Innovative Target for Production of Technetium-99m by Biomedical Cyclotron.

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.

Assessing nuclear medicine practices: a critical evaluation of QUANUM through a quality improvement perspective and its wider relevance.

Quality Management Audits in Nuclear Medicine (QUANUM) is an initiative conceived by the International Atomic Energy Agency to enhance global standards in Nuclear Medicine practices. Acknowledging the intricate regulatory frameworks and the necessity for multidisciplinary collaboration, QUANUM has gained global acceptance, demonstrating widespread implementation and positive impacts on patient care. This manuscript critically evaluates the QUANUM program through the lens of quality improvement (QI), by employing established and validated QI tools. Our analysis identifies areas of conformance, underscores key strengths inherent to QUANUM, and pinpoints further learning opportunities for continuous enhancement. Additionally, we assert that the insights derived from scrutinizing this global project within Nuclear Medicine, have valuable implications for departments aspiring for establishing good quality management systems, thereby contributing to the improvement of patient care.

The relative contribution of photons and positrons to skin dose in the handling of PET radiopharmaceuticals.

BACKGROUND: Despite recommendations to use syringe and vial shields to reduce exposure of the hands of staff when manipulating PET radiopharmaceuticals, operators sometimes prefer to work without shields, believing that the faster handling limits the equivalent dose. The aim of this work is to show that this approach does not properly consider the contribution of positrons to the dose. MATERIALS AND METHODS: Using the Varskin+ code, skin doses were calculated for syringes of various sizes, filled with 18F, 11C or 68Ga solution. Syringes without shielding, or shielded with 2 mm and 10 mm of tungsten were considered. RESULTS: Dose rate values in mSv/s per MBq, averaged on a 1 cm2 surface at a depth of 0.07 mm were calculated for all the above conditions. For example, in the case of 3 mL 18F syringe at 1 mm from the skin, the dose rate without shielding is 1.32E-02 and 8.63E-04 for positrons and photons respectively. For 11C, the corresponding dose rates are 4.70E-02 and 8.90E-04 respectively, and for 68Ga, 8.52E-02 and 9.48E-04. CONCLUSIONS: Our results show that the dose due to positrons is the principal component of skin irradiation, by a factor of 3-100, depending on the conditions. The use of shields for syringes and vials is necessary to avoid unjustified skin exposures, that may challenge dose limits. In our opinion, automatic systems for dispensing and allowing injection with shielded syringes, or automatic injectors, are economically justified and should be adopted in PET.

Assessment of emission data and transmission factors supporting radiation protection in the use of 225Ac.

PURPOSE: 225Ac is the most promising alpha emitter for radiopharmaceutical therapy. Labeling PSMA, it showed to be effective in the treatment of prostate cancer and research is undergoing in order to improve its production capacity. Currently, there are still few data published concerning operational radiation protection in its use, both in clinics and in radiopharmacy, and even some basic data are not readily available. This papers aims to estimate the emission gamma-ray constant of 225Ac when at equilibrium with its descendants, and the transmission factors for a broad beam of the gamma-rays emitted by 225Ac and its descendants. MATERIALS & METHODS: Monte Carlo simulations were performed using FLUKA 4.2, considering firstly the source in air, in absence of any shielding, and secondly by adding an increasing thicknesses of Lead, Concrete or Tungsten. In order to obtain statistically meaningful results, high-statistics simulations were performed by sampling up to 1010 primary decay events. As the shielding thickness increased, an appropriate variance reduction technique (importance biasing) was applied. RESULTS: The specific gamma ray emission constant for 225Ac at equilibrium with descendants resulted (3.26 ± 0.03) × 10-5 mSv/h per 1 MBq at a distance of 100 cm. The transmission factors are presented in detail and data have been appropriately interpolated and fitting parameters are reported. CONCLUSIONS: The attenuation curves show a clear bi-exponential trend: performing shielding calculations by adopting a simple approach based on a single value of Half Value Layer (HVL) or Tenth Value Layer (TVL) cannot provide adequate results. In conclusion, our results may be useful in the design of shielded hot cells or accessories necessary for operational radiation protection.

Radiation Safety and Accidental Radiation Exposures in Nuclear Medicine.

