Speciation and Bioavailability Measurements of Environmental Plutonium Using Diffusion in Thin Films.

The biological uptake of plutonium (Pu) in aquatic ecosystems is of particular concern since it is an alpha-particle emitter with long half-life which can potentially contribute to the exposure of biota and humans. The diffusive gradients in thin films technique is introduced here for in-situ measurements of Pu bioavailability and speciation. A diffusion cell constructed for laboratory experiments with Pu and the newly developed protocol make it possible to simulate the environmental behavior of Pu in model solutions of various chemical compositions. Adjustment of the oxidation states to Pu(IV) and Pu(V) described in this protocol is essential in order to investigate the complex redox chemistry of plutonium in the environment. The calibration of this technique and the results obtained in the laboratory experiments enable to develop a specific DGT device for in-situ Pu measurements in freshwaters. Accelerator-based mass-spectrometry measurements of Pu accumulated by DGTs in a karst spring allowed determining the bioavailability of Pu in a mineral freshwater environment. Application of this protocol for Pu measurements using DGT devices has a large potential to improve our understanding of the speciation and the biological transfer of Pu in aquatic ecosystems

Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study.

BACKGROUND: Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma. METHODS: Eligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing practice facility for 22-day lifileucel manufacturing. Patients received a non-myeloablative lymphodepletion regimen, a single lifileucel infusion, and up to six doses of high-dose interleukin-2. The primary endpoint was IRC-assessed ORR (Response Evaluation Criteria in Solid Tumors V.1.1). RESULTS: The Full Analysis Set consisted of 153 patients treated with lifileucel, including longer-term follow-up on the 66 patients previously reported. Patients had received a median of 3.0 lines of prior therapy (81.7% received both anti-programmed cell death protein 1 and anti-cytotoxic lymphocyte-associated protein 4) and had high disease burden at baseline (median target lesion sum of diameters (SOD): 97.8 mm; lactate dehydrogenase (LDH) >upper limit of normal: 54.2%). ORR was 31.4% (95% CI: 24.1% to 39.4%), with 8 complete responses and 40 partial responses. Median duration of response was not reached at a median study follow-up of 27.6 months, with 41.7% of the responses maintained for ≥18 months. Median overall survival and progression-free survival were 13.9 and 4.1 months, respectively. Multivariable analyses adjusted for Eastern Cooperative Oncology Group performance status demonstrated that elevated LDH and target lesion SOD >median were independently correlated with ORR (p=0.008); patients with normal LDH and SOD <median had greater likelihood of response than those with either (OR=2.08) or both (OR=4.42) risk factors. The most common grade 3/4 treatment-emergent adverse events (≥30%) were thrombocytopenia (76.9%), anemia (50.0%), and febrile neutropenia (41.7%). CONCLUSIONS: Investigational lifileucel demonstrated clinically meaningful activity in heavily pretreated patients with advanced melanoma and high tumor burden. Durable responses and a favorable safety profile support the potential benefit of one-time lifileucel TIL cell therapy in patients with limited treatment options in ICI-refractory disease

An investigation of aspects of radiochemical purity of ^99mTc-labelled human serum albumin nanocolloid.

