Guidance on prevention of unintended and accidental radiation exposures in nuclear medicine.

Nuclear medicine (NM) procedures for diagnosis and treatment of disease are performed routinely in hospitals throughout the world. These involve preparation and administration to patients of pharmaceuticals labelled with radioactive material. The International Atomic Energy Agency (IAEA) and the World Health Organisation highlighted the need for improvement in prevention of medical radiation incidents and accidents in the Bonn Call-for-Action in 2012. An IAEA Technical Meeting was held on prevention of unintended exposures and accidents in NM in 2018 to address the issue. Exposures can take place at any time when radioactive material is being produced and used, and the risk continues after procedures have been completed. Thus there is potential for staff or members of the general public to be exposed, as well as patients. This paper sets out guidelines for incident prevention based on presentations and discussions at the meeting, and review of reports from the literature. It deals with potential incidents in in-house radionuclide production, radiopharmaceutical preparation, administration to patients, and following a procedure, as well as aspects in management of radioactive materials. Special attention has been paid to therapeutic procedures, as these have the potential to cause more harm to patients from erroneous administrations, including tissue reactions from extravasation of radiopharmaceutical, and could lead to significant contamination events. Administration of NM therapy is generally contraindicated in pregnancy. Identification of any patient who may be pregnant is crucial and it might be necessary to verify this with a pregnancy test for patients within the age band considered to be fertile. Inclusion of NM therapy incidents in the IAEA automated reporting system SAFRON is recommended. In summary, the paper aims to highlight errors that could occur during different phases of NM procedures in order to aid prevention of incidents. The value of periodic audit in evaluating systems in place on a regular basis is emphasised. Approaches to incident investigation and follow-up are described, and the need to ensure corrective action is taken to address any deficiencies stressed.

Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction.

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15-20 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801-3). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E γ > 200 keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7-19.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc.

Spatial variations in trace element concentrations of the sea urchin, Paracentrotus lividus, a first reference study in the Mediterranean Sea.

A study on Trace Elements (TE) from sea urchin gonads has been conducted in the western Mediterranean Sea. Contamination data were used to determine a Trace Method Pollution Index (TEPI). TE concentrations varied considerably depending on the location of the sampling stations. The results showed that five trace elements (Zn, Fe, As, Al, Cu) are ubiquitous. The geographical area considered (Corsica) represents an important range of environmental conditions and types of pressure that can be found in the western Mediterranean Sea. TEPI was used to classify the studied sites according to their degree of contamination and allowed reliable comparison of TE contamination between local and international sites. TE contamination of the western Mediterranean Sea displayed a north-to-south gradient, from the Italian coasts down through the insular Corsican coasts to the north African littoral. Due to the increasing environmental pressure on the Mediterranean Sea, a regular monitoring of TE levels in marine organisms is necessary to prevent any further environmental deterioration.

Trace element concentrations in the apex predator swordfish (Xiphias gladius) from a Mediterranean fishery and risk assessment for consumers.

Swordfish (Xiphias gladius L., 1758) is an apex predator, highly migratory meso-pelagic fish widely distributed in the Atlantic Ocean and Mediterranean. As top predators, this fish may be the end reservoir of the bioaccumulation of trace elements in a food chain because they occupy higher trophic levels and are an important food source, causing them to be potentially hazardous to consume. This study aims to investigate the concentration of 18 trace elements of Swordfish, caught in the Mediterranean Sea and to discuss human exposure risks. The mean element levels in the fish muscles were clearly below the maximum allowable concentrations established by International food safety regulations. The data suggested that the risk is minor and acceptable for human health. The findings of this study amplify the scarce database on contaminants available, especially new data on "emerging elements", for this species from the Mediterranean Sea.

The concept of minimum detectable activity of radionuclide activity meters and their suitability for routine quality control of radiopharmaceuticals. An experimental study.

