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Hydrogen fuel is gaining particular attention in internal combustion engines. In addition to zero-carbon emissions, major advantages relate to its combustion characteristics, which allow a significant increase in thermal efficiency under ultra-lean operation and with very low NOx levels. The ignition system is one of the main technology enablers, as it determines the capability to control ultra-lean operations, avoid backfire phenomena, and/or reduce the risks of abnormal combustions. The latter results from hydrogen's low ignition energy and it is associated with factors like high-temperature residuals, hot spots, and irregular spark plug discharge. The ACIS gen 2-Barrier Discharge Igniter excels in accelerating the initial flame growth speed by the generation of non-equilibrium low-temperature plasma, a strong ignition promoter for the combined action of kinetic and thermal effects. Moreover, its volumetric discharge facilitates combustion initiation on a wide region, in contrast to the localized ignition of traditional spark systems. In this work we present for the first time, to the best of our knowledge, experimental results showing the performance of a hydrogen engine with a low-temperature plasma discharge. Tests were conducted on a single-cylinder research engine, achieving ultra-lean conditions with cycle-to-cycle variability results below 2.5%. The analysis indicates that the H2-BDI combined solution is capable of accelerating the evolution of the flame front compared to traditional spark plugs, leading to a significant reduction in the cycle-to-cycle variability. A meticulous adjustment of the BDI control parameters further enhances igniter performance and contributes to a deeper understanding of the innovative approach proposed in this study. [ABSTRACT FROM AUTHOR]

Engine research community interest in the Radio-Frequency corona-based ignition systems is currently gaining in importance mainly due to their capability to ensure robust combustion at challenging operating conditions such as very lean mixture and/or high EGR dilution. The benefits of Corona low-temperature plasma foster the early flame development thanks to combustion precursors production and to a more energetic and volumetric discharge, resulting in a larger amount of involved mixture. The corona discharge generates ionizing waves, named streamers, whose temporal and spatial variability in orientation, length and branching can affect the combustion onset and, therefore, the engine cycle-to-cycle variability. In this work, the discharge natural luminosity of a RF corona igniter, characterized by four tips electrodes, was recorded in an optically accessible engine via high-speed camera detection. A preliminary statistical analysis of the spatial and temporal streamer variability was performed by operating in motored conditions. Four different engine speeds and two different loads were explored in order to deeply investigate the streamer behaviour at diverse engine operating conditions. A comparison between a motored and a lean operating condition is also proposed to analyse, at a specific engine speed, the mixture influence on the streamers propagation before the start of the combustion.

Radioimmunotherapy (RIT) is an alternative approach in the treatment of resistant/refractory B-cell non-Hodgkin lymphoma (NHL). We performed a feasibility and toxicity pilot study of escalating activity of 90Y-ibritumomab tiuxetan followed by autologous stem cell transplantation (ASCT). Three activity levels were fixed – 30 MBq/kg (0·8 mCi/kg), 45 MBq/kg (1·2 mCi/kg) and 56 MBq/kg (1·5 mCi/kg) – and 13 patients enrolled. One week before treatment all patients underwent dosimetry. ASCT was performed 13 d after Zevalin® administration. Treatment was well tolerated and all patients engrafted promptly. No differences in terms of haematological toxicities were observed among the three levels, apart from a delayed platelet recovery in heavily pretreated patients receiving 56 MBq/kg. Non-haematologic toxicity was mainly related to infections and liver toxicity. One patient died 4 months after treatment because of hepatitis C virus reactivation. One patient developed a myelodysplastic syndrome 2 years after treatment. In conclusion, high-activity Zevalin® with ASCT is feasible and could be safely delivered in elderly and heavily pretreated NHL patients, including those who previously received high-dose chemotherapy and ASCT. Maximum tolerated dose was not clearly defined according to dosimetry and clinical toxicities, and further studies are needed to confirm the toxicity profile and evaluate efficacy. [ABSTRACT FROM AUTHOR]

A novel biotin-DOTA conjugate (r-BHD: reduced biotinamidohexylamine-DOTA) was investigated in order to provide an efficient pretargeted antibody-guided radioimmunotherapy (PAGRIT®) application. Preclinical and clinical results are described. 90Y and 177Lu were used to label r-BHD. The effect of pH and a wide range of specific activities were studied. Radiolabelled r-BHD was tested for affinity towards avidin and for stability in saline or in human serum with and without ascorbic acid. Pharmacokinetic data were collected and organ biodistribution evaluated in a tumour-bearing pretargeted animal model. A pilot study was performed in a metastatic melanoma patient and dosimetry was estimated. High radiochemical purity (>99%) was routinely achieved with 90Y or 177Lu in sodium acetate buffer (1.0 M, pH 5.0) at a specific activity of 2.6 MBq/nmol. Both 90Y- and 177Lu-r-BHD were also prepared at higher specific activities. Radiolabelled r-BHD was stable up to 96 h in human serum and saline with the addition of ascorbic acid. The structural modifications proposed for the r-BHD stabilised it against enzymatic degradation while retaining high binding affinity for avidin. Renal clearance appeared to be the main route of excretion in animals, and high tumour uptake was observed in the pretargeted animals. The patient study showed a total body clearance of ∼85% in 24 h, with a kidney absorbed dose of 1.5 mGy/MBq. Tumour uptake was rapid and the calculated dose to a 10-mm tumour lesion was ∼12 mGy/MBq. These results indicate that the new biotin-DOTA conjugate may be a suitable candidate for pretargeting trials. [ABSTRACT FROM AUTHOR]

Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues has shown encouraging results in various somatostatin receptor positive tumors. Partial remission rates up to 30% have been documented as well as significant improvements in quality of life and survival. This treatment takes advantage of the high specific binding of the radiolabeled peptide to somatostatin receptors overexpressed by the tumors thus being more effective on the tumor cells with less systemic side-effects. The development of macrocyclic chelators conjugated to peptides made possible the stable binding with various radionuclides. In particular 177Lu features favourable physical characteristics with a half-life of 6.7 days, emission of β- with energy of 0.5 MeV for treatment and γ-emissions suitable for imaging. The present contribution describes the learning process achieved at the European Institute of Oncology (IEO) since the first application of 90Y labeled peptides to the therapy of neuroendocrine tumors back in 1997. Continuous improvements led to the preparation of a safe 177Lu labeled peptide for human use. Our learning curve began with the identification of the optimal characteristics of the isotope paying attention to its chemical purity and specific activity along with the optimization of the parameters involved in the radiolabeling procedure. Also the radiation protection issues have been improved along the years and recently more and more attention has been devoted to the pharmaceutical aspects involved in the preparation. The overall issue of the quality has now been completed by drafting an extensive documentation with the goal to deliver a safe and reliable product to our patients.

Unlabelled: High-dose (90)Y-ibritumomab tiuxetan therapy and associated autologous stem cell transplantation (ASCT) were applied after dosimetry. This paper reports dosimetric findings for 3 different methods, including image corrections and actual organ mass corrections. Our first goal was to identify the most reliable and feasible dosimetric method to be adopted in high-dose therapy with (90)Y-ibritumomab tiuxetan. The second goal was to verify the safety of the prescribed activity and the best timing of stem cell reinfusion., Methods: Twenty-two patients with refractory non-Hodgkin's lymphoma were enrolled into 3 activity groups escalating to 55.5 MBq/kg. A somewhat arbitrary cutoff of 20 Gy to organs (except red marrow) was defined as a safe limit for patient recruitment. ASCT was considered of low risk when the dose to reinfused stem cells was less than 50 mGy. (111)In-Ibritumomab tiuxetan (185 MBq) was administered for dosimetry. Blood samples were collected up to 130 h after injection to derive individual blood clearance rates and red marrow doses. Five whole-body images were acquired up to 7 d after injection. A transmission scan and a low-dose CT scan were also acquired. The conjugate-view technique was used, and images were corrected for background, scatter, and attenuation. Absorbed doses were calculated using the OLINDA/EXM software, adjusting doses for individual organ masses. The biodistribution data were analyzed for dosimetry by the conjugate-view technique using 3 methods. Method A was a patient-specific method applying background, scatter, and attenuation correction, with absorbed doses calculated using the OLINDA/EXM software and doses adjusted for individual organ masses and individually estimated blood volumes. Method B was a reference method using the organ masses of the reference man and woman phantoms. Method C was a simplified method using standard blood and red marrow volumes and no corrections., Results: The medians and ranges (in parentheses) for dose estimates (mGy/MBq) according to method A were 1.7 (0.3-3.5) for lungs, 2.8 (1.8-10.6) for liver, 1.7 (0.6-3.8) for kidneys, 1.9 (0.8-5.0) for spleen, 0.8 (0.4-1.0) for red marrow, and 2.8 (1.3-4.7) for testes. None of patients had to postpone ASCT. Absorbed doses from method B differed from method A by up to 100% for liver, 80% for kidneys, 335% for spleen, and 80% for blood because of differences between standard and actual masses. Compared with method A, method C led to dose overestimates of up to 4-fold for lungs, 2-fold for liver, 5-fold for kidneys, 7-fold for spleen, 2-fold for red marrow, and 2-fold for testes., Conclusion: Patient-specific dosimetry with image correction and mass adjustment is recommended in high-dose (90)Y-ibritumomab tiuxetan therapy, for which liver is the dose-limiting organ. Overly simplified dosimetry may provide inaccurate information on the dose to critical organs, the recommended values of administered activity, and the timing of ASCT.

The synthesis of a new biotin derivative, the (CO) reduced N-aminohexyl biotinamido derivative, designed to be serum biotinidase resistant, and its conjugation to the chelator DOTA through an amide bond at one of the four carboxymethyl chains are described. The (90)Y-labeled conjugate was able to bind avidin at different Av/conjugate molar ratios with good results. The preclinical results indicate that this new biotin-DOTA conjugate is a good candidate for pretargeted diagnosis and therapy of tumors.