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Non-small cell lung cancer (NSCLC) has one of the highest cancer-related mortality rates worldwide. In a subgroup of NSCLC, tumor growth is driven by epidermal growth factor receptors (EGFR) that harbor an activating mutation. These patients are best treated with EGFR tyrosine kinase inhibitors (EGFR TKI). Identifying the EGFR mutational status on a tumor biopsy or a liquid biopsy using tumor DNA sequencing techniques is the current approach to predict tumor response on EGFR TKI therapy. However, due to difficulty in reaching tumor sites, and varying inter- and intralesional tumor heterogeneity, biopsies are not always possible or representative of all tumor lesions, highlighting the need for alternative biomarkers that predict tumor response. Positron emission tomography (PET) studies using EGFR TKI-based tracers have shown that EGFR mutational status could be identified, and that tracer uptake could potentially be used as a biomarker for tumor response. However, despite their likely predictive and monitoring value, the EGFR TKI-PET biomarkers are not yet qualified to be used in the routine clinical practice. In this review, we will discuss the currently investigated EGFR-directed PET biomarkers, elaborate on the typical biomarker development process, and describe how the advances, challenges, and opportunities of EGFR PET biomarkers relate to this process on their way to qualification for routine clinical practice.

Third and second harmonic generation (THG/SHG) microscopy is a novel imaging technique that has been suggested as a promising clinical tool, mainly for cancer diagnosis. Here, we test for the first time a compact, transportable ex-vivo THG/SHG microscope (Tritos Diagnostics B.V.) for clinical use. In lung surgery, immediate feedback on the nature of the excised tissue is important. We will present the first results of an ongoing study in which we image both lung tumor tissue immediately after excision and frozen section biopsies, and compare the images to the golden standard histology. Prior to this study, we performed a set of experiments collecting 3D images of mouse lung tissue to show that the combination of THG and SHG microscopy reveals key lung morphology components.

Supplementary data. Table S1. Parent fractions (%). Table S2. Whole blood SUV. Table S3. Tumor [11C]erlotinib V T and K1 values. Table S4. Tumor [15O]H2O flow values. Table S5. SUV and TBR values (unitless). (DOC 170 kb)