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Introduction: Total body irradiation (TBI) is an important component of the conditioning regimen in patients undergoing hematopoietic stem cell transplants. TBI is used in very few patients and therefore it is generally delivered with standard linear accelerators (LINACs) and not with dedicated devices. Severe pulmonary toxicity is the most common adverse effect after TBI, and patient-specific lead blocks are used to reduce mean lung dose. In this context, online treatment setup is crucial to achieve precise positioning of the lung blocks. Therefore, in this study we aim to report our experience at generating 3D-printed patient-specific lung blocks and coupling a dedicated couch (with an integrated onboard image device) with a modern LINAC for TBI treatment. Material and methods: TBI was planned and delivered (2Gy/fraction given twice a day, over 3 days) to 15 patients. Online images, to be compared with planned digitally reconstructed radiographies, were acquired with the couch-dedicated Electronic Portal Imaging Device (EPID) panel and imported in the iView software using a homemade Graphical User Interface (GUI). In vivo dosimetry, using Metal-Oxide Field-Effect Transistors (MOSFETs), was used to assess the setup reproducibility in both supine and prone positions. Results: 3D printing of lung blocks was feasible for all planned patients using a stereolithography 3D printer with a build volume of 14.5Ã--14.5Ã--17.5 cm³. The number of required pre-TBI EPID-images generally decreases after the first fraction. In patient-specific quality assurance, the difference between measured and calculated dose was generally<2%. The MOSFET measurements reproducibility along each treatment and patient was 2.7%, in average. Conclusion: The TBI technique was successfully implemented, demonstrating that our approach is feasible, flexible, and cost-effective. The use of 3D-printed patient-specific lung blocks have the potential to personalize TBI treatment and to refine the shape of the blocks before delivery, making them extremely versatile. [ABSTRACT FROM AUTHOR]

Background: The stability of precursors and reagents is of utmost importance for developing a robust radiolabelling method that provides high and constant radiochemical yield and radiochemical purity. While performing the QC of the [68Ga]Ga-PSMA-11 injectable solutions according to Ph. Eur. Monograph that has recently been published, a trend to the instability of the standard PSMA-11, the same used as a precursor for [68Ga]Ga-PSMA-11 radiosynthesis, has been observed. This instability led to the formation of a side product in a time-dependent manner. The formation of this compound, besides making the implementation of the Ph. Eur. analytical method more difficult, negatively influenced the radiochemical yield and the radiochemical purity by increasing gallium-68 in colloidal and ionic forms. Results: The nature of the side product was investigated by adding chelators, such as EDTA, to PSMA-11 solutions and using the combination of UHPLC-HRMS. The results led to the definition of the side product structure, as natFe-PSMA-11, from the combination of the high-affinity chelator HBED-CC, present in the molecule of PSMA-11, and environmental Fe (III). Conclusions: Strategies to reduce the risk of low radiolabeling yields and to increase the stability of the PSMA-11 in an aqueous solution were also discussed. [ABSTRACT FROM AUTHOR]

The number of patients with cardiac implantable electronic devices (CIEDs) requiring radiation therapy (RT) for cancer treatment is increasing. The purpose of this study is to estimate the prevalence, possible predictors, and clinical impact of RT-related CIEDs malfunctions. We retrospectively reviewed the medical records of all pacemaker (PM)/implantable cardioverter-defibrillator (ICD) patients who underwent RT in the last 14 years. One hundred and twenty-seven patients who underwent 150 separate RT courses were analysed (99 with a PM and 27 with an ICD). Of note, 21/127 (16.6%) patients were PM-dependent. Neutron-producing RT was used in 37/139 (26.6%) courses, whereas non-neutron-producing RT was used in 102/139 (73.4%) courses. The cumulative dose (Dmax) delivered to the CIED exceeded 5 Gy only in 2/132 (1.5%) cases. Device malfunctions were observed in 3/150 (2%) RT courses, but none was life-threatening or led to a major clinical event and all were resolved by CIED reprogramming. In all cases, the Dmax delivered to the CIED was < 2 Gy. Two malfunctions occurred in the 37 patients treated with neutron-producing RT (5.4%), and 1 malfunction occurred in the 102 patients treated with non-neutron-producing RT (1%) (p = 0.17). Device relocation from the RT field was performed in 2/127 (1.6%) patients. RT in patients with CIED is substantially safe if performed in an appropriately organized environment, with uncommon CIEDs malfunctions and no major clinical events. Neutron-producing energies, rather than Dmax, seem to increase the risk of malfunctions. Device interrogation on a regular basis is advised to promptly manage CIED malfunctions. [ABSTRACT FROM AUTHOR]

