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Purpose: We investigated the characteristics of radiation-induced current in nano-porous pellet and thin-film anodized tantalum exposed to kVp X-ray beams. We aim at developing a large area (≫cm2) thin-film radiation sensor for medical, national security and space applications. Methods: Large area (few cm2) micro-thin Ta foils were anodized and coated with a counter electrode made of conductive polymer. In addition, several types of commercial electrolytic porous tantalum capacitors were assembled and prepared for irradiation with kVp X-rays. We measured dark current (leakage) as well as transient radiation-induced currents as a function of external voltage bias. Results: Large transient currents (up to 50 nA) under X-ray irradiation (dose rate of about 3 cGy/s) were measured in Ta2O5 capacitors. Small nano-porous Ta and large-area flat Ta foil capacitors show similar current–voltage characteristic curve after accounting for different X-ray attenuation in capacitor geometry. The signal is larger for thicker capacitor oxide. A non-negligible signal for null external voltage bias is observed, which is explained by fast electron production in Ta foils. Conclusions: Anodized tantalum is a promising material for use in large-area, self-powered radiation sensors for X-ray detection and for energy harvesting. [ABSTRACT FROM AUTHOR]

Simple Summary: Current treatment options for advanced cervical cancer are limited, with a 5-year overall survival rate of 17%. New effective therapeutic approaches that can increase survival and reduce disparities are greatly needed. In this study, an approach using a multifunctional liquid immunogenic fiducial eluter (LIFE) that can provide image contrast and enhance therapeutic efficacy during hypo-fractionated radiotherapy is investigated. We found this technique provides both computed tomography (CT) and magnetic resonance imaging (MRI) image contrast to guide radiotherapy. Additionally, in a model of metastatic cervical cancer, local treatment with LIFE and radiotherapy resulted in distant disease control and improvement in survival. Successful development of this approach may provide a short therapeutic option that could enhance treatment outcomes and reduce disparities. LIFE Biomaterial may also significantly provide a cheaper and convenient alternative to prolonged systemic treatment with opportunities to increase access to care and reduce health outcome disparities. Globally, cervical cancer is the fourth leading cancer among women and is dominant in resource-poor settings in its occurrence and mortality. This study focuses on developing liquid immunogenic fiducial eluter (LIFE) Biomaterial with components that include biodegradable polymers, nanoparticles, and an immunoadjuvant. LIFE Biomaterial is designed to provide image guidance during radiotherapy similar to clinically used liquid fiducials while enhancing therapeutic efficacy for advanced cervical cancer. C57BL6 mice were used to grow subcutaneous tumors on bilateral flanks. The tumor on one flank was then treated using LIFE Biomaterial prepared with the immunoadjuvant anti-CD40, with/without radiotherapy at 6 Gy. Computed tomography (CT) and magnetic resonance (MR) imaging visibility were also evaluated in human cadavers. A pharmacodynamics study was also conducted to assess the safety of LIFE Biomaterial in healthy C57BL6 female mice. Results showed that LIFE Biomaterial could provide both CT and MR imaging contrast over time. Inhibition in tumor growth and prolonged significant survival (* p < 0.05) were consistently observed for groups treated with the combination of radiotherapy and LIFE Biomaterial, highlighting the potential for this strategy. Minimal toxicity was observed for healthy mice treated with LIFE Biomaterial with/without anti-CD40 in comparison to non-treated cohorts. The results demonstrate promise for the further development and clinical translation of this approach to enhance the survival and quality of life of patients with advanced cervical cancer. [ABSTRACT FROM AUTHOR]

The use of an immunogenic smart radiotherapy biomaterial (iSRB) for the delivery of anti-CD40 is effective in treating different cancers in animal models. This study further characterizes the use of iSRBs to evaluate any associated toxicity in healthy C57BL6 mice. iSRBs were fabricated using a poly-lactic-co-glycolic-acid (PLGA) polymer mixed with titanium dioxide (TiO2) nanoparticles incorporated into its matrix. Animal studies included investigations of freely injected anti-CD40, anti-CD40-loaded iSRBs, unloaded iSRBs and control (healthy) animal cohorts. Mice were euthanized at pre-determined time points post-treatment to evaluate the serum chemistry pertaining to kidney and liver toxicity and cell blood count parameters, as well as pathology reports on organs of interest. Results showed comparable liver and kidney function in all cohorts. The results indicate that using iSRBs with or without anti-CD40 does not result in any significant toxicity compared to healthy untreated animals. The findings provide a useful reference for further studies aimed at optimizing the therapeutic efficacy and safety of iSRBs and further clinical translation work. [ABSTRACT FROM AUTHOR]

Recent studies have highlighted the potential of smart radiotherapy biomaterials (SRBs) for combining radiotherapy and immunotherapy. These SRBs include smart fiducial markers and smart nanoparticles made with high atomic number materials that can provide requisite image contrast during radiotherapy, increase tumor immunogenicity, and provide sustained local delivery of immunotherapy. Here, we review the state-of-the-art in this area of research, the challenges and opportunities, with a focus on in situ vaccination to expand the role of radiotherapy in the treatment of both local and metastatic disease. A roadmap for clinical translation is outlined with a focus on specific cancers where such an approach is readily translatable or will have the highest impact. The potential of FLASH radiotherapy to synergize with SRBs is discussed including prospects for using SRBs in place of currently used inert radiotherapy biomaterials such as fiducial markers, or spacers. While the bulk of this review focuses on the last decade, in some cases, relevant foundational work extends as far back as the last two and half decades. [ABSTRACT FROM AUTHOR]