Radionuclide activity meters ("dose calibrators") are ionization chambers designed to measure relatively high amount of activities which are normally contained in radiopharmaceuticals. However, in the current radiopharmacy practice, these radiation detectors have been proposed to be used in measurements of samples with lower activity, such as in routine quality control (QC) tests. To check the feasibility of such measurements, in this work we assessed the performance of four different devices in the lower range of detectability, by means of experimental measurements of a radioactive sample. Accuracy and precision of each device was evaluated as a function of the activity contained in the sample in order to estimate a threshold value, or minimum detectable activity (MDA), which, according to our operational definition, may be used to express the concept of Limit of Quantification (LoQ). Moreover, a generalized procedure for the estimation of the MDA was established, which, being device- and radionuclide-independent, it may be adopted by every laboratory. Our results showed a significant variability in the MDA achieved by different activity meters. Hence a single QC test may result feasible with one specific instrument, and not with another one. Moreover, feasibility depends also on the confidence level required for each test. For these reasons, each activity meter should be qualified for its MDA or LoQ by each laboratory according to a procedure such as that described in this paper.

Distinct routes to metastasis: plasticity-dependent and plasticity-independent pathways.

The cascade that culminates in macrometastases is thought to be mediated by phenotypic plasticity, including epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT and MET). Although there is substantial support for the role of EMT in driving cancer cell invasion and dissemination, much less is known about the importance of MET in the later steps of metastatic colonization. We created novel reporters, which integrate transcriptional and post-transcriptional regulation, to test whether MET is required for metastasis in multiple in vivo cancer models. In a model of carcinosarcoma, metastasis occurred via an MET-dependent pathway; however, in two prostate carcinoma models, metastatic colonization was MET independent. Our results provide evidence for both MET-dependent and MET-independent metastatic pathways.

Comparison of otolith and scale readings for age and growth estimation of common dentex Dentex dentex.

Three methods of age estimation were compared for Dentex dentex. Based on sectioned otoliths, scales appeared to be relevant only up to 5 years and whole otoliths up to 12 years. The maximum estimated age was 36 years, which constitutes to date the oldest age reported.

Wettability influence on the onset temperature of pool boiling: Experimental evidence onto ultra-smooth surfaces.

In this article we study systematically the effect of wettability on the onset of boiling on the same nanometrically smooth surface. By grafting different monolayers of molecules, we were able to explore the wettability from the equilibrium static contact angle, θ0=0° to θ0=110°, without changing the surface topography. The superheat temperature at the onset of pool boiling was measured and eventually a non-classical trend of TONB as a function of wettability was observed. The nucleation site densities for the different grafting cases were also measured by image analysis. Moreover, we propose a novel theoretical interpretation to this phenomenon linking nucleation and the molecular diffusion coefficient. MD simulation results support this approach.

Monte Carlo modeling provides accurate calibration factors for radionuclide activity meters.

Accurate determination of calibration factors for radionuclide activity meters is crucial for quantitative studies and in the optimization step of radiation protection, as these detectors are widespread in radiopharmacy and nuclear medicine facilities. In this work we developed the Monte Carlo model of a widely used activity meter, using the Geant4 simulation toolkit. More precisely the "PENELOPE" EM physics models were employed. The model was validated by means of several certified sources, traceable to primary activity standards, and other sources locally standardized with spectrometry measurements, plus other experimental tests. Great care was taken in order to accurately reproduce the geometrical details of the gas chamber and the activity sources, each of which is different in shape and enclosed in a unique container. Both relative calibration factors and ionization current obtained with simulations were compared against experimental measurements; further tests were carried out, such as the comparison of the relative response of the chamber for a source placed at different positions. The results showed a satisfactory level of accuracy in the energy range of interest, with the discrepancies lower than 4% for all the tested parameters. This shows that an accurate Monte Carlo modeling of this type of detector is feasible using the low-energy physics models embedded in Geant4. The obtained Monte Carlo model establishes a powerful tool for first instance determination of new calibration factors for non-standard radionuclides, for custom containers, when a reference source is not available. Moreover, the model provides an experimental setup for further research and optimization with regards to materials and geometrical details of the measuring setup, such as the ionization chamber itself or the containers configuration.

Radiation dose around a PET scanner installation: comparison of Monte Carlo simulations, analytical calculations and experimental results.