Despite its insufficient availability, Copper-67 is currently attracting much attention for its enormous potential for cancer therapy as theranostic radionuclide. This work aims to accurately measure the unexplored cross section 70Zn(p,x)67Cu in the energy range 45–70 MeV and to evaluate its potential advantages in the case of high-intensity proton beams provided by compact cyclotrons. Thin target foils of enriched 70Zn were manufactured by lamination at the INFN-LNL and irradiated at the ARRONAX facility using the stacked-foils method. A radiochemical procedure for the separation of Cu, Ga and Zn contaminants and the isolation of 67Cu from the irradiated material was developed. The efficiency of the chemical processing was determined for each foil by monitoring the activity of selected tracer radionuclides (61Cu, 66Ga and 69mZn) through γ-spectrometry. Experimental data of the 70Zn(p,x)67Cu, 64Cu, 67Ga, 66Ga, 69mZn, 65Zn cross sections were measured for the first time in the energy range 45–70 MeV and compared with the theoretical results obtained by using the TALYS code. The 67Cu production yield by using enriched 70Zn thick targets was compared with the results obtained by using 68Zn targets in the same irradiation conditions. [ABSTRACT FROM AUTHOR]

In the production of Positron Emission Tomography (PET) nuclides at a medical cyclotron facility Ar ( T = 109.34 m) is produced by the activation of air due to the neutron flux, according to the Ar( n, )Ar reaction. In this work, we describe a relatively inexpensive and readily reproducible methodology of air sampling that can be used for quantification of Ar during the routine production of PET nuclides. We report the results of an extensive measurement campaign in the cyclotron bunker and in the ducts of the ventilation system, before and after final filtering of the extracted air. Air Samples were analyzed using a gamma-ray spectrometry system equipped with HPGe detector, with proper correction of the efficiency calibration to account for the samples density. The results of measurement were then used to evaluate the Total Effective Dose (TED) to the population living in the surrounding areas, due to routine emissions in the operation of the cyclotron. The average Ar saturation yield per one liter of air emitted in the environment resulted to be (0.044 ± 0.007) Bq/(A ⋅ dm3). The maximum value of TED for the critical group of the population, even considering an overestimated workload, was less than 0.19 Sv/year, well below the level of radiological relevance. [ABSTRACT FROM AUTHOR]

