Rock Thermal Conductivity as Key Parameter for Geothermal Numerical Models

Abstract The geothermal energy applications are undergoing a rapid development. However, there are still several challenges in the successful exploitation of geothermal energy resources. A special effort is required to characterize the thermal properties of the ground and to implement the thermal energy transfer technologies. Aim of this study is to provide original heat conductivity values for rocks and sediments in regions included in the VIGOR Project (southern Italy), to overcome the existing lack of data. Thermal properties tests were performed on several samples, both in dry and wet conditions, using thermal analyzer operating following the Modified Transient Plane Source method

How Can We Help You?: An Instagram-Based Online Self-Help for Eating Disorders

In recent years, there has been a noticeable increase in online self-help treatments and peer-support programs for eating disorders. The possibility of easily accessing them anytime makes these programs an important support tool and an influencing source for increasing motivation to change. The aim of this work is to describe the #How can we help you? project, its initial feedback received from users, and its future directions. Researchers and clinicians developed an Instagram profile (Dicci Come Aiutarti) based on psychoeducation, aimed at orienting those suffering from a self-reported eating disorder towards clinical care, providing information about eating concerns and related constructs, and increasing motivation for treatment and illness awareness. The contents shared are based on narratives about people who had recovered from an eating disorder, importance and ability to change, and nutrition management. We have provided an overview of the needs of the Instagram profile users, a description of the main interactions recorded since the profile was opened, and examples of the unmet needs shared by users in direct messages. Future directions of the project concern the definition and formalization of the type of support provided by developing a psychoeducational and integrated program and also, the formulation of a research protocol able to assess the usability, effectiveness, and satisfaction of the Instagram profile. © 2023 by the authors

A radioiodinated rucaparib analogue as an Auger electron emitter for cancer therapy

Introduction: Radioligand therapy (RLT) is an expanding field that has shown great potential in the fight against cancer. Radionuclides that can be carried by selective ligands such as antibodies, peptides, and small molecules targeting cancerous cells have demonstrated a clear improvement in the move towards precision medicine. Poly (ADP-ribose) polymerase (PARP) is a family of enzymes involved in DNA damage repair signalling pathway, with PARP inhibitors olaparib, talazoparib, niraparib, veliparib, and rucaparib having FDA approval for cancer therapy in routine clinical use. Based on our previous work with the radiolabelled PARP inhibitor [18F]rucaparib, we replaced the fluorine-18 moiety, used for PET imaging, with iodine-123, a radionuclide used for SPECT imaging and Auger electron therapy, resulting in 8-[123I]iodo-5-(4-((methylamino)methyl)phenyl)-2,3,4,6-tetrahydro-1H-azepino[5,4,3-cd]indol-1-one, ([123I]GD1), as a potential radiopharmaceutical for RLT.Methods: [123I]GD1 was synthesized via copper-mediated radioiodination from a selected boronic esters precursor. In vitro uptake, retention, blocking, and effects on clonogenic survival with [123I]GD1 treatment were tested in a panel of cancer cell lines. Enzymatic inhibition of PARP by GD1 was also tested in a cell-free system. The biodistribution of [123I]GD1 was investigated by SPECT/CT in mice following intravenous administration.Results: Cell-free enzymatic inhibition and in vitro blocking experiments confirmed a modest ability of GD1 to inhibit PARP-1, IC50 = 239 nM. In vitro uptake of [123I]GD1 in different cell lines was dose dependent, and radiolabelled compound was retained in cells for &gt;2 h. Significantly reduced clonogenic survival was observed in vitro after exposure of cells for 1 h with as low as 50 kBq of [123I]GD1. The biodistribution of [123I]GD1 was further characterized in vivo showing both renal and hepatobiliary clearance pathways with a biphasic blood clearance.Conclusion: We present the development of a new theragnostic agent based on the rucaparib scaffold and its evaluation in in vitro and in vivo models. The data reported show that [123I]GD1 may have potential to be used as a theragnostic agent.</p