Medical radiation accidents and unintended events may lead to accidental or unintended medical exposure of patients and exposure of staff or the public. Most unintended exposures in nuclear medicine will lead to a small increase in risk; nevertheless, these require investigation and a clinical and dosimetric assessment. Nuclear medicine staff are exposed to radiation emitted directly by radiopharmaceuticals and by patients after administration of radiopharmaceuticals. This is particularly relevant in PET, due to the penetrating 511 keV γ-rays. Dose constraints should be set for planning the exposure of individuals. Staff body doses of 1-25 µSv/GBq are reported for PET imaging, the largest component being from the injection. The preparation and administration of radiopharmaceuticals can lead to high doses to the hands, challenging dose limits for radionuclides such as 90Y and even 18F. The risks of contamination can be minimized by basic precautions, such as carrying out manipulations in purpose-built facilities, wearing protective clothing, especially gloves, and removing contaminated gloves or any skin contamination as quickly as possible. Airborne contamination is a potential problem when handling radioisotopes of iodine or administering radioaerosols. Manipulating radiopharmaceuticals in laminar air flow cabinets, and appropriate premises ventilation are necessary to improve safety levels. Ensuring patient safety and minimizing the risk of incidents require efficient overall quality management. Critical aspects include: the booking process, particularly if qualified medical supervision is not present; administration of radiopharmaceuticals to patients, with the risk of misadministration or extravasation; management of patients' data and images by information technology systems, considering the possibility of misalignment between patient personal data and clinical information. Prevention of possible mistakes in patient identification or in the management of patients with similar names requires particular attention. Appropriate management of pregnant or breast-feeding patients is another important aspect of radiation safety. In radiopharmacy activities, strict quality assurance should be implemented at all operational levels, in addition to adherence to national and international regulations and guidelines. This includes not only administrative aspects, like checking the request/prescription, patient's data and the details of the requested procedure, but also quantitative tests according to national/international pharmacopoeias, and measuring the dispensed activity with a calibrated activity meter prior to administration. In therapy with radionuclides, skin tissue reactions can occur following extravasation, which can result in localized doses of tens of Grays. Other relevant incidents include confusion of products for patients administered at the same time or malfunction of administration devices. Furthermore, errors in internal radiation dosimetry calculations for treatment planning may lead to under or over-treatment. According to literature, proper instructions are fundamental to keep effective dose to caregivers and family members after patient discharge below the Dose constraints. The IAEA Basic Safety Standards require measures to minimize the likelihood of any unintended or accidental medical exposures and reporting any radiation incident. The relative complexity of nuclear medicine practice presents many possibilities for errors. It is therefore important that all activities are performed according to well established procedures, and that all actions are supported by regular quality assurance/QC procedures.

In vivo ¹8F-FDG tumour uptake measurements in small animals using Cerenkov radiation.

PURPOSE: 2-[(18)F]Fluoro-2-deoxy-D-glucose ((18)F-FDG) is a widely used PET radiotracer for the in vivo diagnosis of several diseases such as tumours. The positrons emitted by (18)F-FDG, travelling into tissues faster than the speed of light in the same medium, are responsible for Cerenkov radiation (CR) emission which is prevalently in the visible range. The purpose of this study is to show that CR escaping from tumour tissues of small living animals injected with (18)F-FDG can be detected with optical imaging (OI) techniques using a commercial optical instrument equipped with charge-coupled detectors (CCD). METHODS: The theory behind the Cerenkov light emission and the source depth measurements using CR is first presented. Mice injected with (18)F-FDG or saline solution underwent dynamic OI acquisition and a comparison between images was performed. Multispectral analysis of the radiation was used to estimate the depth of the source of Cerenkov light. Small animal PET images were also acquired in order to compare the (18)F-FDG bio-distribution measured using OI and PET scanner. RESULTS: Cerenkov in vivo whole-body images of tumour-bearing mice and the measurements of the emission spectrum (560-660 nm range) are presented. Brain, kidneys and tumour were identified as a source of visible light in the animal body: the tissue time-activity curves reflected the physiological accumulation of (18)F-FDG in these organs. The identification is confirmed by the comparison between CR and (18)F-FDG images. CONCLUSION: These results will allow the use of conventional OI devices for the in vivo study of glucose metabolism in cancer and the assessment, for example, of anti-cancer drugs. Moreover, this demonstrates that (18)F-FDG can be employed as it is a bimodal tracer for PET and OI techniques.

In vitro thrombogenicity of drug-eluting and bare metal stents.

