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.

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.

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.

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.

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.

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.

A prospective 7-year survey on central venous catheter-related complications at a single pediatric hospital.

The aims of this study were to assess the incidence and risk factors of major central venous catheter (CVC)-related complications in a large cohort of children affected by oncological, hematological, or immunological diseases in a 7-year prospective observational study at a single center. Nine hundred fifteen CVCs were inserted in 748 children for a total period of 307,846 CVC-days. Overall, 298 complications were documented with a complication rate of 0.97/1,000 CVC-days: 105 mechanical complications (dislocations 0.30/1,000 CVC-days, ruptures 0.04/1,000 CVC-days), 174 infections (bloodstream infections 0.46/1,000 CVC-days, tunnel infections 0.10/1,000 CVC-days), and 19 thrombosis (0.06/1,000 CVC-days). Significant risk factors were: diagnosis of acute lymphoblastic leukemia (ALL) and age

68Ga-DOTANOC: biodistribution and dosimetry in patients affected by neuroendocrine tumors.

OBJECTIVES: The aim of this work was the evaluation of biodistribution and radiation dosimetry of (68)Ga-DOTANOC in patients affected by neuroendocrine tumors. MATERIALS AND METHODS: We enrolled nine patients (six male and three female) affected by different types of neuroendocrine tumors (NETs). Each patient underwent four whole body positron emission tomography (PET) scans, respectively, at 5, 20, 60, and 120 min after the intravenous injection of about 185 MBq of (68)Ga-DOTANOC. Blood and urine samples were taken at different time points post injection: respectively, at about 5, 18, 40, 60, and 120 min for blood and every 40-50 min from injection time up to 4 h for urine. The organs involved in the dosimetric evaluations were liver, heart, spleen, kidneys, lungs, pituitary gland, and urinary bladder. Dosimetric evaluations were done using the OLINDA/EXM 1.0 software. RESULTS: A physiological uptake of (68)Ga-DOTANOC was seen in all patients in the pituitary gland, the spleen, the liver, and the urinary tract (kidneys and urinary bladder). Organs with the highest absorbed doses were kidneys (9.0E-02+/-3.2E-02mSv/MBq). The mean effective dose equivalent (EDE) was 2.5E-02+/-4.6E-03 mSv/MBq. DISCUSSION AND CONCLUSIONS: The excretion of the compound was principally via urine, giving dose to the kidney and the urinary bladder wall. As SSTR2 is the most frequently expressed somatostatin receptor and (68)Ga-DOTANOC has high affinity to it, this compound might play an important role in PET oncology in the future. The dosimetric evaluation carried out by our team demonstrated that (68)Ga-DOTANOC delivers a dose to organs comparable to, and even lower than, analogous diagnostic compounds.

Radiolabelling, quality control and radiochemical purity assessment of the Octreotide analogue 68Ga DOTA NOC.

Somatostatin receptors 1-5 are over expressed in neuroendocrine tumours (NETs). 68Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-Octreotide (DOTA NOC), a recent synthesized somatostatin analogue, shows high affinity for those receptors. Herein, modifications of a commercial module for the labelling of DOTA NOC with 68Ga, as well as the assessment of time course of the radiochemical purity variation are described. The evaluation of radiochemical stability was done by two different chromatographic methods: reversed-phase radio HPLC and fast TLC analysis. Labelled compound has been found radiochemically stable within 3h from the end of labelling (EOL) and radiochemical purity was always higher than 99%. After 73 labelling sessions the system showed great reproducibility and high radiochemical yield.

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.

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.

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.

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.

Early pulmonary involvement in systemic sclerosis assessed by technetium-99m-DTPA clearance rate.

UNLABELLED: Systemic sclerosis (SS) is frequently associated with interstitial lung disease, but clinical symptoms and radiologic abnormalities may occur late in the course of the disease. This study investigated early pulmonary involvement by assessing the clearance rate of inhaled 99mTc-diethylenetriaminepentaacetic acid (DTPA). METHODS: Sixteen patients with proved SS, no clinical pulmonary symptoms and normal chest radiogram were prospectively studied. The 99mTc-DTPA clearance rate was calculated as the time to half clearance (T1/2) and compared with values obtained in healthy nonsmokers. RESULTS: Six patients showed abnormally increased clearance (T1/2 < 53 min). Rapid clearance was not correlated to SS disease duration or to abnormal pulmonary function tests. Five of six patients with abnormally increased clearance underwent high-resolution CT, which in all five demonstrated pathologic findings that were suggestive of early interstitial disease. CONCLUSION: These findings indicate that in SS asymptomatic patients may frequently present with abnormal 99mTc-DTPA clearance; 99mTc-DTPA lung scintigraphy may allow early detection of subclinical pulmonary involvement in SS.