PURPOSE: Monte Carlo study of radiation transmission around areas surrounding a PET room. METHODS: An extended population of patients administered with (18)F-FDG for PET-CT investigations was studied, collecting air kerma rate and gamma ray spectra measurements at a reference distance. An MC model of the diagnostic room was developed, including the scanner and walls with variable material and thickness. MC simulations were carried out with the widely used code GEANT4. RESULTS: The model was validated by comparing simulated radiation dose values and gamma ray spectra produced by a volumetric source with experimental measurements; ambient doses in the surrounding areas were assessed for different combinations of wall materials and shielding and compared with analytical calculations, based on the AAPM Report 108. In the range 1.5-3.0 times of the product between the linear attenuation coefficient and thickness of an absorber (µ x), it was observed that the effectiveness of different combinations of shielding is roughly equivalent. An extensive tabulation of results is given in the text. CONCLUSIONS: The validation tests performed showed a satisfactory agreement between the simulated and expected results. The simulated dose rates incident on, and transmitted by the walls in our model of PET scanner room, are generally in good agreement with analytical estimates performed using the AAPM Publication No. 108 method. This provides an independent confirmation of AAPM's approach. Even in this specific field of application, GEANT4 proved to be a relevant and accurate tool for dosimetry estimates, shielding evaluation and for general radiation protection use.

Drop rebound after impact: the role of the receding contact angle.

Data from the literature suggest that the rebound of a drop from a surface can be achieved when the wettability is low, i.e., when contact angles, measured at the triple line (solid-liquid-air), are high. However, no clear criterion exists to predict when a drop will rebound from a surface and which is the key wetting parameter to govern drop rebound (e.g., the "equilibrium" contact angle, θeq, the advancing and the receding contact angles, θA and θR, respectively, the contact angle hysteresis, Δθ, or any combination of these parameters). To clarify the conditions for drop rebound, we conducted experimental tests on different dry solid surfaces with variable wettability, from hydrophobic to superhydrophobic surfaces, with advancing contact angles 108° < θA < 169° and receding contact angles 89° < θR < 161°. It was found that the receding contact angle is the key wetting parameter that influences drop rebound, along with surface hydrophobicity: for the investigated impact conditions (drop diameter 2.4 < D0 < 2.6 mm, impact speed 0.8 < V < 4.1 m/s, Weber number 25 < We < 585), rebound was observed only on surfaces with receding contact angles higher than 100°. Also, the drop rebound time decreased by increasing the receding contact angle. It was also shown that in general care must be taken when using statically defined wetting parameters (such as advancing and receding contact angles) to predict the dynamic behavior of a liquid on a solid surface because the dynamics of the phenomenon may affect surface wetting close to the impact point (e.g., as a result of the transition from the Cassie-Baxter to Wenzel state in the case of the so-called superhydrophobic surfaces) and thus affect the drop rebound.

Use of 65Zn as a tracer for the assessment of purification in the 68Ga-DOTANOC synthesis.

In the last years (68)Ga has got into the focus of researchers and clinicians especially for radio-labeling of biomolecules; an important characteristic of this positron emitting isotope is its availability via the (68)Ge/(68)Ga generator system: the long-lived (68)Ge (t1/2=270.8 d) produces the short-lived (68)Ga (t1/2=67.63 min) which decays to stable (68)Zn. (68)Ge breakthrough compromises (68)Ga radionuclidic purity, while (68)Zn might affect the specific activity of the radiopharmaceutical. In this paper we investigated the weight of these impurities in (68)Ga-DOTANOC synthesis. (65)Zn (t1/2=244.26d; decay mode: EC 98.3%, ß(+) 1.7%) was used as a radiotracer of stable (68)Zn; samples of the purification columns, wastes and product were recovered and measured with a calibrated HPGe gamma-ray spectrometry system. The results showed that (68)Zn competes with (68)Ga in labeling DOTANOC with a (95±2)% labeling yield; they also proved the effectiveness of the STRATA X-C cationic post-processing of the generator eluate in lowering the amount of this impurity to less than 1%. Moreover this approach, along with the purification of the final product through a STRATA X cartridge, effectively removes (68)Ge breakthrough providing a (68)Ga-DOTANOC radionuclidic purity of (99.9999986±0.0000006)%, superior to 99.9% required by the Pharmacopoeia Monograph on (68)Ga Edotreotide injection.

