Radiobiological model for β-emitter radiopharmaceutical therapy in dynamic cell cultures in the framework of the ISOLPHARM project

In medical physics and radiobiology, the most common method to probe the efficacy of radiation therapy approaches in vitro is the cell survival trial. Recently, the traditional procedure for external beams has been extended by some groups to targeted radionuclides. In parallel, the bioengineering state of the art allows for the use of 3D tissue-mimicking scaffolds to obtain realistic cell cultures in dynamic conditions. The aim of this study is to implement a mathematical model for the assessment of β-emitting radiopharmaceuticals, considering their molecular kinetics in vitro and how it affects the radiation delivery to cells. The molecular transitions will be assumed to fulfill the definition of Markov processes, while the cell survival will depend on the DNA damage, in competition with a logistic growth. The solutions of the resulting differential system will be evaluated by means of numerical examples. This work belongs to the framework of the ISOLPHARM project, headed by INFN-LNL, which has the aim of developing innovative radiopharmaceuticals exploiting the Isotope Separation On-Line (ISOL) at the SPES facility

Monte Carlo based dosimetry using PET/CT and SPECT/CT imaging in radiopharmaceutical therapy in the context of the ISOLPHARM project

The ISOLPHARM project has the aim of producing a set of innovative, high specific activity, carrier-free radioisotopes for target radionuclide therapy exploiting the ISOL technique at the SPES facility of INFN-LNL. The success of a particular radiopharmaceutical cancer treatment relies on an accurate assessment of the tissue response and toxicity. Since biological effects are mediated by the absorbed dose, which is defined as the energy absorbed per unit mass of tissue, internal dosimetry is of funda- mental importance because it allows for the maximization of the therapeutic effect while minimizing the radiation burden to other organs. This thesis work consists in the calculation of internal absorbed dose, following radiopharmaceutical treatments — e.g. with 18 F, 111 In or 111 Ag — by means of different Monte Carlo based approaches (using the Geant4 software) coupled with PET/CT and SPECT/CT images of mice acquired by the ISOLPHARM group. Il progetto ISOLPHARM nasce con lo scopo di produrre una serie di radioisotopi innovativi per l’utilizzo in terapia radiofarmaceutica sfruttando la tecnica ISOL nella facility SPES di INFN-LNL. Il successo di un trattamento radiofarmaceutico su un tumore dipende da un’accurata valutazione della risposta del tessuto e della tossicità. Poiché gli effetti biologici sono mediati dalla dose assorbita, definita come energia assorbita per unità di massa del tessuto, la dosimetria interna è d’importanza fondamentale per permettere la massimizzazione dell’effetto terapeutico minimizzando l’irraggiamento degli altri organi. Il lavoro di tesi consiste nel calcolo della dose assorbita internamente a seguito di trattamenti radiofarmaceutici — per esempio con 18 F, 111 In o 111 Ag — avvalendosi di diversi approcci basati sul metodo Monte Carlo (utilizzando il software Geant4) abbinato a immagini PET/CT o SPECT/CT murine acquisite dal gruppo ISOLPHARM

Radiobiological model for β-emitter radiopharmaceutical therapy in dynamic cell cultures in the framework of the ISOLPHARM project

In medical physics and radiobiology, the most common method to probe the efficacy of radiation therapy approaches in vitro is the cell survival trial. Recently, the traditional procedure for external beams has been extended by some groups to targeted radionuclides. In parallel, the bioengineering state of the art allows for the use of 3D tissue-mimicking scaffolds to obtain realistic cell cultures in dynamic conditions. The aim of this study is to implement a mathematical model for the assessment of β-emitting radiopharmaceuticals, considering their molecular kinetics in vitro and how it affects the radiation delivery to cells. The molecular transitions will be assumed to fulfill the definition of Markov processes, while the cell survival will depend on the DNA damage, in competition with a logistic growth. The solutions of the resulting differential system will be evaluated by means of numerical examples. This work belongs to the framework of the ISOLPHARM project, headed by INFN-LNL, which has the aim of developing innovative radiopharmaceuticals exploiting the Isotope Separation On-Line (ISOL) at the SPES facility

Resonant Laser Ionization and Fine-Structure Study of Silver in an Ablation Plume

We report on a laser photo-ionization study of silver in relation to the Selective Production of Exotic Species (SPES) project at INFN-LNL in the offline laser laboratory. In this study, two dye lasers and an ablation laser operating at 10 Hz are used alongside a time-of-flight mass spectrometer (TOF-MS). Isotopic separation of the natural, stable isotopes 107Ag and 109Ag was clearly observed in the TOF signal. Resonant photo-ionization of silver was achieved with the use of the scheme 4d105s 2S1/2→ 4d105p 2Po3/2→ 4d106d 2D3/2 with transition wavelengths of 328.163 nm and 421.402 nm, respectively. Doppler-suppressed spectroscopy of these transition lines was performed in an ablation plume. Doppler broadening with collinear injection of excitation lasers and the effect of the linewidths of the excitation lasers were investigated. The fine-structure splitting of the level 4d106d 2D (J = 5/2 and J = 3/2) was confirmed to be 186 ± 2 pm, corresponding to 314 ± 3 GHz

