Dosimetric Considerations for Ytterbium-169, Selenium-75, and Iridium-192 Radioisotopes in High-Dose-Rate Endorectal Brachytherapy.

PURPOSE: To investigate differences between prescribed and postimplant calculated dose in 192Ir high-dose-rate endorectal brachytherapy (HDR-EBT) by evaluating dose to clinical target volume (CTV) and organs at risk (OARs) calculated with a Monte Carlo-based dose calculation software, RapidBrachyMC. In addition, dose coverage, conformity, and homogeneity were compared among the radionuclides 192Ir, 75Se, and 169Yb for use in HDR-EBT. METHODS AND MATERIALS: Postimplant dosimetry was evaluated using 23 computed tomography (CT) images from patients treated with HDR-EBT using the 192Ir microSelectron v2 (Elekta AB, Stockholm, Sweden) source and the Intracavitary Mold Applicator Set (Elekta AB, Stockholm, Sweden), which is a flexible applicator capable of fitting a tungsten rod for OAR shielding. Four tissue segmentation schemes were evaluated: (1) TG-43 formalism, (2) materials and nominal densities assigned to contours of foreign objects, (3) materials and nominal densities assigned to contoured organs in addition to foreign objects, and (4) materials specified as in (3) but with voxel mass densities derived from CT Hounsfield units. Clinical plans optimized for 192Ir were used, with the results for 75Se and 169Yb normalized to the D90 of the 192Ir clinical plan. RESULTS: In comparison to segmentation scheme 4, TG-43-based dosimetry overestimates CTV D90 by 6% (P = .00003), rectum D50 by 24% (P = .00003), and pelvic bone D50 by 5% (P = .00003) for 192Ir. For 169Yb, CTV D90 is overestimated by 17% (P = .00003) and rectum D50 by 39% (P = .00003), and pelvic bone D50 is significantly underestimated by 27% (P = .007). Postimplant dosimetry calculations also showed that a 169Yb source would give 20% (P = .00003) lower rectum V60 and 17% (P = .00008) lower rectum D50. CONCLUSIONS: Ignoring high-Z materials in dose calculation contributes to inaccuracies that may lead to suboptimal dose optimization and disagreement between prescribed and calculated dose. This is especially important for low-energy radionuclides. Our results also show that with future magnetic resonance imaging-based treatment planning, loss of CT density data will only affect calculated dose in nonbone OARs by 2% or less and bone OARs by 13% or less across all sources if material composition and nominal mass densities are correctly assigned.

Prevalence of, and predictors of, bile acid diarrhea in outpatients with chronic diarrhea: A follow-up study.

BACKGROUND: 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scanning to rule out bile acid diarrhea (BAD) in patients with chronic diarrhea has a high yield. Our previous study showed that patients with terminal ileal (TI) Crohn's disease, TI resection, or cholecystectomy were highly likely to have an abnormal scan. As a result, we encouraged clinicians to use a therapeutic trial of a bile acid sequestrant in these patients, instead of scanning. This may have reduced diagnostic yield of the test, so we examined this issue, as well as factors predicting an abnormal scan, in a large cohort of patients referred subsequently. METHODS: We retrospectively identified 1,071 consecutive patients with chronic diarrhea undergoing SeHCAT scanning at Leeds Teaching Hospitals Trust from 2012 to 2016. We reviewed electronic patient records to obtain information on presenting gastrointestinal symptoms and any proposed risk factors for BAD. BAD was categorized according to subtype and severity. KEY RESULTS: As expected, indications for scanning changed between 2012 and 2016, with a significant reduction in referrals with TI Crohn's disease or resection year-on-year (P < 0.001). Despite this, 457 (42.7%) patients had BAD and there was no downward trend in yield of SeHCAT during the 5 year period (P = 0.39). Overall, 51.6% had type II BAD, 36.1% type III, and 12.3% type I. BAD was mild in 31.7%, moderate in 34.4%, and severe in 33.9%. In total, 653 (61.0%) patients had no known risk factors, other than chronic diarrhea, but 233 (35.7%) of these individuals had BAD, and in 143 (61.4%), this was moderate or severe. CONCLUSIONS AND INFERENCES: Despite reduced referrals for SeHCAT scanning in those with clear risk factors for BAD, the yield remained > 40%. One-third of those without known risk factors had BAD.