Water drops dancing on ice: how sublimation leads to drop rebound.

Drop rebound is a spectacular event that appears after impact on hydrophobic or superhydrophobic surfaces but can also be induced through the so-called Leidenfrost effect. Here we demonstrate that drop rebound can also originate from another physical phenomenon, the solid substrate sublimation. Through drop impact experiments on a superhydrophobic surface, a hot plate, and solid carbon dioxide (commonly known as dry ice), we compare drop rebound based on three different physical mechanisms, which apparently share nothing in common (superhydrophobicity, evaporation, and sublimation), but lead to the same rebound phenomenon in an extremely wide temperature range, from 300 °C down to even below -79 °C. The formation and unprecedented visualization of an air vortex ring around an impacting drop are also reported.

Accurate modeling of a DOI capable small animal PET scanner using GATE.

In this work we developed a Monte Carlo (MC) model of the Sedecal Argus pre-clinical PET scanner, using GATE (Geant4 Application for Tomographic Emission). This is a dual-ring scanner which features DOI compensation by means of two layers of detector crystals (LYSO and GSO). Geometry of detectors and sources, pulses readout and selection of coincidence events were modeled with GATE, while a separate code was developed in order to emulate the processing of digitized data (for example, customized time windows and data flow saturation), the final binning of the lines of response and to reproduce the data output format of the scanner's acquisition software. Validation of the model was performed by modeling several phantoms used in experimental measurements, in order to compare the results of the simulations. Spatial resolution, sensitivity, scatter fraction, count rates and NECR were tested. Moreover, the NEMA NU-4 phantom was modeled in order to check for the image quality yielded by the model. Noise, contrast of cold and hot regions and recovery coefficient were calculated and compared using images of the NEMA phantom acquired with our scanner. The energy spectrum of coincidence events due to the small amount of (176)Lu in LYSO crystals, which was suitably included in our model, was also compared with experimental measurements. Spatial resolution, sensitivity and scatter fraction showed an agreement within 7%. Comparison of the count rates curves resulted satisfactory, being the values within the uncertainties, in the range of activities practically used in research scans. Analysis of the NEMA phantom images also showed a good agreement between simulated and acquired data, within 9% for all the tested parameters. This work shows that basic MC modeling of this kind of system is possible using GATE as a base platform; extension through suitably written customized code allows for an adequate level of accuracy in the results. Our careful validation against experimental data confirms that the developed simulation setup is a useful tool for a wide range of research applications.

Automation synthesis modules review.

The introduction of (68)Ga labelled tracers has changed the diagnostic approach to neuroendocrine tumours and the availability of a reliable, long-lived (68)Ge/(68)Ga generator has been at the bases of the development of (68)Ga radiopharmacy. The huge increase in clinical demand, the impact of regulatory issues and a careful radioprotection of the operators have boosted for extensive automation of the production process. The development of automated systems for (68)Ga radiochemistry, different engineering and software strategies and post-processing of the eluate were discussed along with impact of automation with regulations.

Optical imaging of radioisotopes: a novel multimodal approach to molecular imaging.

In this review there will be presented an overview of the literature about the recent developments on radiotracers imaging using optical methods and their applications. We will begin with a short summary regarding the discovery of Cerenkov radiation (CR) and then focus on the early developments and experimental validation of planar Cerenkov luminescence imaging. A significant improvement in Cerenkov luminescence imaging was given by the development of tomographic methods in order to obtain in vivo whole body 3D images of Cerenkov sources. An interesting and original application discussed in this review is the use of CR as the excitation source of quantum dots and fluorophores. We will also present some recent experimental results on in vivo radio luminescence imaging of alpha and gamma emitters. All these results make optical radioisotopes imaging an interesting cost-effective tool for the screening of new probes for both imaging and therapeutic applications. Other interesting aspects are the uses of Cerenkov radiation for radiotherapy and for radiopharmaceuticals synthesis applications. We will conclude by summarising the most important results and the future challenges.

