Baseline metabolic tumor burdens at the level of whole-body tumor, primary tumor, nodal metastasis, and distant metastasis as measured with MTV and TLG on FDG PET are prognostic measures independent of clinical stage with low inter-observer variability and may be used to further stratify nonsurgical patients with NSCLC. This study also suggests MTV and TLG are better prognostic measures than SUV(max) and SUV(mean). These results will need to be validated in larger cohorts in a prospective study.
Nanoparticle-assisted drug delivery has been emerging as an active research area in recent years. The in vivo biodistribution of nanoparticle and its following mechanisms of biodegradation and/or excretion determine the feasibility and applicability of such a nano-delivery platform in the practical clinical translation. In this work we report the synthesis of the highly positive charge, near-infrared fluorescent mesoporous silica nanoparticles (MSNs) that demonstrate rapid hepatobiliary excretion, for use as traceable drug delivery platforms of high capacity. MSNs were incorporated with near-infrared fluorescent dye indocyanine green (ICG) via covalent or ionic bonding, to derive comparable constructs of significantly different net surface charge. In vivo fluorescence imaging and subsequent inductively coupled plasma-mass spectroscopy of harvested tissues, urine, and feces revealed markedly different uptake and elimination behaviors between the two conjugations; with more highly charged moieties (+34.4 mV at pH 7.4) being quickly excreted from the liver into the gastrointestinal tract, while less charged moieties (-17.6 mV at pH 7.4) remained sequestered within the liver. Taken together, these findings suggest that charge-dependent adsorption of serum proteins greatly facilitates the hepatobiliary excretion of silica nanoparticles, and that nanoparticle residence time in vivo can be regulated by manipulation of surface charge.
The characterization of near‐infrared (NIR) mesoporous silica nanoparticles (MSN) suitable for in vivo optical imaging with high efficiency is presented. Trimethylammonium groups modified MSN (MSN‐TA) with the average size of 50–100 nm was synthesized with incorporation of the TA groups into the framework of MSN. It was further adsorbed with indocyanine green (ICG) by electrostatic attraction to render MSN‐TA‐ICG as an efficient NIR contrast agent for in vivo optical imaging. The studies in stability of MSN‐TA‐ICG against pH indicated the bonding is stable over the range from acidic to physiological pH. The in vivo biodistribution of MSN‐TA‐ICG in anesthetized rat demonstrated a rather strong and stable fluorescence of MSN‐TA‐ICG that prominent in the organ of liver. Transmission electron microscopy (TEM) imaging and elemental analysis of silicon further manifested the physical and quantitative residences of MSN‐TA‐ICG in major organs. This is the first report of MSN functionalized with NIR‐ICG capable of optical imaging in vivo.
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