Liver injury due to amoxicillin vs. amoxicillin/clavulanate: a subgroupnalysis of a drug-induced liver injury case-control study in Italy

Several studies showed that amoxicillin plus clavulanic acid (co-amoxiclav) is one of the most common agents associated to serious Drug Induced Liver Injury (DILI). We estimated the risk of acute serious DILI associated with amoxicillin alone compared with co-amoxiclav, through a multicenter case-control study carried out in nine Italian hospitals from October 2010 to January 2014.Cases were adults, with a diagnosis of acute liver injury. Controls presented acute clinical disorders, not related to chronic conditions and not involving the liver. Adjusted Odds Ratio (ORs) with 95% CI were calculated initially with a bivariate and then multivariate analysis. We analysed 179 cases matched to 1770 controls. Seven cases were exposed to amoxicillin (adjusted OR 1.69, 95% CI 0.72-3.98) and 22 cases to co-amoxiclav (adjusted OR 3.00, 95% CI 1.76-5.40). Co-amoxiclav almost doubled the risk of serious acute liver injury compared to amoxicillin alone. The incidence of co-amoxiclav induced DILI is very low but the widespread use of this drug by the general population makes the risk clinically relevant. The often inappropriate prescription of antimicrobial agents, and in particular of co-amoxiclav, could expose a given patient to a life-threatening risk compared to a negligible clinical benefit

Sigh in patients with acute hypoxemic respiratory failure and acute respiratory distress syndrome: the PROTECTION pilot randomized clinical trial

Background: Sigh is a cyclic brief recruitment manoeuvre: previous physiological studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity and increase release of surfactant. Research question: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? Study design and methods: We conducted a multi-center non-inferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or acute respiratory distress syndrome undergoing PSV. Patients were randomized to the No Sigh group and treated by PSV alone, or to the Sigh group, treated by PSV plus sigh (increase of airway pressure to 30 cmH2Ofor 3 seconds once per minute) until day 28 or death or successful spontaneous breathing trial. The primary endpoint of the study was feasibility, assessed as non-inferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiological parameters in the first week from randomization, 28-day mortality and ventilator-free days. Results: Two-hundred fifty-eight patients (31% women; median age 65 [54-75] years) were enrolled. In the Sigh group, 23% of patients failed to remain on assisted ventilation vs. 30% in the No Sigh group (absolute difference -7%, 95%CI -18% to 4%; p=0.015 for non-inferiority). Adverse events occurred in 12% vs. 13% in Sigh vs. No Sigh (p=0.852). Oxygenation was improved while tidal volume, respiratory rate and corrected minute ventilation were lower over the first 7 days from randomization in Sigh vs. No Sigh. There was no significant difference in terms of mortality (16% vs. 21%, p=0.342) and ventilator-free days (22 [7-26] vs. 22 [3-25] days, p=0.300) for Sigh vs. No Sigh. Interpretation: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk

Studio dell'attività dei radionuclidi prodotti nel bersaglio SPES-ISOLPHARM

Il lavoro di tesi si inserisce nell'ambito del progetto ISOLPHARM in corso ai Laboratori Nazionali di Legnaro (LNL) dell'Istituto Nazionale di Fisica Nucleare (INFN), volto alla produzione di radiofarmaci sfruttando la tecnica ISOL, e in particolare di ISOLPHARM\_Ag, che si propone di studiare il radioisotopo Ag-111 come possibile radiofarmaco innovativo. Una volta studiata la catena di decadimenti che genera l'Ag-111, si elabora a partire da delle simulazioni Monte Carlo un modello analitico e computazionale in grado di calcolare l'evoluzione temporale dei prodotti del bersaglio primario di carburo di uranio e, successivamente, della composizione del bersaglio secondario al variare del tempo di funzionamento, dell'energia e dell'intensità del fascio di protoni incidente. Infine, si tenta di applicare il modello al Cs-136, radioisotopo già impiegato in fisica medica e prodotto sempre irraggiando il carburo di uranio

Ion-implantation and Annealing of Fe For Semiinsulating Layers Formation In Inp

We investigated the Fe ion implantation and annealing processes used to obtain semi-insulating buried layers in InP epitaxial structures for current confinement in laser device applications. SIMS and RBS-channeling were used as analytical tools. The results show that the annealing is a rather complicated process when the implant causes sample amorphization: high surface reactivity, anomalous dopant diffusion and segregation at damage sites together with inhomogeneous lattice reconstruction are observed

Coronary Plaque in Athletes

The relationship between vigorous physical activity (PA) and the development of coronary atherosclerosis has remained less explored for many years. Recently, literature data have focused on coronary atherosclerosis in athletes showing that prevalence is not trivial, that there are differences among various types of sport, and that there are some peculiar features. As a matter of fact, plaque composition in athletes seems to be characterized by calcium rather than soft components. Specific mechanisms through which vigorous PA influences coronary artery disease are not yet fully understood. However, the prevalent calcific nature of coronary plaques in athletes could be related with a trend in a lower cardiovascular event rate