Imaging PARP with [18F]rucaparib in pancreatic cancer models

PURPOSE: Rucaparib, an FDA-approved PARP inhibitor, is used as a single agent in maintenance therapy to provide promising treatment efficacy with an acceptable safety profile in various types of BRCA-mutated cancers. However, not all patients receive the same benefit from rucaparib-maintenance therapy. A predictive biomarker to help with patient selection for rucaparib treatment and predict clinical benefit is therefore warranted. With this aim, we developed [18F]rucaparib, an 18F-labelled isotopologue of rucaparib, and employed it as a PARP-targeting agent for cancer imaging with PET. Here, we report the in vitro and in vivo evaluation of [18F]rucaparib in human pancreatic cancer models. METHOD: We incorporated the positron-emitting 18F isotope into rucaparib, enabling its use as a PET imaging agent. [18F]rucaparib binds to the DNA damage repair enzyme, PARP, allowing direct visualisation and measurement of PARP in cancerous models before and after PARP inhibition or other genotoxic cancer therapies, providing critical information for cancer diagnosis and therapy. Proof-of-concept evaluations were determined in pancreatic cancer models. RESULTS: Uptake of [18F]rucaparib was found to be mainly dependent on PARP1 expression. Induction of DNA damage increased PARP expression, thereby increasing uptake of [18F]rucaparib. In vivo studies revealed relatively fast blood clearance of [18F]rucaparib in PSN1 tumour-bearing mice, with a tumour uptake of 5.5 ± 0.5%ID/g (1 h after i.v. administration). In vitro and in vivo studies showed significant reduction of [18F]rucaparib uptake by addition of different PARP inhibitors, indicating PARP-selective binding. CONCLUSION: Taken together, we demonstrate the potential of [18F]rucaparib as a non-invasive PARP-targeting imaging agent for pancreatic cancers

[123I]CC1:A PARP-Targeting, Auger Electron-Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer

Poly(adenosine diphosphate ribose) polymerase (PARP) has emerged as an effective therapeutic strategy against cancer that targets the DNA damage repair enzyme. PARP-targeting compounds radiolabeled with an Auger electron-emitting radionuclide can be trapped close to damaged DNA in tumor tissue, where high ionizing potential and short range lead Auger electrons to kill cancer cells through the creation of complex DNA damage, with minimal damage to surrounding normal tissue. Here, we report on [ 123I]CC1, an 123I-labeled PARP inhibitor for radioligand therapy of cancer.Methods: Copper-mediated 123I iododeboronation of a boronic pinacol ester precursor afforded [ 123I]CC1. The level and specificity of cell uptake and the therapeutic efficacy of [ 123I]CC1 were determined in human breast carcinoma, pancreatic adenocarcinoma, and glioblastoma cells. Tumor uptake and tumor growth inhibition of [ 123I]CC1 were assessed in mice bearing human cancer xenografts (MDA-MB-231, PSN1, and U87MG).Results: In vitro and in vivo studies showed selective uptake of [ 123I]CC1 in all models. Significantly reduced clonogenicity, a proxy for tumor growth inhibition by ionizing radiation in vivo, was observed in vitro after treatment with as little as 10 Bq [ 123I]CC1. Biodistribution at 1 h after intravenous administration showed PSN1 tumor xenograft uptake of 0.9 ± 0.06 percentage injected dose per gram of tissue. Intravenous administration of a relatively low amount of [ 123I]CC1 (3 MBq) was able to significantly inhibit PSN1 xenograft tumor growth but was less effective in xenografts that expressed less PARP. [ 123I]CC1 did not cause significant toxicity to normal tissues.Conclusion: Taken together, these results show the potential of [ 123I]CC1 as a radioligand therapy for PARP-expressing cancers. </p

Radiofluorination of a highly potent ATM inhibitor as a potential PET imaging agent

