Prostate specific membrane antigen (PSMA) has been the subject of several studies in recent decades as a promising molecular target for prostate cancer (PCa), in fact it is considered an excellent molecular target for both PCa imaging (both for staging and follow-up), by means of PET/CT and for radioligand therapy. Its interesting molecular features have enabled the development of a new diagnostic and therapeutic approach for PCa, called "theranostics." Considering the abundance of PSMA-based probes that have appeared so far in the literature, the present work focuses the attention on radiopharmaceuticals with increasing clinical application, highlighting advantages and disadvantages in terms of different metabolization and excretion processes, pharmacokinetic, binding affinity and variable internalization rate, tumor-to-background ratio, residence times and toxicity profile.

Chronic Obstructive Pulmonary Disease (COPD) is a preventable, treatable, and slowly progressive disease, whose course is aggravated by a periodic worsening of symptoms and lung function lasting for several days. The development of home telemonitoring systems has made possible to collect symptoms and physiological data in electronic records, boosting the development of decision support systems (DSSs). Current DSSs work with physiological measurements collected by means of several measuring and communication devices as well as with symptoms gathered by questionnaires submitted to COPD subjects. However, this contrasts with the advices provided by the World Health Organization and the Global initiative for chronic Obstructive Lung Disease that recommend to avoid invasive or complex daily measurements. For these reasons this manuscript presents a DSS detecting the onset of worrisome events in COPD subjects. It uses the hearth rate and the oxygen saturation, which can be collected via a pulse oximeter. The DSS consists in a binary finite state machine, whose training stage allows a subject specific personalization of the predictive model, triggering warnings, and alarms as the health status evolves over time. The experiments on data collected from 22 COPD patients tele-monitored at home for six months show that the system recognition performance is better than the one achieved by medical experts. Furthermore, the support offered by the system in the decision-making process allows to increase the agreement between the specialists, largely impacting the recognition of the worrisome events.

The preparation of antiblastic and parental drugs should be carried out by ensuring an aseptic condition and minimizing exposure to toxic drugs. The aim of this study is to evaluate the quality and qualification of these features of an automated dispensing system, called PHARMODUCT^®, built by Bioduct s.r.l, part of the Dedalus group. Three antiblastic drugs (cyclophosphamide (powder), 5-fluorouracil and paclitaxel) were used and three preparation and dispensing sessions were carried out for each drug, using PHARMODUCT^®. Some of the infusion bags, prepared for each type of antiblastic, were sent to an external laboratory to perform the quantitative dosage analysis and compare it with the quantitative concentration, set on the automatic dispensing equipment, which was found to meet the acceptance criteria of 10%. In addition, to assess the safety of the process for operator exposure to toxic drugs, the differential pressure value between the main chamber and the clean room was measured to be ˂0 Pa, with an hourly leakage rate of ˂2.5 × 10⁻³ h⁻¹. Media fill tests showed no microbiological growth after a 14-day incubation period. The PHARMODUCT^® system meets the requirements of safety and repeatability for the dispensation of parenteral antiblastic drugs.

Background: The purpose of this work was to demonstrate the ozone efficacy for disinfection of the PHARMODUCT^® automatic dispensing system for antineoplastic preparation, as a guarantee of a higher grade of cleanliness. While the use of ozone gas disinfection is almost consolidated in food and water treatment, there is a lack of scientific data in the pharmaceutical field. The scope of this study was to demonstrate the ozone efficacy for disinfection of the PHARMODUCT^® automatic dispensing system, before starting the antineoplastic preparation, in order to ensure a high degree of cleanliness and, at the same time, to define a biodecontamination procedure that could also be translatable to other automated compounding systems on the market. Methods: Ozone efficacy was determined by calculating the difference (pre-exposure–post-exposure) in CFU counts on the plate. A group of four different ATCC-selected microbial strains were tested using two distinct cycles. The first one was evaluated with an ozone gas concentration of 40 ppm for 40 min; the second cycle increased the concentration to 60 ppm for the same duration. Results: Results showed that exposure to 40 ppm ozone gas led to a 4-log reduction of all tested ATCC strains. In contrast, exposure to 60 ppm ensured a 6-log reduction. Conclusions: The ozone disinfection process, applied to the PHARMODUCT^® system, provides a superior grade of cleanliness compared to the manual disinfection procedure, thus offering insight beyond the current anti-inflammatory and analgesic application of ozone therapy in the medical field.

