Natural compounds are important precursors for the synthesis of new drugs. The development of novel molecules that are useful for various diseases is the main goal of researchers, especially for the diagnosis and treatment of many diseases. Some pathologies need to be treated with radiopharmaceuticals, and, for this reason, radiopharmaceuticals that use the radiolabeling of natural derivates molecules are arousing more and more interest. Radiopharmaceuticals can be used for both diagnostic and therapeutic purposes depending on the radionuclide. β⁺- and gamma-emitting radionuclides are used for diagnostic use for PET or SPECT imaging techniques, while α- and β⁻-emitting radionuclides are used for in metabolic radiotherapy. Based on these assumptions, the purpose of this review is to highlight the studies carried out in the last ten years, to search for potentially useful radiopharmaceuticals for nuclear medicine that use molecules of natural origin as lead structures. In this context, the main radiolabeled compounds containing natural products as scaffolds are analyzed, in particular curcumin, stilbene, chalcone, and benzofuran. Studies on structural and chemical modifications are emphasized in order to obtain a collection of potential radiopharmaceuticals that exploit the biological properties of molecules of natural origin. The radionuclides used to label these compounds are ⁶⁸Ga, ⁴⁴Sc, ¹⁸F, ⁶⁴Cu, ^99mTc, and ¹²⁵I for diagnostic imaging.

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.