Embryo Microinjection of Selenomethionine Reduces Hatchability and Modifies Oxidant Responsive Gene Expression in Zebrafish.

In previous studies we demonstrated that exposure to selenomethionine (SeMet) causes developmental toxicities in zebrafish (Danio rerio). The objectives of this study were to establish a dose-response relationship for developmental toxicities in zebrafish after embryo microinjection of Se (8, 16 or 32 µg/g dry mass of eggs) in the form of SeMet, and to investigate potential underlying mechanism(s) of SeMet-induced developmental toxicities. A dose-dependent increase in frequencies of mortality and total deformities, and reduced hatchability were observed in zebrafish exposed to excess Se via embryo microinjection. The egg Se concentration causing 20% mortality was then used to investigate transcript abundance of proteins involved in antioxidant protection and methylation. Excess Se exposure modified gene expression of oxidant-responsive transcription factors (nuclear factor erythroid 2-related factor nrf2a and nrf2b), and enzymes involved in cellular methylation (methionine adenosyltransferase mat1a and mat2ab) in zebrafish larvae. Notably, excess Se exposure up-regulated transcript abundance of aryl hydrocarbon receptor 2 (ahr2), a signalling pathway involved in the toxicity of dioxin-related compounds. Our findings suggest that oxidative stress or modification of methylation, or a combination of these mechanisms, might be responsible for Se-induced developmental toxicities in fishes.

Effects of selenium diet on expression of selenoproteins in the lung of the rat.

In the present article the radiotracer techniques have been combined with biochemical separation procedures to investigate the effects of changes in the selenium status on the expression of the selenium-containing proteins in the lung and their subcellular fractions. Subcellular separation of the lung has been achieved by differential ultracentrifugation. The selenium-containing proteins in these compartments have been investigated by labeling of rats in vivo with (75)Se, gel electrophoretic separation of the proteins, and autoradiographic detection of the tracer. In the lung of the selenium-deficient animals, the selenium administered was used predominantly to restore the levels of the selenoproteins, while in the lung of the selenium-sufficient animals most of the selenium retained was incorporated into the glutathione peroxidase. Also, higher activity of this enzyme has been found in the lung of the selenium-sufficient animals. The differences in the specific incorporation of the element in the selenium deficiency into different compounds suggested that there are different metabolic pathways for selenium, strongly dependent on its status.

Bioavailability of selenium from the selenotrisulphide derivative of lipoic acid.

BACKGROUND/PURPOSE: Selenium is a required micronutrient in mammals, needed for the activity of enzymes that contain selenocysteine at their active site. Several isoenzymes of glutathione peroxidase and thioredoxin reductase contain selenocysteine and thus the nutritional status of selenium in tissues can have significant impact on the steady state level of reactive oxygen species. The aims of this study were to evaluate the bioavailability of selenium derived from the selenotrisulfide derivative of lipoic acid (LASe) and determine the ability of this compound to be absorbed into skin. METHODS: Bioavailability of selenium derived from LASe was determined using a keratinocyte cell model (HaCat). Efficiency of utilization of selenium was assessed by following the decrease in the incorporation of radiolabeled selenite (75Se) in the presence of increasing concentration of selenium compounds. Percutaneous absorption of LASe was measured by determining selenium levels in full thickness biopsy of skin using a Yorkshire pig model. RESULTS: LASe was efficiently absorbed topically into pig skin, a good model of human skin. In a keratinocyte cell line LASe was an efficient source of selenium for selenoprotein synthesis, demonstrating that LASe is a good candidate as a topical selenium micronutrient. Both L-selenomethionine and selenate were found to be poor sources of selenium for selenoprotein synthesis in the skin cell model and L-selenomethionine was poorly absorbed into pig skin. CONCLUSION: These results indicate that stable selenotrisulfides, such as LASe, are good candidates for testing as topical selenium supplements.