Radiation protection (RP) in the use of medical cyclotrons involves many aspects both in the routine use and for the decommissioning of a site. Guidelines for site planning and installation, as well as for RP assessment, are given in international documents; however, the latter typically offer analytic methods of calculation of shielding and materials activation, in approximate or idealised geometry set-ups. The availability of Monte Carlo (MC) codes with accurate up-to-date libraries for transport and interaction of neutrons and charged particles at energies below 250 MeV, together with the continuously increasing power of modern computers, makes the systematic use of simulations with realistic geometries possible, yielding equipment and site-specific evaluation of the source terms, shielding requirements and all quantities relevant to RP at the same time. In this work, the well-known FLUKA MC code was used to simulate different aspects of RP in the use of biomedical accelerators, particularly for the production of medical radioisotopes. In the context of the Young Professionals Award, held at the IRPA 14 conference, only a part of the complete work is presented. In particular, the simulation of the GE PETtrace cyclotron (16.5 MeV) installed at S. Orsola-Malpighi University Hospital evaluated the effective dose distribution around the equipment; the effective number of neutrons produced per incident proton and their spectral distribution; the activation of the structure of the cyclotron and the vault walls; the activation of the ambient air, in particular the production of 41Ar. The simulations were validated, in terms of physical and transport parameters to be used at the energy range of interest, through an extensive measurement campaign of the neutron environmental dose equivalent using a rem-counter and TLD dosemeters. The validated model was then used in the design and the licensing request of a new Positron Emission Tomography facility. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to synthesize and preclinically evaluate an F-PSMA positron emission tomography (PET) tracer. Prostate-specific membrane antigen (PSMA) specificity, biodistribution, and dosimetry in healthy and tumor-bearing mice were determined. Methods: Several conditions for the labeling of F-PSMA-11 via F-AlF-complexation were screened to study the influence of reaction temperature, peptide amount, ethanol volume, and reaction time. After synthesis optimization, biodistribution and dosimetry studies were performed in C57BL6 mice. For proof of PSMA-specificity, mice were implanted with PSMA-negative (PC3) and PSMA-positive (LNCaP) tumors in contralateral flanks. Static and dynamic microPET/computed tomography (CT) imaging was performed. Results: Quantitative labeling yields could be achieved with >97 % radiochemical purity. The F-PSMA-11 uptake was more than 24-fold higher in PSMA-high LNCaP than in PSMA-low PC3 tumors (18.4 ± 3.3 %ID/g and 0.795 ± 0.260 %ID/g, respectively; p < 4.2e-5). Results were confirmed by ex vivo gamma counter analysis of tissues after the last imaging time point. The highest absorbed dose was reported for the kidneys. The maximum effective dose for an administered activity of 200 MBq was 1.72 mSv. Conclusion: F-PSMA-11 using direct labeling of chelate-attached peptide with aluminum-fluoride detected PSMA-expressing tumors with high tumor-to-liver ratios. The kidneys were the dose-limiting organs. Even by applying the most stringent dosimetric calculations, injected activities of up to 0.56 GBq are feasible. [ABSTRACT FROM AUTHOR]

During the operational life of a PET Cyclotron, the concrete walls of the cyclotron vault are activated by the secondary neutron flux interacting with rare earths and metals present in the concrete or in reinforcement bars. For this reason when considering dismantling of such accelerators, the amount of radioactive waste has to be evaluated in advance to identify any critical issues or possible countermeasures to be taken to define an optimum decommissioning strategy. The aim of this work is to define a non-destructivein situmeasurement methodology for a preliminary activation assessment of a cyclotron bunker with no need for core drilling. A very compact, USB-powered, CdZnTe (CZT) detector for gamma-ray spectrometry was used for the activation assessment of the site of installation of a GE PETtrace (16.5 MeV) cyclotron, routinely used in the production of positron-emitting radionuclides. Because of the complexity of measurement geometry, the efficiency calibration of the detector was performed via Monte Carlo (MC) simulations. The detector was accurately modelled using FLUKA, including a 5 cm lead shielding set-up. The MC model of the detector was validated for a wide range of energies and different source geometries, showing discrepancies below 5% for all tested sources. The efficiency curve for wall activation measurements was calculated, allowing a quantitative evaluation of activity concentration. [ABSTRACT FROM PUBLISHER]

This work was aimed at characterizing and validating a very compact, USB-powered, CdZnTe detector for gamma-ray spectrometry applications in radiopharmacy. A GR1 model (by KromekTM, Sedgefield, UK) was utilized. The detector was calibrated in energy and efficiency. Samples of [18F]FDG and [68Ga]-DOTANOC were measured to assess the detector’s suitability in radionuclidic purity measurements. The energy resolution and the efficiency obtained are fully adequate for quality control of positron emission tomography radiopharmaceuticals. Results of [18F]FDG and [68Ga]-DOTANOC samples proved to be comparable to those obtained using high-purity Germanium detectors. The performance of the detector and its very compact size make this type of device an extremely attractive tool for QC applications in radiopharmacy. [ABSTRACT FROM PUBLISHER]