AIMS: We sought to investigate the thrombogenicity of different DES and BMS in an in vitro system of stent perfusion. MATERIAL AND METHODS: The experimental model consisted of a peristaltic pump connected to 4 parallel silicone tubes in which different stents were deployed. Blood was drawn from healthy volunteers and the amount of stent surfaced-induced thrombus deposition was determined using 125I-fibrinogen. RESULTS: Compared to Resolute, Biomatrix and Vision, Xience was associated with the lowest amount of stent surface-induced thrombus formation, with a significant difference compared to Vision (125I-fibrinogen median value deposition [IQ range]: 50 ng [25-98] versus 560 ng [320-1520], respectively, p < 0.05), but not to other DES. In the second set of experiments Fluoropolymer-coated BMS not eluting drug was associated with a significant 3-fold reduction in 125I-fibrinogen deposition (245 ng [80-300]) compared to Vision (625 ng [320-760], p < 0.05), but a 7-fold increase compared to Xience (35 ng [20-60], p < 0.05). Finally Xience was associated with a significantly greater absorption of albumin compared to BMS. CONCLUSIONS: In an in vitro system of stent perfusion, Xience was associated with the lowest amount of stent surface-induced thrombus formation compared with Resolute, Biomatrix and Vision, with a noted synergistic effect between the fluoropolymer and the drug.

Reliability and reproducibility of N-[11C]methyl-choline and L-(S-methyl-[11C])methionine solid-phase synthesis: a useful and suitable method in clinical practice.

BACKGROUND AND OBJECTIVE: N-[11C]methyl-choline ([11C]choline) and L-(S-methyl-[11C])methionine ([11C]methionine) are PET radiopharmaceuticals which have gained interest as oncological tracers. The increasing demand of these radiopharmaceuticals needs robust methods of synthesis with high and reproducible yield which provide enough activity for multiple patient administration in a short synthesis time. METHODS: Different synthetic approaches have been described in the literature but exhaustive reports on performance and reliability of different methods have not been described yet. RESULTS AND CONCLUSION: In the present study, we demonstrated the reliability and reproducibility of the solid-phase [11C]methylation method for the synthesis of [11C]choline and [11C]methionine as a suitable tool for the routine clinical use.

Radiation emission dose from patients administered 90Y-labelled radiopharmaceuticals: comparison of experimental measurements versus Monte Carlo simulation.

AIM: To estimate the radiation dose delivered from patients injected with yttrium-90 (Y)-labelled tiuxetan (Zevalin) to parents and the general population, comparing different techniques. METHODS: The radiation dose delivered from a group of eight patients injected with Y-Zevalin to treat recurrent lymphoma was measured. The data obtained with the Monte Carlo simulation test were compared with the experimental measurements obtained with an ionization chamber detector and with a crystal NaI(Tl) detector. RESULTS: A good correlation was found between the Monte Carlo simulation test and the ionization chamber detector results: the air kerma dose rate was 4.2+/-0.1 and 4.4+/-0.8 microGy/h, respectively (r=0.9, P<0.01). Moreover, more than 99.7% of the air kerma dose rate measured with the ionization chamber detector was because of the contribution of electrons, whereas the contribution of photons was less than 0.3%. In contrast, the air kerma dose rate measured with the crystal NaI(Tl) detector was significantly lower (0.76+0.12 microGy/h) in comparison with the Monte Carlo simulation test. This underestimation was related to the limited crystal NaI(Tl) detector response to low energy rates at variance with the ionization chamber detector. The effective radiation dose released by patients treated with Y-labelled tiuxetan to parents and the general population was approximately 0.1 mSv per treatment cycle. CONCLUSION: Using the Monte Carlo model as a benchmark to compare the experimental measurements obtained by the two different detectors, we found that the ionizing chamber detector was more accurate than the crystal Na(Tl) detector for measuring the exposure radiation dose delivered from patients administered with Y-labelled radiopharmaceuticals. Moreover, the effective radiation dose released by these patients to their parents and the general population is significantly lower than the value recommended by international reports and regulations.

Assessment of radionuclidic impurities in 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) routine production.

In this paper, radionuclidic impurities generated during the bombardment of [18 O]water in the routine production of 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) were studied. In order to assess such impurities and the efficacy of purification methods through the different steps of the synthesis, samples of the target filters, purification columns, [18 O]water recovered after the synthesis, and the final solution was collected and their activities measured and analyzed by means of a gamma-ray spectrometry system. The data demonstrated that purification methods adopted for the synthesis provide the [18F]FDG radionuclidically pure, as requested by the EU Pharmacopeia.

Modeling of a Cyclotron Target for the Production of 11C with Geant4.

