Professional Education


  • Doctor of Medicine, Unlisted School (2007)
  • Doctor of Science, Unlisted School (2017)

All Publications


  • Development of a SPECT Tracer to Image c-Met Expression in a Xenograft Model of Non-Small Cell Lung Cancer JOURNAL OF NUCLEAR MEDICINE Han, Z., Xiao, Y., Wang, K., Yan, J., Xiao, Z., Fang, F., Jin, Z., Liu, Y., Sun, X., Shen, B. 2018; 59 (11): 1686–91

    Abstract

    Elevated expression of the c-Met receptor plays a crucial role in cancers. In non-small cell lung cancer (NSCLC), aberrant activation of the c-Met signaling pathway contributes to tumorigenesis and cancer progression and may mediate acquired resistance to epidermal growth factor receptor-targeted therapy. c-Met is therefore emerging as a promising therapeutic target for NSCLC, and methods for noninvasive in vivo assessment of c-Met expression would improve NSCLC treatment and diagnosis. Methods: We developed a new c-Met-binding peptide (cMBP) radiotracer, 99mTc-hydrazine nicotinamide (HYNIC)-cMBP, for SPECT imaging. Cell uptake assays were performed on 2 NSCLC cell lines with different c-Met expressions: H1993 (high expression) and H1299 (no expression). In vivo tumor specificity was assessed by SPECT imaging in tumor-bearing mice at 0.5, 1, 2, and 4 h after injection of the probe. Blocking assays, biodistribution, and autoradiography were also conducted to determine probe specificity. Results:99mTc-HYNIC-cMBP was prepared with high efficiency and showed higher uptake in H1993 cells than in H1299 cells. Biodistribution and autoradiography also showed significantly higher percentages of the injected dose for 99mTc-HYNIC-cMBP in H1993 tumors than in H1299 tumors at 0.5 h (4.74 ± 1.43%/g and 1.00 ± 0.37%/g, respectively; P < 0.05). H1993 tumors were clearly visualized at 0.5 h in SPECT images, whereas H1299 tumors were not observed at any time. The specificity of 99mTc-HYNIC-cMBP for c-Met was demonstrated by a competitive block with an excess of nonradiolabeled peptide. Conclusion: For c-Met-targeted SPECT imaging of NSCLC, we developed 99mTc-HYNIC-cMBP, a tracer that specifically binds to c-Met with favorable pharmacokinetics in vitro and in vivo.

    View details for PubMedID 29777004

  • A PET imaging approach for determining EGFR mutation status for improved lung cancer patient management SCIENCE TRANSLATIONAL MEDICINE Sun, X., Xiao, Z., Chen, G., Han, Z., Liu, Y., Zhang, C., Sun, Y., Song, Y., Wang, K., Fang, F., Wang, X., Lin, Y., Xu, L., Shao, L., Li, J., Cheng, Z., Gambhir, S., Shen, B. 2018; 10 (431)

    Abstract

    Tumor heterogeneity and changes in epidermal growth factor receptor (EGFR) mutation status over time challenge the design of effective EGFR tyrosine kinase inhibitor (TKI) treatment strategies for non-small cell lung cancer (NSCLC). Therefore, there is an urgent need to develop techniques for comprehensive tumor EGFR profiling in real time, particularly in lung cancer precision medicine trials. We report a positron emission tomography (PET) tracer, N-(3-chloro-4-fluorophenyl)-7-(2-(2-(2-(2-18F-fluoroethoxy) ethoxy) ethoxy) ethoxy)-6-methoxyquinazolin-4-amine (18F-MPG), with high specificity to activating EGFR mutant kinase. We evaluate the feasibility of using 18F-MPG PET for noninvasive imaging and quantification of EGFR-activating mutation status in preclinical models of NSCLC and in patients with primary and metastatic NSCLC tumors. 18F-MPG PET in NSCLC animal models showed a significant correlation (R2 = 0.9050) between 18F-MPG uptake and activating EGFR mutation status. In clinical studies with NSCLC patients (n = 75), the concordance between the detection of EGFR activation by 18F-MPG PET/computed tomography (CT) and tissue biopsy reached 84.29%. There was a greater response to EGFR-TKIs (81.58% versus 6.06%) and longer median progression-free survival (348 days versus 183 days) in NSCLC patients when 18F-MPG PET/CT SUVmax (maximum standard uptake value) was ≥2.23 versus <2.23. Our study demonstrates that 18F-MPG PET/CT is a powerful method for precise quantification of EGFR-activating mutation status in NSCLC patients, and it is a promising strategy for noninvasively identifying patients sensitive to EGFR-TKIs and for monitoring the efficacy of EGFR-TKI therapy.

    View details for PubMedID 29515002

  • Evaluation of Tc-99m-HYNIC-MPG as a novel SPECT radiotracer to detect EGFR-activating mutations in NSCLC ONCOTARGET Xiao, Z., Song, Y., Kai, W., Sun, X., Shen, B. 2017; 8 (25): 40732–40

    Abstract

    Tyrosine kinase inhibitors (EGFR-TKIs) targeting the epidermal growth factor receptor (EGFR) have been used in non-small cell lung carcinoma (NSCLC) for years with promising results, in particular in patients with activating mutations in the EGFR kinase domain (exon 19 E746-A750 deletion or exon 21 L858R point mutation). However, despite their great success in the clinic, a significant number of patients do not respond to EGFR-TKIs, such as those carrying the L858R/T790M mutation or EGFR wild type. Thus, detecting the EGFR mutation status before EGFR-TKIs therapy is essential to ensure its efficacy. In this study, we report a novel SPECT tracer 99mTc-HYNIC-MPG that binds specifically to activating mutant EGFR and which could therefore be used to noninvasively select patients sensitive to EGFR-TKIs. We evaluated the capacity of 99mTc-HYNIC-MPG in detecting EGFR-activating mutations both in vitro and in vivo using four human NSCLC cell lines (PC9, H1975, H358 and H520). 99mTc-HYNIC-MPG had significantly higher accumulation in PC9 tumor cells when compared to H1975, H358 and H520 tumors cells, which may be due to the activating mutations (exon 19 deletion) in EGFR tyrosine kinase domain in PC9 cells. Thus, 99mTc-HYNIC-MPG SPECT imaging may be used to identify NSCLC tumors with a potential high response rate to EGFR-TKIs.

    View details for DOI 10.18632/oncotarget.17251

    View details for Web of Science ID 000404283700065

    View details for PubMedID 28489575

    View details for PubMedCentralID PMC5522229

  • Development and Evaluation of F-18-IRS for Molecular Imaging Mutant EGF Receptors in NSCLC SCIENTIFIC REPORTS Song, Y., Xiao, Z., Wang, K., Wang, X., Zhang, C., Fang, F., Sun, X., Shen, B. 2017; 7: 3121

    Abstract

    To prepare and evaluate a new radiotracer 18F-IRS for molecular imaging mutant EGF Receptors in vitro and vivo. Uptake and efflux of 18F-IRS were performed with four NSCLC cell lines including HCC827, H1975, H358 and H520. In vivo tumor targeting and pharmacokinetics of the radiotracers were also evaluated in HCC827, H1975, H358 and H520 tumor-bearing nude mice by PET/CT imaging. Ex vivo biodistribution assays were performed to quantify the accumulation of 18F-IRS in vivo. We also performed 18F-IRS PET/CT imaging of three patients with NSCLC. We labeled this small molecule with QD620 for flow cytometry and confocal imaging analyses. The uptakes of 18F-IRS by HCC827 and HCC827 tumors were significantly higher than those of H358, H1975 and H520, and they were reduced by the addition of 100 μM of gefitinib. Biodistribution experiments showed an accumulation of 18F-IRS in tumors of HCC827 xenografts. Flow cytometry and confocal imaging with QD620-IRS further demonstrated that binding specifically to HCC827 cells. 18F-IRS accumulation was preferential in the tumor, which was NSCLC with responsive EGFR exon 19 deleted. 18F-IRS showed high binding stability and specificity to 19 exon deleted EGFR mutation in vitro and vivo.

    View details for PubMedID 28600491

  • One-step radiosynthesis of F-18-IRS: A novel radiotracer targeting mutant EGFR in NSCLC for PET/CT imaging BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Xiao, Z., Song, Y., Wang, K., Sun, X., Shen, B. 2016; 26 (24): 5985–88

    Abstract

    EGFR (epidermal growth factor receptor) targeted therapy has shown great success in clinical comparing with chemotherapy in EGFR mutation NSCLCs. Such as, gefitinib, first generation EGFR TKI, has obviously prolonged the FPS (progression free survival) of the subgroup of patients, but to those who did not get a certain mutation in EGFR kinase domain, the outcome is poor. In view of this situation, scientists have synthesized many radiotracers for selecting the right people by PET/CT imaging to NSCLC TKI therapy. In this study, we developed a novel PET radiotracer 18F-IRS in one-step with a radio yield 20% (non-corrected), radiochemistry>98.5%, specific activity>105GBq/μmol, the pharmacokinetics and capacity of the tracer binding to mutant EGFR were evaluated both in vitro and in vivo.

    View details for DOI 10.1016/j.bmcl.2016.10.084

    View details for Web of Science ID 000389784500030

    View details for PubMedID 27825546