Fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) is a highly promising and emerging technique for biomedical applications because of its deeper tissue penetration capability and higher signal-background ratio (SBR) compared to traditional imaging approaches using the shorter emission wavelength windows. [1] Numerous novel NIR-II fluorophores have been developed and evaluated in small animal models. [1] Importantly, a conventional NIR Fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds great promise for deep tissue visualization. Development of novel clinical translatable NIR-II probes is crucial for realizing the medical applications of NIR-II fluorescence imaging. Herein, the glutathione-capped gold nanoclusters (AuNCs, specifically Au 25 (SG) 18) demonstrate highly efficient binding capability to hydroxyapatite in vitro for the first time. Further in vivo NIR-II fluorescence imaging of AuNCs indicate that they accumulate in bone tissues with high contrast and signal-background ratio. AuNCs are also mainly and quickly excreted from body through renal system, showing excellent ribs and thoracic vertebra imaging because of no background signal in liver and spleen. The deep tissue penetration capability and high resolution of AuNCs in NIR-II imaging render their great potential for fluorescence-guided surgery like spinal pedicle screw implantation. Overall, AuNCs are highly promising and clinical translatable NIR-II imaging probe for visualizing bone and bone related abnormalities.

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.

Statement of significance ICOS ImmunoPET is a promising strategy to noninvasively predict and monitor immunotherapy response. Research.

In vivo Imaging of Activated Chimeric Antigen Receptor T Cells. Conflict-of-interest disclosures SSG is the founder and equity holder of CellSight Inc. that develops and translates strategies for imaging cell trafficking/transplantation. CLM holds several patent applications in the area of CAR T cell immunotherapy, is a founder of, holds equity in, and receives consulting fees from Lyell Immunopharma, has received consulting fees from NeoImmune Tech, Nektar Therapeutics and Apricity Health and royalties from Juno Therapeutics for the CD22-CAR. All other authors have declared that no conflict of interest exists. Significance ICOS-immunoPET enables in vivo imaging of activated CAR T cells at the tumor site without the need for incorporation of reporter transgenes or ex vivo biolabeling. Research.