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Meeting ReportOncology: Basic & Translational

A PET imaging approach for monitoring the therapeutically induced dynamic changes of active mutant EGFR kinase-expression in Preclinical and Clinical non-small cell lung carcinomas

Xilin Sun, Zuoyu Xu, CHANGJIU ZHAO and Kai Wang
Journal of Nuclear Medicine May 2019, 60 (supplement 1) 660;
Xilin Sun
2TOF-PET/CT/MR center The Fourth Hospital of Harbin Medical University Harbin China
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Zuoyu Xu
2TOF-PET/CT/MR center The Fourth Hospital of Harbin Medical University Harbin China
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CHANGJIU ZHAO
14th Hospital of Harbin Medical University HARBIN China
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Kai Wang
2TOF-PET/CT/MR center The Fourth Hospital of Harbin Medical University Harbin China
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Abstract

660

Introduction: There's no doubt that determining epidermal growth factor receptor (EGFR) mutation status are of great significance for guiding target treatment in EGFR-mutant NSCLC patients. Clinical studies have shown chemotherapy had better efficacy in patients with mutant EGFR than wild type either, which means this treatment method may have potential molecular mechanism oninterferingEGFR signal pathway. Under this situation, accuratelymonitoring the dynamic changes ofactivemutant EGFR is crucial for NSCLC patients both receiving target treatmentand chemotherapy.18F-MPG is an 18F-labeled small molecular tyrosine kinase inhibitor (TKI)probe recently developed in our laboratory that has higher mutant EGFR targeting specificity to enhanced tumor uptake. In this study, we want to investigate whether the high specificity to active mutant EGFR PET tracer 18F-MPG can monitor early response of NSCLC tumors received target therapy and chemotherapy.

Methods: HCC827 tumor models were treated with PBS, Gefitinib or Carboplatin plus Pemetrexed (CP). 18F-MPG and 18F-FDG PET/CT imaging were performed at different time with Western Blot and immunofluorescence experiments to detectthe expression of EGFR signal pathway.EGFRmutantNSCLC patients without any treatment, received EGFR-TKIs treatment and CP underwent 18F-MPG and 18F-FDG PET/CT scans.

Results: The tumor uptake of 18F-MPG decreased significantly on day 2, 4 after Gefitinb treatment and day 21 after CP. The tumor uptake of 18F-FDG only decreased on day 2, 4 after Gefitinb treatment, but there was a little fluctuation after CP. Western Blot and immunofluorescence studies confirmed 18F-MPG uptake decrease correlated with changes in active mutant EGFR kinase-expression induced by two treatments. In patients with 18F-MPG PET/CT imaging, a mean SUVmaxdecrease were also observed after EGFR-TKIs treatment and Carboplatin plus Pemetrexed treatment. The mean SUVmaxwith 18F-FDG imaging in 3 group had not statistical significance.

Conclusions: 18F-MPG PET/CT imaging could accurately reflect the slight active mutant EGFR kinase-expression changes induced by EGFR-TKIsin a noninvasive way and real timeboth in preclinical and clinical. Cisplatin or Pemetrexed exposure resulted a dose-dependent decreasein active mutant EGFR NSCLCs, which this molecular level interfering on EGFR signal pathway can be also detected by 18F-MPGPET/CT imaging. Therefore,compared with 18F-FDG,18F-MPG PET/CT is a reliable tool in monitoring NSCLCs treatments, because of it is not easily affected by inflammation induced by chemotherapy and other factors. It has great potential in early treatment efficiency prediction, guiding follow-up treatment and evaluating prognosis in NSCLC therapy. References: [1] Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al.EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304(5676):1497-500 doi 10.1126/science.1099314. [2] Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al.Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. The New England journal of medicine 2009;361(10):947-57 doi 10.1056/NEJMoa0810699. [3] Sun X, Xiao Z, Chen G, Han Z, Liu Y, Zhang C, et al.A PET imaging approach for determining EGFR mutation status for improved lung cancer patient management. Science Translational Medicine 2018;10(431) doi 10.1126/scitranslmed.aan8840.

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Journal of Nuclear Medicine
Vol. 60, Issue supplement 1
May 1, 2019
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A PET imaging approach for monitoring the therapeutically induced dynamic changes of active mutant EGFR kinase-expression in Preclinical and Clinical non-small cell lung carcinomas
Xilin Sun, Zuoyu Xu, CHANGJIU ZHAO, Kai Wang
Journal of Nuclear Medicine May 2019, 60 (supplement 1) 660;

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A PET imaging approach for monitoring the therapeutically induced dynamic changes of active mutant EGFR kinase-expression in Preclinical and Clinical non-small cell lung carcinomas
Xilin Sun, Zuoyu Xu, CHANGJIU ZHAO, Kai Wang
Journal of Nuclear Medicine May 2019, 60 (supplement 1) 660;
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