Predictive efficacy of 11C-PD153035 PET imaging for EGFR–tyrosine kinase inhibitor sensitivity in non-small cell lung cancer patients

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Abstract

To determine the correlation of 11C-PD153035 uptake with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sensitivity and phosphorylated EGFR (pEGFR) expression in non-small cell lung cancer (NSCLC) cell lines with different EGFR-TKI sensitivities and in their corresponding xenografts. Four human NSCLC cell lines (HCC827, PC9, A549, and H1975) in the logarithmic phase were co-incubated with 11C-PD153035 to analyze the correlation of 11C-PD153035 uptake with EGFR-TKI sensitivity, and EGFR/pEGFR expression. Nude mice xenograft models bearing the four NSCLCs were prepared. 11C-PD153035 positron-emission tomography (PET)-computed tomography (CT) was used to image the xenografts and observe radioactive uptakes. Correlation of the in vivo uptakes with EGFR-TKI sensitivity, and EGFR/pEGFR expression was analyzed. HCC827 and PC9 cells, which were highly sensitive to EGFR-TKIs, exhibited higher 11C-PD153035 uptakes than the other cells. A549 cells, which were moderately sensitive to EGFR-TKIs, showed higher uptake than the EGFR-TKI–resistant H1975 cells, which showed little or no uptake. Radioactive uptakes were positively correlated with pEGFR expression in all cells. PET-CT showed that radioactivity was highest in HCC827 xenografts. The radioactivity in PC9 xenografts was higher than that in A549 and H1975 xenografts. Tumor vs. non-tumor tissue ratio values were positively correlated with pEGFR expression in HCC827 and PC9 xenografts, but not in A549 and H1975 xenografts. In conclusion, 11C-PD153035 can serve as an EGFR imaging agent in vitro and in vivo, and predicts sensitivity to EGFR-TKIs. This will provide an experimental basis for clinical applications of 11C-PD153035 and individualized NSCLC therapy.

What's new?

This study indicated that 11C-PD153035 can serve as an EGFR imaging agent in vitro and in vivo, and predicts sensitivity to EGFR-TKIs through the determination of the correlation of 11C-PD153035 uptake with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sensitivity and phosphorylated EGFR (pEGFR) expression in NSCLC cell lines and in their corresponding xenografts with different EGFR-TKI sensitivities. This will provide an experimental basis for clinical applications of 11C-PD153035 PET imaging and individualized NSCLC therapy.

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