Avaliação do efeito radioprotetor do selenito de sódio no processo de reparação tecidual em ratos / Evaluation of the radioprotective effect of sodium selenite in the tissue repair process in rats

OBJETIVO: Avaliar a ação radioprotetora do selenito de sódio no processo de reparação tecidual. MATERIAIS E MÉTODOS: Ratos Wistar foram submetidos a procedimento cirúrgico para a realização de ferida na região dorsal. Os animais foram divididos em quatro grupos experimentais: controle, selênio, irradiado e selênio-irradiado. Os grupos selênio e selênio-irradiado receberam 2,0 mg/kg de selenito de sódio, 48 horas após a cirurgia. Os grupos irradiado e selênio-irradiado foram submetidos à irradiação em dose única de 6 Gy, administrada somente nas bordas das feridas. Após 4, 7, 13 e 21 dias do procedimento cirúrgico, os animais foram sacrificados e avaliados por meio de análise morfológica, histoquímica e birrefringência do tecido. RESULTADOS: O aspecto estrutural e morfológico, assim como a qualidade do tecido e sua maturação através da quantidade e disposição dos feixes de fibras colágenas, juntamente com o seu grau de orientação macromolecular, permitiu observar a presença de intenso retardo provocado pela irradiação, bem como o efeito radioprotetor do selenito de sódio no processo de reparação. CONCLUSÃO: Dentro das condições experimentais utilizadas, o selenito de sódio apresentou-se como radioprotetor eficaz, visto que o processo de reparação no grupo selênio-irradiado comportou-se, histologicamente, semelhante ao grupo controle.

OBJECTIVE: To evaluate the radioprotective effect of sodium selenite in the tissue repair process. MATERIALS AND METHODS: Male Wistar rats submitted to a surgical procedure to produce a wound in the dorsal region. These animals were then divided in four experimental groups: control, selenium, irradiated and selenium-irradiated. The selenium and selenium-irradiated groups received sodium selenite (2.0 mg/kg), 48 hours after surgery. The irradiated and selenium-irradiated groups received a single dose of 6 Gy, administered only in the borders of the wound. The animals were sacrificed after 4, 7, 13 and 21 days after surgery and morphological, histochemical and tissue birefringence analyses were performed. RESULTS: The structural and morphologic aspects, as well as the quality and maturation of the tissue assessed by the amount, arrangement and molecular orientation of the collagen fibers, showed a marked delay in wound healing caused by radiation and that sodium selenite has a radioprotective effect on the tissue repair process. CONCLUSION: The present study showed that sodium selenite is an efficient radioprotector given the fact that tissue repair process in the selenium-irradiated group was histologically similar to the control group.

Stable isotope-enriched selenite and selenate tracers for human metabolic studies: a fast and accurate method for their preparation from elemental selenium and their identification and quantification using hydride generation atomic absorption spectrometry.

Stable isotope tracers are safe and nutritionally relevant tools for the investigation of mineral metabolism in man. Increased research into the functional role of selenium has resulted in a need for well-characterised, isotopically enriched solutions of the element in order to determine the nutritional relevance of selenium fortification of foods. A simple method for the conversion of isotopically enriched elemental selenium (2.5-10 mg) into selenite and selenate, and their accurate characterisation and quantification is described. Analysis of selenite and selenate tracers using continuous-flow hydride generation-atomic absorption spectrometry technique was based on the specificity of the selenium hydride reaction and allowed their precise (RSD<2.5%) and accurate determination in aqueous solutions. The detection and determination limits were at 0.13 and 0.36 microg Se/l, respectively. Isotopically enriched elemental selenium was converted into selenite and selenate by a nitric acid and a combined nitric acid/hydrogen peroxide oxidation, respectively. The conversion was quantitative (>95%) and specific for both inorganic selenocompounds. Selenite and selenate labels were stable in 0.1 mol/l nitric acid for at least 18 months, i.e. making them ideally suitable for use in long-term metabolic studies. An overview of data relating to the absorption and retention of selenium by humans obtained using the two, well-characterised, tracers is presented and indicates that selenite and selenate are equally well retained in adult men and infants, despite differences in their absorption and urinary excretion characteristics.

Age-dependent variation of selenium-75 biokinetics in rat.

Substantial levels of selenium-79 (79Se) in radioactive waste from the nuclear fuel cycle, may result in a significant collective dose commitment following release into the environment. Few data are available from which the effective dose equivalent among subgroups of the general population can be made. Accordingly, whole body retention and organ content were studied in neonate, adult and pregnant rat following oral contamination with 75Se. The results for whole-body retention conformed to a two-component exponential with terminal biological half-time of about 40, 30 and 20 days in adult male, neonate and pregnant rat, respectively. The highest concentrations of Se occurred in the liver, kidney, and testis. Influence of Se kinetics as a function of age and physiological development on dose estimates are discussed. Results were consistent with current dosimetric models but suggested that the testis should also be included.