Purpose: This study evaluates the cytotoxicity of AuNPs coated with polyallylamine (AuNPs-PAA) and conjugated or not to the epidermal growth factor receptor (EGFR)-targeting antibody Cetuximab (AuNPs-PAA-Ctxb) in normal human kidney (HK-2), liver (THLE-2) and microvascular endothelial (TIME) cells, and compares it with two cancer cell lines that are EGFR-overexpressing (A431) or EGFR-negative (MDA-MB-453). Results: Conjugation of Cetuximab to AuNPs-PAA increased the AuNPs-PAA-Ctxb interactions with cells, but reduced their cytotoxicity. TIME cells exhibited the strongest reduction in viability after exposure to AuNPs-PAA(±Ctxb), followed by THLE-2, MDA-MB-453, HK-2 and A431 cells. This cell type-dependent sensitivity was strongly correlated to the inhibition of thioredoxin reductase (TrxR) and glutathione reductase (GR), and to the depolarization of the mitochondrial membrane potential. Both are suggested to initiate apoptosis, which was indeed detected in a concentration- and time-dependent manner. The role of oxidative stress in AuNPs-PAA(±Ctxb)-induced cytotoxicity was demonstrated by co-incubation of the cells with N-acetyl L-cysteine (NAC), which significantly decreased apoptosis and mitochondrial membrane depolarization. Conclusion: This study helps to identify the cells and tissues that could be sensitive to AuNPs and deepens the understanding of the risks associated with the use of AuNPs in vivo.

BackgroundThe aim of this study was to elucidate the possible role of cerebral saturation monitoring in the post-cardiac arrest setting.MethodsCerebral tissue saturation (SctO2) was measured in 107 successfully resuscitated out-of-hospital cardiac arrest patients for 48 hours between 2011 and 2015. All patients were treated with targeted temperature management, 24 hours at 33 °C and rewarming at 0.3 °C per hour. A threshold analysis was performed as well as a linear mixed models analysis for continuous SctO2 data to compare the relation between SctO2 and favorable (cerebral performance category (CPC) 1–2) and unfavorable outcome (CPC 3–4–5) at 180 days post-cardiac arrest in OHCA patients.ResultsOf the 107 patients, 50 (47 %) had a favorable neurological outcome at 180 days post-cardiac arrest. Mean SctO2 over 48 hours was 68 % ± 4 in patients with a favorable outcome compared to 66 % ± 5 for patients with an unfavorable outcome (p = 0.035). No reliable SctO2 threshold was able to predict favorable neurological outcome. A significant different course of SctO2 was observed, represented by a logarithmic and linear course of SctO2 in patients with favorable outcome and unfavorable outcome, respectively (p < 0.001). During the rewarming phase, significant higher SctO2 values were observed in patients with a favorable neurological outcome (p = 0.046).ConclusionsThis study represents the largest post-resuscitation cohort evaluated using NIRS technology, including a sizeable cohort of balloon-assisted patients. Although a significant difference was observed in the overall course of SctO2 between OHCA patients with a favorable and unfavorable outcome, the margin was too small to likely represent functional outcome differentiation based on SctO2 alone. As such, these results given such methodology as performed in this study suggest that NIRS is insufficient by itself to serve in outcome prognostication, but there may remain benefit when incorporated into a multi-neuromonitoring bedside assessment algorithm.

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Samarium-153 is a promising theranostic radionuclide, but low molar activities (Am) resulting from its current production route render it unsuitable for targeted radionuclide therapy (TRNT). Recent efforts combining neutron activation of 152Sm in the SCK CEN BR2 reactor with mass separation at CERN/MEDICIS yielded high-Am 153Sm. In this proof-of-concept study, we further evaluated the potential of high-Am 153Sm for TRNT by radiolabeling to DOTA-TATE, a well-established carrier molecule binding the somatostatin receptor 2 (SSTR2) that is highly expressed in gastroenteropancreatic neuroendocrine tumors. DOTA-TATE was labeled with 153Sm and remained stable up to 7 days in relevant media. The binding specificity and high internalization rate were validated on SSTR2-expressing CA20948 cells. In vitro biological evaluation showed that [153Sm]Sm-DOTA-TATE was able to reduce CA20948 cell viability and clonogenic potential in an activity-dependent manner. Biodistribution studies in healthy and CA20948 xenografted mice revealed that [153Sm]Sm-DOTA-TATE was rapidly cleared and profound tumor uptake and retention was observed whilst these were limited in normal tissues. This proof-of-concept study showed the potential of mass-separated 153Sm for TRNT and could open doors towards wider applications of mass separation in medical isotope production.