Effective production of 65Zn with a PET cyclotron.

Cyclotrons dedicated to the production of PET radiopharmaceuticals for clinical use can be a resource also for research in other fields of science. In the present study we assessed the feasibility of (65)Zn production via the (65)Cu(p,n)(65)Zn reaction using a 16.5 MeV GE-PETtrace biomedical cyclotron. The radioisotope (65)Zn (t(1/2)=244.26 zd; decay mode: EC 98.3%, ß(+) 1.7%) has a wide range of applications, especially in botany and agriculture; its long half life allows storage and delivery to research centers without a cyclotron on site. Natural copper foils (thickness: 100 µm; purity: >99.9%) were irradiated in a solid target station developed in our institution. The EXFOR and IAEA cross sections databases were carefully studied to optimize the irradiation setup in order to maximize the yield of the radionuclide of interest and minimize the production of isotopic impurities. We performed production runs at 20 µA for 30 min. Activity was measured using a calibrated HPGe gamma ray detector and an ionization chamber radionuclide activity meter. These measures showed the presence of two main contaminants: (63)Zn (t(1/2)=38.47 min) and (64)Cu (t(1/2)=12.7h); we produced (65)Zn with a saturation yield of (1.06 ± 0.07) GBq/µA (E(p)=12.65→10.48 MeV). The irradiated target was dissolved in 1 ml of 6N HNO(3) at the temperature of 90°C and then purified through anion exchange chromatography with BIO RAD AG 1×8 resin. The radionuclidic purity of the final solution of (65)Zn in HCl 0.005 N, expressed in activity, resulted superior to (99.921 ± 0.003) %.

Measuring therapeutic adherence in systemic lupus erythematosus with electronic monitoring.

OBJECTIVE: We used an electronic monitoring system to quantify adherence to prescribed oral therapies by patients with systemic lupus erythematosus (SLE). METHODS: Participants were included from a larger longitudinal study cohort of 110 patients recruited from publicly-funded rheumatology clinics, 78 of whom agreed to have their SLE drug therapy electronically monitored for two years with the Medication Events Monitoring System (MEMS®, AARDEX Group). Adherence was determined as the percentage of days (weeks for methotrexate) the patient took the medication as prescribed by the physician. Collected data included SLEDAI; SLICC damage index for SLE (SDI); medical outcome study social support survey (MOS-SSS); Center for Epidemiologic Studies depression scale (CESD); and quality of life (SF-12). RESULTS: Ninety percent of the cohort was female, 45% were Hispanic, and 49% were African-American. Mean age was 36.3 years, disease duration was 5.9 years, SLEDAI score was 3.2, and SDI score was 0.9. Adherence was 62% for all drugs combined and did not differ significantly for individual medications. Patients with more depression (p < 0.02), and higher number of pills taken daily (p < 0.02) were more likely to be non-adherent. Only one-fourth of the patients had an average adherence of ≥80%; these patients had a better mental component score (SF-12) at 24 months than non-adherent patients (p < 0.01). CONCLUSIONS: Electronic monitoring demonstrated that only one-fourth of the patients had an adherence rate ≥80%. Polypharmacy and depression were associated with non-adherence.

Influence of the wettability on the boiling onset.

Experimental investigation of pool boiling is conducted in stationary conditions over very smooth bronze surfaces covered by a very thin layer of gold presenting various surface treatments to isolate the role of wettability. We show that even with surfaces presenting mean roughness amplitudes below 10 nm the role of surface topography is of importance. The study shows also that wettability alone can trigger the boiling and that the boiling position on the surface can be controlled by chemical grafting using for instance alkanethiol. Moreover, boiling curves, that is, heat flux versus the surface superheat (which is the difference between the solid surface temperature and the liquid saturation temperature), are recorded and enabled to quantify, for this case, the significant reduction of the superheat at the onset of incipient boiling due to wettability.