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

• Published in: International journal of cancer Vol. 138; no. 4; pp. 1003 - 1012
• Main Authors: Dai, Dong, Li, Xiao-Feng, Wang, Jian, Liu, Jian-Jing, Zhu, Yan-Jia, Zhang, Ying, Wang, Qi, Xu, Wen-Gui
• Format: Journal Article
• Language: English
• Published: United States 15.02.2016
• Subjects: Animals; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Blotting, Western; Carbon Radioisotopes - pharmacokinetics; Carbon Radioisotopes - pharmacology; Carcinoma, Non-Small-Cell Lung - diagnostic imaging; Carcinoma, Non-Small-Cell Lung - drug therapy; Drug Resistance, Neoplasm - physiology; Heterografts; Humans; Immunohistochemistry; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - drug therapy; Mice; Mice, Nude; Multimodal Imaging; Positron-Emission Tomography; Protein Kinase Inhibitors - pharmacokinetics; Protein Kinase Inhibitors - pharmacology; Quinazolines - pharmacokinetics; Quinazolines - pharmacology; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Tomography, X-Ray Computed; non-small cell lung cancer; positron emission tomography-computed tomography; epidermal growth factor receptor; epidermal growth factor receptor-tyrosine kinase inhibitor sensitivity
• ISSN: 1097-0215
• DOI: 10.1002/ijc.29832

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 xenografts. Four human NSCLC cell lines (HCC827, PC9, A549, and H1975) in the logarithmic phase were co-incubated with (11)C-PD153035 to analyze the correlation of (11)C-PD153035 uptake with EGFR-TKI sensitivity, and EGFR/pEGFR expression. Nude mice xenograft models bearing the four NSCLCs were prepared. (11)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 (11)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, (11)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 (11)C-PD153035 and individualized NSCLC therapy.