BACKGROUND: In medical cyclotron facilities, 11C is produced according to the 14N(p,α)11C reaction and widely employed in studies of prostate and brain cancers by Positron Emission Tomography. It is known from literature that the 11C-target assembly shows a reduction in efficiency during time, meaning a decrease of activity produced at the end of bombardment. This effect might depend on aspects which are still not completely known. OBJECTIVE: Possible causes of the loss of performance of the 11C-target assembly were addressed by Monte Carlo simulations. METHODS: Geant4 was used to model the 11C-target assembly of a GE PETtrace cyclotron. The physical and transport parameters to be used in the energy range of medical applications were extracted from literature data and 11C routine productions. The Monte Carlo assessment of 11C saturation yield was performed varying several parameters such as the proton energy and the angle of the target assembly with respect to the proton beam. RESULTS: The estimated 11C saturation yield is in agreement with IAEA data at the energy of interest, while it is about 35% greater than the experimental value. A more comprehensive modeling of the target system, including thermodynamic effect, is required. The energy absorbed in the inner layer of the target chamber was up to 46.5 J/mm2 under typical irradiation conditions. CONCLUSION: This study shows that Geant4 is potentially a useful tool to design and optimize targetry for PET radionuclide productions. Tests to choose the Geant4 physics libraries should be performed before using this tool with different energies and materials.

Production of Ga-68 with a General Electric PETtrace cyclotron by liquid target.

PURPOSE: In recent years the use of 68Ga (t1/2 = 67.84 min, ß+: 88.88%) for the labelling of different PET radiopharmaceuticals has significantly increased. This work aims to evaluate the feasibility of the production of 68Ga via the 68Zn(p,n)68Ga reaction by proton irradiation of an enriched zinc solution, using a biomedical cyclotron, in order to satisfy its increasing demand. METHODS: Irradiations of 1.7 Msolution of 68Zn(NO3)2 in 0.2 N HNO3 were conducted with a GE PETtrace cyclotron using a slightly modified version of the liquid target used for the production of fluorine-18. The proton beam energy was degraded to 12 MeV, in order to minimize the production of 67Ga through the68Zn(p,2n)67Ga reaction. The product's activity was measured using a calibrated activity meter and a High Purity Germanium gamma-ray detector. RESULTS: The saturation yield of68Ga amounts to (330 ±â€¯20) MBq/µA, corresponding to a produced activity of68Ga at the EOB of (4.3 ±â€¯0.3) GBq in a typical production run at 46 µA for 32 min. The radionuclidic purity of the68Ga in the final product, after the separation, is within the limits of the European Pharmacopoeia (>99.9%) up to 3 h after the EOB. Radiochemical separation up to a yield not lower than 75% was obtained using an automated purification module. The enriched material recovery efficiency resulted higher than 80-90%. CONCLUSIONS: In summary, this approach provides clinically relevant amounts of68Ga by cyclotron irradiation of a liquid target, as a competitive alternative to the current production through the68Ge/68Ga generators.

Implementation of Quality Systems in Nuclear Medicine: Why It Matters. An Outcome Analysis (Quality Management Audits in Nuclear Medicine Part III).

The International Atomic Energy Agency (IAEA) developed a comprehensive program-Quality Management Audits in Nuclear Medicine (QUANUM). This program covers all aspects of nuclear medicine practices including, but not limited to, clinical practice, management, operations, and services. The QUANUM program, which includes quality standards detailed in relevant checklists, aims at introducing a culture of comprehensive quality audit processes that are patient oriented, systematic, and outcome based. This paper will focus on the impact of the implementation of QUANUM on daily routine practices in audited centers. Thirty-seven centers, which had been externally audited by experts under IAEA auspices at least 1 year earlier, were invited to run an internal audit using the QUANUM checklists. The external audits also served as training in quality management and the use of QUANUM for the local teams, which were responsible of conducting the internal audits. Twenty-five out of the 37 centers provided their internal audit report, which was compared with the previous external audit. The program requires that auditors score each requirement within the QUANUM checklists on a scale of 0-4, where 0-2 means nonconformance and 3-4 means conformance to international regulations and standards on which QUANUM is based. Our analysis covering both general and clinical areas assessed changes on the conformance status on a binary manner and the level of conformance scores. Statistical analysis was performed using nonparametric statistical tests. The evaluation of the general checklists showed a global improvement on both the status and the levels of conformances (P < 0.01). The evaluation of the requirements by checklist also showed a significant improvement in all, with the exception of Hormones and Tumor marker determinations, where changes were not significant. Of the 25 evaluated institutions, 88% (22 of 25) and 92% (23 of 25) improved their status and levels of conformance, respectively. Fifty-five requirements, on average, increased from nonconformance to conformance status. In 8 key areas, the number of improved requirements was well above the average: Administration & Management (checklist 2); Radiation Protection & Safety (checklist 4); General Quality Assurance system (checklist 6); Imaging Equipment Quality Assurance or Quality Control (checklist 7); General Diagnostic (checklist 9); General Therapeutic (checklist 12); Radiopharmacy Level 1 (checklist 14); and Radiopharmacy Level 2 (checklist 15). Analysis of results related to clinical activities showed an overall positive impact on both the status and the level of conformance to international standards. Similar results were obtained for the most frequently performed clinical imaging and therapeutic procedures. Our study shows that the implementation of a comprehensive quality management system through the IAEA QUANUM program has a positive impact on nuclear medicine practices.

