Predictive efficacy of 11 C‐PD153035 PET imaging for EGFR–tyrosine kinase inhibitor sensitivity in non‐small cell lung cancer patients
To determine the correlation of 11 C‐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 xen...
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Published in | International journal of cancer Vol. 138; no. 4; pp. 1003 - 1012 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
15.02.2016
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Online Access | Get full text |
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Summary: | To determine the correlation of
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C‐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
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C‐PD153035 to analyze the correlation of
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C‐PD153035 uptake with EGFR‐TKI sensitivity, and EGFR/pEGFR expression. Nude mice xenograft models bearing the four NSCLCs were prepared.
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C‐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
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C‐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,
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C‐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
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C‐PD153035 and individualized NSCLC therapy.
What's new?
This study indicated that
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C‐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
11
C‐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
11
C‐PD153035 PET imaging and individualized NSCLC therapy. |
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ISSN: | 0020-7136 1097-0215 |
DOI: | 10.1002/ijc.29832 |