With the ever-increasing number of cyclotron installations, and therefore of the maintenance personnel involved, the possibility of swift, ‘yes or no’ screening for internal contamination becomes a prized asset. The present work presents one such procedure, evolved from an approximate whole body counting technique in widespread use in emergency situations. A detailed analysis of possible pathways for contamination leads to pinpointing the nuclides of interest. Different calibration methods are applied, showing moderate variation among them. The minimum detectable activity of order 1000 Bq is determined. The method proves sensitive enough to exclude significant contamination, or to identify its presence instantly ‘on site’ to prompt further in-depth investigation. [ABSTRACT FROM PUBLISHER]

In this paper, radionuclidic impurities generated during the bombardment of an 20Ne gaseous matrix in the routine production of [18F]-fluorodopa were studied. 18F2 is produced by the GE PETtrace cyclotron capable of accelerating negative deuteron ions to an energy of 8.4 MeV. The materials of the target and of the Havar foil, the stable fluorine added as carrier and the natural isotope composition of neon may interact with deuterons and produce undesired radionuclides. To measure them, a sampling system has been realized. Samples of the irradiated gas have been measured by gamma-ray spectrometry. The results show how the radionuclidic purity obtained is very high after a short time from the end of bombardment (EOB). [ABSTRACT FROM AUTHOR]

MiRNAs are single stranded RNAs of 18-22 nucleotides. They are promising diagnostic and prognostic markers for several pathologies including tumors, neurodegenerative, cardiovascular and autoimmune diseases. In the present work the development and characterization of anti-miRNA radiolabeled probes based on peptide nucleic acids (PNAs) for potential non-invasive molecular imaging in vivo of giant cell arteritis are described. MiR-146a and miR-146b-5p were selected as targets because they have been found up-regulated in this disease. Anti-miR and scramble PNAs were synthesized and linked to carboxyfluorescein or DOTA. DOTA-anti-miR PNAs were then labelled with copper-64 (64Cu) to function as non-invasive molecular imaging tools. The affinity of the probes for the targets was assessed in vitro by circular dichroism and melting temperature. Differential uptake of fluorescein and 64Cu labeled anti-miRNA probes was tested on BCPAP and A549 cell lines, expressing different levels of miR-146a and -146b-5p. The experiments showed that the anti-miR-146a PNAs were more effective than the anti-miR-146b-5p PNAs. Anti-miR-146a PNAs could bind both miR-146a and miR-146b-5p. The uptake of fluorescein and 64Cu labeled anti-miR-146a PNAs was higher than that of the negative control scramble PNAs in miRNA expressing cells in vitro. 64Cu-anti-miR-146a PNAs might be further investigated for non-invasive PET imaging of miR-146 overexpressing diseases. [ABSTRACT FROM AUTHOR]

Technetium-99m (99mTc) is the most used radionuclide worldwide in nuclear medicine for diagnostic imaging procedures. 99mTc is typically extracted from portable generators containing 99Mo, which is produced normally in nuclear reactors as a fission product of highly enriched Uranium material. Due to unexpected outages or planned and unplanned reactor shutdown, significant 99mTc shortages appeared as a problem since 2008 The alternative cyclotron-based approach through the 100Mo(p,2n)99mTc reaction is considered one of the most promising routes for direct 99mTc production in order to mitigate potential 99Mo shortages. The design and manufacturing of appropriate cyclotron targets for the production of significant amounts of a radiopharmaceutical for medical use is a technological challenge. In this work, a novel solid target preparation method was developed, including sputter deposition of a dense, adherent, and non-oxidized Mo target material onto a complex backing plate. The latter included either chemically resistant sapphire or synthetic diamond brazed in vacuum conditions to copper. The target thermo-mechanical stability tests were performed under 15.6 MeV proton energy and different beam intensities, up to the maximum provided by the available GE Healthcare (Chicago, IL, USA) PET trace medical cyclotron. The targets resisted proton beam currents up to 60 µA (corresponding to a heat power density of about 1 kW/cm2) without damage or Mo deposited layer delamination. The chemical stability of the proposed backing materials was proven by gamma-spectroscopy analysis of the solution obtained after the standard dissolution procedure of irradiated targets in H2O2. [ABSTRACT FROM AUTHOR]