In-house cyclotron production of high-purity Tc-99m and Tc-99m radiopharmaceuticals.

In the last years, the technology for producing the important medical radionuclide technetium-99m by cyclotrons has become sufficiently mature to justify its introduction as an alternative source of the starting precursor [99mTc][TcO4]- ubiquitously employed for the production of 99mTc-radiopharmaceuticals in hospitals. These technologies make use almost exclusively of the nuclear reaction 100Mo(p,2n)99mTc that allows direct production of Tc-99m. In this study, it is conjectured that this alternative production route will not replace the current supply chain based on the distribution of 99Mo/99mTc generators, but could become a convenient emergency source of Tc-99m only for in-house hospitals equipped with a conventional, low-energy, medical cyclotron. On this ground, an outline of the essential steps that should be implemented for setting up a hospital radiopharmacy aimed at the occasional production of Tc-99m by a small cyclotron is discussed. These include (1) target production, (2) irradiation conditions, (3) separation/purification procedures, (4) terminal sterilization, (5) quality control, and (6) Mo-100 recovery. To address these issues, a comprehensive technology for cyclotron-production of Tc-99m, developed at the Legnaro National Laboratories of the Italian National Institute of Nuclear Physics (LNL-INFN), will be used as a reference example.

A simple Tracerlab module modification for automated on-column [11C]methylation and [11C]carboxylation.

A modification of commercial [11C]methylation module which can be implemented for both on-column [11C]methylation and [11C]carboxylation in the same automated system is described. This module configuration was applied to the solid-phase synthesis of N-[11C]methyl-choline ([11C]choline) and L-(S-methyl-[11C])methionine ([11C]methionine), using [11C]CH(3)I as methylating agent, as well as to the synthesis of [11C]acetate by [11C]carboxylation with [11C]CO2 of methylmagnesium chloride with high and reproducible radiochemical yields in short reaction time, demonstrating to be a fast and reliable tool for the production of these [11C]radiopharmaceuticals for clinical use.

Radiation Protection Studies for Medical Particle Accelerators using Fluka Monte Carlo Code.

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.

Comprehensive Auditing in Nuclear Medicine Through the International Atomic Energy Agency Quality Management Audits in Nuclear Medicine (QUANUM) Program. Part 1: the QUANUM Program and Methodology.

An effective management system that integrates quality management is essential for a modern nuclear medicine practice. The Nuclear Medicine and Diagnostic Imaging Section of the International Atomic Energy Agency (IAEA) has the mission of supporting nuclear medicine practice in low- and middle-income countries and of helping them introduce it in their health-care system, when not yet present. The experience gathered over several years has shown diversified levels of development and varying degrees of quality of practice, among others because of limited professional networking and limited or no opportunities for exchange of experiences. Those findings triggered the development of a program named Quality Management Audits in Nuclear Medicine (QUANUM), aimed at improving the standards of NM practice in low- and middle-income countries to internationally accepted standards through the introduction of a culture of quality management and systematic auditing programs. QUANUM takes into account the diversity of nuclear medicine services around the world and multidisciplinary contributions to the practice. Those contributions include clinical, technical, radiopharmaceutical, and medical physics procedures. Aspects of radiation safety and patient protection are also integral to the process. Such an approach ensures consistency in providing safe services of superior quality to patients. The level of conformance is assessed using standards based on publications of the IAEA and the International Commission on Radiological Protection, and guidelines from scientific societies such as Society of Nuclear Medicine and Molecular Imaging (SNMMI) and European Association of Nuclear Medicine (EANM). Following QUANUM guidelines and by means of a specific assessment tool developed by the IAEA, auditors, both internal and external, will be able to evaluate the level of conformance. Nonconformances will then be prioritized and recommendations will be provided during an exit briefing. The same tool could then be applied to assess any improvement after corrective actions are taken. This is the first comprehensive audit program in nuclear medicine that helps evaluate managerial aspects, safety of patients and workers, clinical practice, and radiopharmacy, and, above all, keeps them under control all together, with the intention of continuous improvement.