Nanocolloidal human serum albumin radiolabelled with &lt;sup&gt;99m&lt;/sup&gt; Tc provides a diagnostic radiopharmaceutical for sentinel node lymphoscintigraphy. NanoHSA (Nanotop), a commercially available kit, enables the simple preparation of this radiopharmaceutical via reconstitution with pertechnetate eluted from a generator. Thin-layer chromatography is widely used for determining radiochemical purity in clinical nuclear medicine. Quality control methods recommended by the manufacturer were sometimes reported to yield variable results. Therefore, we proposed and evaluated three alternative thin-layer chromatography methods for the quality control of [ &lt;sup&gt;99m&lt;/sup&gt; Tc]Tc-NanoHSA from a commercially available kit. The radiochemical purity of [ &lt;sup&gt;99m&lt;/sup&gt; Tc]Tc-NanoHSA determined with all methods was reproducible and met the requirements of the SPC and the European Pharmacopoeia (≥ 95%). Our quality control using iTLC-SG chromatographic paper in methyl ethyl ketone mobile phase identified only free pertechnetate as impurity, resulting in &gt; 99% RCP. The quality control using iTLC-SG in 85% methanol or iTLC-SA in 0.9% NaCl identified an additional small fraction of a hydrophilic impurity, resulting in 95-97% RCP. Glucose was identified as a potential &lt;sup&gt;99m&lt;/sup&gt; Tc-carrying hydrophilic species contributing to hydrophilic impurities. Our quality control of [ &lt;sup&gt;99m&lt;/sup&gt; Tc]Tc-NanoHSA with non-polar mobile phase tended to underestimate the amount of hydrophilic impurities, although without compromising the final quality of the radiopharmaceutical. Alternative TLC methods using aqueous mobile phases enabled a more accurate determination of hydrophilic impurities

WC/a-C nanocomposite thin films: Optical and electrical properties

WC/amorphous carbon (a-C) thin films were deposited by dual magnetron sputtering from individual WC and graphite targets. The influence of film composition and microstructure on the optical and electrical properties was investigated. As evidenced by x-ray photoelectron spectroscopy and grazing angle x-ray diffraction measurements, the WC/a-C films are composite materials made of hexagonal W2C and/or cubic beta-WC1-X nanocrystallites embedded in (a-C) matrix. The optical properties were studied by spectroscopic ellipsometry and the electrical resistivity was measured by the van der Pauw method between 20 and 300 K. Both the optical and the electrical properties of the WC/a-C films are correlated with the chemical composition and microstructure evolution caused by a-C addition. The optical properties of W2C/a-C and beta-WC1-x/a-C films with a-C content <= 10 at. % are explained by modeling their dielectric functions by a set of Drude-Lorentz oscillators. Further increase in a-C content leads only to the formation of beta-WC1-x/a-C nanocomposite structures and their optical properties progressively evolve to those of a-C single phase. The electrical resistivity as a function of the temperature of all the films exhibits a negative temperature coefficient of resistivity. Theoretical fitting using the grain-boundary scattering model shows that the transport properties are mainly limited by the grain size and electron mean free path parameters

Radionuclides in the Environment in Switzerland: A Retrospective Study of Transfer from Soil to the Human Body.

Natural radionuclides are ubiquitous in the environment. In addition, artificial radionuclides are present in the Swiss environment after the fallout of the nuclear bomb tests of the 1950s and 1960s, after the accident of the Chernobyl nuclear power plant, or after authorized discharges from the Swiss nuclear power plants and research centres. These radionuclides can create a radiological hazard to the environment and humans because of the increased risk of cancer due to the ionizing radiation they produce. Here we show that some of these radionuclides have made their way from the air or the soil to the human body, where they target mostly the skeleton. However, the activity levels of 90 Sr, 239 Pu and 240 Pu, 226 Ra and 210 Pb/ 210 Po found in the human body remain very low and do not represent a public health issue at the current body burden

Advances in Cholangiocarcinoma Treatment in the Personalized Medicine Era

Cholangiocarcinoma is amongst the most common primary tumors of the liver, second only to hepatocellular carcinoma, and it accounts for approximately 15% of primary hepatic malignancies [1]. Cholangiocarcinoma is sub-classified as intrahepatic (ICCA), perihilar (PCCA) or distal (DCCA), according to its anatomical location [2]. Regardless of location, cholangiocarcinoma carries a poor prognosis, mainly due to paucity of effective therapy options and advanced disease at presentation. The American Cancer Society determined a 5-year relative survival rate of 8% for all patients with intrahepatic bile duct cancer and 10% for its extrahepatic counterpart. Even localized disease carries poor survival of 24% and 15% for ICCA and extrahepatic cholangiocarcinoma, respectively [3].&nbsp;</p