Prognostic value of captopril renal scintigraphy in renovascular hypertension.

This study evaluates the prognostic value of captopril renal scintigraphy in hypertensive patients undergoing renal artery revascularization. Preoperative studies of 51 patients were correlated with blood pressure results at 6- and 12-mo follow-up. Captopril-renal scintigraphy was carried out 1 hr after oral administration of 50 mg of captopril, using either 220 MBq of 99mTc-DTPA or 74 MBq of 99mTc-MAG3, followed by a baseline study in case of abnormal results. Evidence of amelioration or normalization in relation to captopril study was considered predictive of blood pressure control following treatment. Blood pressure response was favorable in 37 patients, but failed to show any improvement in 14. The scintigraphic test was positive in 33 patients (15 cured, 17 improved, 1 failed) and negative in 18 (3 cured, 2 improved, 13 failed). Sensitivity and specificity for renovascular hypertension was 86.5% and 93%, respectively. For blood pressure cure and improvement, the test had positive and negative predictive values of 97% and 72%, respectively. A positive preoperative captopril renal scintigraphic result is a strong predictor of hypertension curability by renal artery revascularization.

Essential and non-essential amino acid requirement in injured patients receiving total parenteral nutrition.

The metabolic derangements of injury are known to influence nitrogen (N) requirements whilst less is known about individual amino acid (AA) requirements. This study was designed to investigate prospectively N vs AA requirement in 36 injured patients treated with total parenteral nutrition (TPN). The non-protein caloric input was 30 kcal kg-1 day-1 and three AA solutions were assessed containing the same AAs but in different proportion. Overall N intake was set at 0.35 g N kg-1 day-1 for solution A and B and 0.24 g N kg-1 day-1 for solution C. Solution B was similar to A, both being enriched in branched chain AAs (BCAA: 0.69 g kg-1 day-1 in B compared with 0.55 g kg-1 day-1 in A) while decreased in aromatic and sulphurated forms (1.75 times the normal need). Solution C was designed to maintain a daily input of BCAA similar to A (0.52 g kg-1 day-1) but with the supply of aromatic and sulphurated AA between solutions A and B, the supply of other AAs (lysine, theonine, histidine, arginine, glycine) being dependent on the selected N intake. For all the essential AAs the supply was always greater than normal allowances. Increasing BCAA over 0.55 g kg-1 day-1 did not improve N balance when N intake was 0.35 g kg-1 day-1, whilst nutrition with solution C was unable to maintain N balance. Moreover we found indirect evidence that this N intake, 0.52 g kg-1 day-1 was more sparing than 0.37 g kg-1 day-1 of BCAA.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of hypertensive patients with a solitary kidney using captopril renal scintigraphy with 99Tcm-MAG3.

The study aimed to evaluate the safety and reliability of captopril renal scintigraphy (CRS) for diagnosing functionally significant renal artery stenosis (RAS) in hypertensive patients with a solitary kidney. Radionuclide studies were carried out using 100 MBq 99Tcm-mercaptoacetyl triglycine (MAG3), 1 h after administration of 50 mg captopril, and repeated in baseline condition when abnormalities were observed in the provocative study. Scintigraphic diagnosis of RAS was based on analysis of captopril-induced changes of the radiorenographs. Overall, 12 patients with a solitary kidney were investigated, and scintigraphic results compared to angiographic findings. All five patients with positive CRS showed an RAS > 50%, whereas only one of the seven patients with negative CRS was affected by RAS. A significant fall in mean arterial pressure was recorded after captopril administration (123 +/- 12 mm Hg before versus 108 +/- 11 after), but no serious side effects were observed. Our results demonstrate that captopril-induced modifications of the renogram could effectively be used to diagnose the presence of RAS. Captopril renal scintigraphy may therefore be suggested as a reliable and safe noninvasive approach to evaluate hypertensive patients with a solitary kidney.

Reproducibility of a solid and of a liquid caloric meal for gastric emptying studies.

Simple meals are required for routine scintigraphic gastric emptying studies. We evaluated the reproducibility of a caloric liquid meal (520 kcal) compared to that of a solid meal (638 kcal) in 8 and 11 healthy volunteers, respectively. Gastric emptying rates and half-times were similar in two tests using the same meal, while the methods used to express lag times were not highly reproducible. The emptying rates and half-times of the liquid meal were delayed after the intake of bellafoline. In conclusion, this study demonstrates that: (a) gastric emptying rates and half-times are reproducible parameters for the expression of scintigraphic gastric emptying studies; (b) mathematical methods to express lag times are not highly reproducible; (c) a 500 kcal liquid meal is sensitive to the effects of bellafoline, a drug able to delay gastric emptying. Further clinical evaluation is required to test its applicability in routine studies.