PURPOSE: Ataxia telangiectasia mutated (ATM) is a key mediator of the DNA damage response, and several ATM inhibitors (ATMi) are currently undergoing early phase clinical trials for the treatment of cancer. A radiolabelled ATMi to determine drug pharmacokinetics could assist patient selection in a move towards more personalised medicine. The aim of this study was to synthesise and investigate the first 18F-labelled ATM inhibitor [18F]1 for non-invasive imaging of ATM protein and ATMi pharmacokinetics. METHODS: Radiofluorination of a confirmed selective ATM inhibitor (1) was achieved through substitution of a nitro-precursor with [18F]fluoride. Uptake of [18F]1 was assessed in vitro in H1299 lung cancer cells stably transfected with shRNA to reduce expression of ATM. Blocking studies using several non-radioactive ATM inhibitors assessed binding specificity to ATM. In vivo biodistribution studies were performed in wild-type and ATM-knockout C57BL/6 mice using PET/CT and ex vivo analysis. Uptake of [18F]1 in H1299 tumour xenografts was assessed in BALB/c nu/nu mice. RESULTS: Nitro-precursor 2 was synthesised with an overall yield of 12%. Radiofluorination of 2 achieved radiochemically pure [18F]1 in 80 ± 13 min with a radiochemical yield of 20 ± 13% (decay-corrected) and molar activities up to 79.5 GBq/μmol (n = 11). In vitro, cell-associated activity of [18F]1 increased over 1 h, and retention of [18F]1 dropped to 50% over 2 h. [18F]1 uptake did not correlate with ATM expression, but could be reduced significantly with an excess of known ATM inhibitors, demonstrating specific binding of [18F]1 to ATM. In vivo, fast hepatobiliary clearance was observed with tumour uptake ranging 0.13-0.90%ID/g after 1 h. CONCLUSION: Here, we report the first radiofluorination of an ATM inhibitor and its in vitro and in vivo biological evaluations, revealing the benefits but also some limitations of 18F-labelled ATM inhibitors

[123I]CC1:A PARP-Targeting, Auger Electron-Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer

Poly(adenosine diphosphate ribose) polymerase (PARP) has emerged as an effective therapeutic strategy against cancer that targets the DNA damage repair enzyme. PARP-targeting compounds radiolabeled with an Auger electron-emitting radionuclide can be trapped close to damaged DNA in tumor tissue, where high ionizing potential and short range lead Auger electrons to kill cancer cells through the creation of complex DNA damage, with minimal damage to surrounding normal tissue. Here, we report on [ 123I]CC1, an 123I-labeled PARP inhibitor for radioligand therapy of cancer.Methods: Copper-mediated 123I iododeboronation of a boronic pinacol ester precursor afforded [ 123I]CC1. The level and specificity of cell uptake and the therapeutic efficacy of [ 123I]CC1 were determined in human breast carcinoma, pancreatic adenocarcinoma, and glioblastoma cells. Tumor uptake and tumor growth inhibition of [ 123I]CC1 were assessed in mice bearing human cancer xenografts (MDA-MB-231, PSN1, and U87MG).Results: In vitro and in vivo studies showed selective uptake of [ 123I]CC1 in all models. Significantly reduced clonogenicity, a proxy for tumor growth inhibition by ionizing radiation in vivo, was observed in vitro after treatment with as little as 10 Bq [ 123I]CC1. Biodistribution at 1 h after intravenous administration showed PSN1 tumor xenograft uptake of 0.9 ± 0.06 percentage injected dose per gram of tissue. Intravenous administration of a relatively low amount of [ 123I]CC1 (3 MBq) was able to significantly inhibit PSN1 xenograft tumor growth but was less effective in xenografts that expressed less PARP. [ 123I]CC1 did not cause significant toxicity to normal tissues.Conclusion: Taken together, these results show the potential of [ 123I]CC1 as a radioligand therapy for PARP-expressing cancers. </p

multi‐patient dose synthesis of [18F]Flumazenil via a copper‐mediated 18F‐fluorination

