Size-Dependent Blue Emission from Europium-Doped Strontium Fluoride Nanoscintillators for X-Ray-Activated Photodynamic Therapy.

Successful implementation of X-ray-activated photodynamic therapy (X-PDT) is challenging because most photosensitizers (PSs) absorb light in the blue region, but few nanoscintillators produce efficient blue scintillation. Here, efficient blue-emitting SrF2:Eu scintillating nanoparticles (ScNPs) are developed. The optimized synthesis conditions result in cubic nanoparticles with ≈32 nm diameter and blue emission at 416 nm. Coating them with the meso-tetra(n-methyl-4-pyridyl) porphyrin (TMPyP) in a core-shell structure (SrF@TMPyP) results in maximum singlet oxygen (1O2) generation upon X-ray irradiation for nanoparticles with 6TMPyP depositions (SrF@6TMPyP). The 1O2 generation is directly proportional to the dose, does not vary in the low-energy X-ray range (48-160 kVp), but is 21% higher when irradiated with low-energy X-rays than irradiations with higher energy gamma rays. In the clonogenic assay, cancer cells treated with SrF@6TMPyP and exposed to X-rays present a significantly reduced survival fraction compared to the controls. The SrF2:Eu ScNPs and their conjugates stand out as tunable nanoplatforms for X-PDT due to the efficient blue emission from the SrF2:Eu cores; the ability to adjust the scintillation emission in terms of color and intensity by controlling the nanoparticle size; the efficient 1O2 production when conjugated to a PS and the efficacy of killing cancer cells.

Tuning ultrasmall theranostic nanoparticles for MRI contrast and radiation dose amplification.

Background: The introduction of magnetic resonance (MR)-guided radiation treatment planning has opened a new space for theranostic nanoparticles to reduce acute toxicity while improving local control. In this work, second-generation AGuIX® nanoparticles (AGuIX-Bi) are synthesized and validated. AGuIX-Bi are shown to maintain MR positive contrast while further amplifying the radiation dose by the replacement of some Gd3+ cations with higher Z Bi3+. These next-generation nanoparticles are based on the AGuIX® platform, which is currently being evaluated in multiple Phase II clinical trials in combination with radiotherapy. Methods: In this clinically scalable methodology, AGuIX® is used as an initial chelation platform to exchange Gd3+ for Bi3+. AGuIX-Bi nanoparticles are synthesized with three ratios of Gd/Bi, each maintaining MR contrast while further amplifying radiation dose relative to Bi3+. Safety, efficacy, and theranostic potential of the nanoparticles were evaluated in vitro and in vivo in a human non-small cell lung cancer model. Results: We demonstrated that increasing Bi3+ in the nanoparticles is associated with more DNA damage and improves in vivo efficacy with a statistically significant delay in tumor growth and 33% complete regression for the largest Bi/Gd ratio tested. The addition of Bi3+ by our synthetic method leads to nanoparticles that present slightly altered pharmacokinetics and lengthening of the period of high tumor accumulation with no observed evidence of toxicity. Conclusions: We confirmed the safety and enhanced efficacy of AGuIX-Bi with radiation therapy at the selected ratio of 30Gd/70Bi. These results provide crucial evidence towards patient translation.

Calculating the proportion of avoidable attendances at UK emergency departments: analysis of the Royal College of Emergency Medicine's Sentinel Site Survey data.

INTRODUCTION: Avoidable attendances (AAs; defined as non-urgent, self-referred patients who could be managed more effectively and efficiently by other services) have been identified as a contributor to ED crowding. Internationally, AAs have been estimated to constitute 10%-90% of ED attendances, with the UK 2013 Urgent and Emergency Care Review suggesting a figure of 40%. METHODS: This pilot study used data from the Royal College of Emergency Medicine's Sentinel Site Survey to estimate the proportion of AAs in 12 EDs across England on a standard day (20 March 2014). AAs were defined by an expert panel using questions from the survey. All patients attending the EDs were recorded with details of investigations and treatments received, and the proportion of patients meeting criteria for AA was calculated. RESULTS: Visits for 3044 patients were included. Based on these criteria, a mean of 19.4% (95% CI 18.0% to 20.8%) of attendances could be deemed avoidable. The lowest proportion of AAs reported was 10.7%, while the highest was 44.3%. Younger age was a significant predictor of AA with mean age of 38.6 years for all patients attending compared with 24.6 years for patients attending avoidably (p≤0.001). DISCUSSION: The proportion of AAs in this study was lower than many estimates in the literature, including that reported by the 2013 Urgent and Emergency Care Review. This suggests the ED is the most appropriate healthcare setting for many patients due to comprehensive investigations, treatments and capability for urgent referrals.The proportion of AAs is dependent on the defining criteria used, highlighting the need for a standardised, universal definition of an appropriate/avoidable ED attendance. This is essential to understanding how AAs contribute to the overall issue of crowding.