer, 64 Cu DOTA cetuximab, that showed similar results to those obtained with 64Cu DOTA panitumumab in this model of HNSCC. Similar disparity results were also shown by Aerts et al. using 89 Zr Cetuximab. This study provides evidence for the lack of an observed correlation between therapeutic efficacy of cetuximab and panitumumab and EGFR expression level as determined by immunohistochemistry and emphasizes the superiority of PET imaging for de termining drug accumulation in target organ.