Introduction: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is an aggressive subtype of breast cancer in which accurate, non-invasive assessment of HER2 expression is critical for the stratification of patients and monitoring of treatment. Immuno-positron emission tomography using monoclonal antibodies radiolabeled with long-lived positron emitters, such as [ ⁸⁹ Zr]zirconium, enables whole-body visualization and quantification of HER2 expression. This study aimed to develop and validate a fully integrated, sequential, and automated cassette-based synthesis process for the production, purification, and radiolabeling of [ ⁸⁹ Zr]Zr-desferrioxamine (DFO)-trastuzumab for potential clinical application. Materials and methods: In this study, [ ⁸⁹ Zr]zirconium was produced via cyclotron irradiation of sintered [ ⁸⁹ Y]yttrium solid targets, followed by purification using a hydroxamate-based solid-phase extraction (SPE) system. The resulting [ ⁸⁹ Zr]Zr(C ₂ O ₄ ) ₂ was used to radiolabel trastuzumab preconjugated with the chelator DFO, and the final radiopharmaceutical was purified via PD-10 size-exclusion chromatography. The automated workflow integrated target dissolution, [ ⁸⁹ Zr]zirconium capture and elution, buffer adjustment, antibody radiolabeling, PD-10 purification, and sterile filtration within a single disposable cassette installed on an AllinOne synthesis module. The principal process parameters investigated were target dissolution time, acid concentration and washing volumes, [ ⁸⁹ Zr]zirconium elution conditions, reaction temperature, reaction time, antibody concentration, and starting activity. Preliminary manual radiolabeling experiments were performed at 37 °C to define the radiolabeling conditions, whereas the subsequent automated radiolabeling reaction was performed at 30 °C for 60 min. Radiochemical purity (RCP) and radiochemical yield (RCY) were evaluated via high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). All steps were integrated into a single-use cassette installed on a commercial synthesis module to minimize manual handling. Results: Target dissolution and SPE purification yielded [ ⁸⁹ Zr]Zr(C ₂ O ₄ ) ₂ with an average recovery of approximately 90% and high radionuclidic purity. In preliminary manual experiments, radiolabeling yields of approximately 90% were obtained after 60 min. In contrast, four subsequent automated production runs using starting activities ranging from 37 to 185 MBq showed isolated radiochemical yields ranging from 65% to 78%. The HPLC radiochemical purity was 100% in all automated production runs, while TLC analysis of the final product showed 99%–100% radiochemical purity. Following PD-10 purification, the final product showed 99%–100% radiochemical purity in TLC and a pH of approximately 7. The automated cassette-based workflow demonstrated reproducible radiochemical purity and reduced direct operator handling of the radioactive material, while the lower isolated automated RCY indicated that activity recovery and fluidic transfer efficiency remain areas for further optimization. Discussion and conclusion: The developed cassette-based system demonstrated the feasibility of integrating [ ⁸⁹ Zr]zirconium target dissolution and purification with subsequent radiolabeling and purification of preconjugated DFO-trastuzumab in a single automated sequence. Although the overall automated RCY was lower than the labeling yields obtained in preliminary manual experiments, the consistently high RCP indicates that the main opportunity for further optimization lies in overall activity recovery and fluidic transfer efficiency rather than in the chemical purity of the final product. This process reduces direct operator handling of radioactive material and provides a standardized platform that may be further developed into a Good Manufacturing Practice–compliant production method for [ ⁸⁹ Zr]-labeled monoclonal antibodies.