Comprehensive Auditing in Nuclear Medicine Through the International Atomic Energy Agency Quality Management Audits in Nuclear Medicine Program. Part 2: Analysis of Results.

The International Atomic Energy Agency has developed a program, named Quality Management Audits in Nuclear Medicine (QUANUM), to help its Member States to check the status of their nuclear medicine practices and their adherence to international reference standards, covering all aspects of nuclear medicine, including quality assurance/quality control of instrumentation, radiopharmacy (further subdivided into levels 1, 2, and 3, according to complexity of work), radiation safety, clinical applications, as well as managerial aspects. The QUANUM program is based on both internal and external audits and, with specifically developed Excel spreadsheets, it helps assess the level of conformance (LoC) to those previously defined quality standards. According to their level of implementation, the level of conformance to requested standards; 0 (absent) up to 4 (full conformance). Items scored 0, 1, and 2 are considered non-conformance; items scored 3 and 4 are considered conformance. To assess results of the audit missions performed worldwide over the last 8 years, a retrospective analysis has been run on reports from a total of 42 audit missions in 39 centers, three of which had been re-audited. The analysis of all audit reports has shown an overall LoC of 73.9 ± 8.3% (mean ± standard deviation), ranging between 56.6% and 87.9%. The highest LoC has been found in the area of clinical services (83.7% for imaging and 87.9% for therapy), whereas the lowest levels have been found for Radiopharmacy Level 2 (56.6%); Computer Systems and Data Handling (66.6%); and Evaluation of the Quality Management System (67.6%). Prioritization of non-conformances produced a total of 1687 recommendations in the final audit report. Depending on the impact on safety and daily clinical activities, they were further classified as critical (requiring immediate action; n = 276; 16% of the total); major (requiring action in relatively short time, typically from 3 to 6 months; n = 604; 36%); whereas the remaining 807 (48%) were classified as minor, that is, to be addressed whenever possible. The greatest proportion of recommendations has been found in the category "Managerial, Organization and Documentation" (26%); "Staff Radiation Protection and Safety" (17.3%); "Radiopharmaceuticals Preparation, Dispensing and Handling" (15.8%); and "Quality Assurance/Quality Control" and "Management of Equipment and Software" (11.4%). The lowest level of recommendations belongs to the item "Human Resources" (4%). The QUANUM program proved applicable to a wide variety of institutions, from small practices to larger centers with PET/CT and cyclotrons. Clinical services rendered to patients showed a good compliance with international standards, whereas issues related to radiation protection of both staff and patients will require a higher degree of attention. This is a relevant feedback for the International Atomic Energy Agency with regard to the effective translation of safety recommendations into routine practice. Training on drafting and application of standard operating procedures should also be considered a priority.

Assessment of the neutron dose field around a biomedical cyclotron: FLUKA simulation and experimental measurements.

In the planning of a new cyclotron facility, an accurate knowledge of the radiation field around the accelerator is fundamental for the design of shielding, the protection of workers, the general public and the environment. Monte Carlo simulations can be very useful in this process, and their use is constantly increasing. However, few data have been published so far as regards the proper validation of Monte Carlo simulation against experimental measurements, particularly in the energy range of biomedical cyclotrons. In this work a detailed model of an existing installation of a GE PETtrace 16.5MeV cyclotron was developed using FLUKA. An extensive measurement campaign of the neutron ambient dose equivalent H∗(10) in marked positions around the cyclotron was conducted using a neutron rem-counter probe and CR39 neutron detectors. Data from a previous measurement campaign performed by our group using TLDs were also re-evaluated. The FLUKA model was then validated by comparing the results of high-statistics simulations with experimental data. In 10 out of 12 measurement locations, FLUKA simulations were in agreement within uncertainties with all the three different sets of experimental data; in the remaining 2 positions, the agreement was with 2/3 of the measurements. Our work allows to quantitatively validate our FLUKA simulation setup and confirms that Monte Carlo technique can produce accurate results in the energy range of biomedical cyclotrons.