Background Flumazenil (FMZ) is a functionally silent imidazobenzodiazepine which binds to the benzodiazepine binding site of approximately 75% of the brain γ-aminobutyric acid-A receptors (GABAARs). Positron Emission Tomography (PET) imaging of the GABAARs with [11C]FMZ has been used to evidence alterations in neuronal density, to assess target engagement of novel pharmacological agents, and to study disorders such as epilepsy and Huntington’s disease. Despite the potential of FMZ PET imaging the short half-life (t1/2) of carbon-11 (20 min) has limited the more widespread clinical use of [11C]FMZ. The fluorine-18 (18F) isotopologue with a longer t1/2 (110 min) is ideally suited to address this drawback. However, the majority of current radiochemical methods for the synthesis of [18F]FMZ are non-trivial and low yielding. We report a robust, automated protocol that is good manufacturing practice (GMP) compatible, and yields multi-patient doses of [18F]FMZ. Results The fully automated synthesis was developed on the Trasis AllinOne (AIO) platform using a single-use cassette. [18F]FMZ was synthesized in a one-step procedure from [18F]fluoride, via a copper-mediated 18F-fluorination of a boronate ester precursor. Purification was performed by semi-preparative radio-HPLC and the collected fraction formulated directly into the final product vial. The overall process from start of synthesis to delivery of product is approximately 55 min. Starting with an initial activity of 23.6 ± 5.8 GBq (n = 3) activity yields of [18F]FMZ were 8.0 ± 1 GBq (n = 3). The synthesis was successfully reproduced at two independent sites, where the product passed quality control release criteria in line with the European Pharmacopoeia standards and ICH Q3D(R1) guidelines to be suitable for human use. Conclusion Reported is a fully automated cassette-based synthesis of [18F]FMZ that is Good Manufacturing Practice (GMP) compatible and produces multi-patient doses of [18F]FMZ

Methodological approach for evaluating the geo-exchange potential: VIGOR Project

In the framework of VIGOR Project, a national project coordinated by the Institute of Geosciences and Earth Resources (CNR-IGG) and sponsored by the Ministry of Economic Development (MiSE), dedicated to the evaluation of geothermal potential in the regions of the Convergence Objective in Italy (Puglia, Calabria, Campania and Sicily), is expected to evaluate the ability of the territory to heat exchange with the ground for air conditioning of buildings. To identify the conditions for the development of low enthalpy geothermal systems collected and organized on a regional scale geological and stratigraphic data useful for the preparation of a specific thematic mapping, able to represent in a synergistic and simplified way the physical parameters (geological, lithostratigraphic, hydrogeological, thermodynamic) that most influence the subsoil behavior for thermal exchange. The litho-stratigraphic and hydrogeological database created for every region led to the production of different cartographic thematic maps, such as the thermal conductivity (lithological and stratigraphical), the surface geothermal flux, the average annual temperature of air, the climate zoning, the areas of hydrogeological restrictions. To obtain a single representation of the geo-exchange potential of the region, the different thematic maps described must be combined together by means of an algorithm, defined on the basis of the SINTACS methodology. The purpose is to weigh the contributions of the involved parameters and to produce a preliminary synthesis map able to identify the territorial use of geothermal heat pump systems, based on the geological characteristics and in agreement with the existing regulatory constraints

Reliability assessment of ultrasound muscle echogenicity in patients with rheumatic diseases: Results of a multicenter international web-based study

ObjectivesTo investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases.MethodsForty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0–3) and a continuous quantitative measurement (“VAS echogenicity,” 0–100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall’s Tau and Pearson’s Rho coefficients.ResultsThe semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57–0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68–0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. “VAS echogenicity” showed a high reliability both in the inter-observer [ICC = 0.80 (0.75–0.85)] and intra-observer [ICC = 0.88 (0.88–0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and “VAS echogenicity” [ICC = 0.52 (0.50–0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively).ConclusionThe results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases