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, -(3-chloro-4-fluorophenyl)-7-(2-(2-(2-(2-F-fluoroethoxy) ethoxy) ethoxy) ethoxy)-6-methoxyquinazolin-4-amine (F-MPG), with high specificity to activating EGFR mutant kinase. We evaluate the feasibility of using F-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.F-MPG PET in NSCLC animal models showed a significant correlation ( = 0.9050) between F-MPG uptake and activating EGFR mutation status. In clinical studies with NSCLC patients ( = 75), the concordance between the detection of EGFR activation by F-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 whenF-MPG PET/CT SUV (maximum standard uptake value) was ≥2.23 versus <2.23. Our study demonstrates that F-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.

Targeting the medical monitoring applications of wireless body area networks (WBANs), a hybrid medium access control protocol using an interrupt mechanism (I-MAC) is proposed to improve the energy and time slot utilization efficiency and to meet the data delivery delay requirement at the same time. Unlike existing hybrid MAC protocols, a superframe structure with a longer length is adopted to avoid unnecessary beacons. The time slots are mostly allocated to nodes with periodic data sources. Short interruption slots are inserted into the superframe to convey the urgent data and to guarantee the real-time requirements of these data. During these interruption slots, the coordinator can break the running superframe and start a new superframe. A contention access period (CAP) is only activated when there are more data that need to be delivered. Experimental results show the effectiveness of the proposed MAC protocol in WBANs with low urgent traffic.

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.