Basis for the ICRP’s updated biokinetic model for systemic astatnie

The ICRP recently updated its biokinetic models for workers in a series of reports called the OIR (Occupational Intakes of Radionuclides) series. A new biokinetic model for astatine, the heaviest member of the halogen family, was adopted in OIR Part 5 (ICRP Publication 151, in press). This paper provides an overview of available biokinetic data for astatine; describes the basis for the ICRP’s updated model for astatine; and tabulates dose coefficients for intravenous injection of each of the two longest lived and most important astatine isotopes, 211At and 210At. Astatine-211 (T1/2 = 7.214 h) is a promising radionuclide for use in targeted α-particle therapy due to several favorable properties including its half-life and the absence of progeny that could deliver significant radiation doses outside the region of α-particle therapy. Astatine-210 (T1/2 = 8.1 h) is an impurity generated in the production of 211At in a cyclotron and represents a potential radiation hazard via its long-lived progeny 210Po (T1/2 = 138 d). Tissue dose coefficients for injected 210At and 211At based on the updated model are shown to differ considerably from values based on the ICRP’s previous model for astatine, particularly for the thyroid, stomach wall, salivary glands, lungs, spleen, and kidneys.

Stochastic parametric skeletal dosimetry model for humans: General approach and application to active marrow exposure from bone-seeking beta-particle emitters

The objective of this study is to develop a skeleton model for assessing active marrow dose from bone-seeking beta-emitting radionuclides. This article explains the modeling methodology which accounts for individual variability of the macro- and microstructure of bone tissue. Bone sites with active hematopoiesis are assessed by dividing them into small segments described by simple geometric shapes. Spongiosa, which fills the segments, is modeled as an isotropic three-dimensional grid (framework) of rod-like trabeculae that “run through” the bone marrow. Randomized multiple framework deformations are simulated by changing the positions of the grid nodes and the thickness of the rods. Model grid parameters are selected in accordance with the parameters of spongiosa microstructures taken from the published papers. Stochastic modeling of radiation transport in heterogeneous media simulating the distribution of bone tissue and marrow in each of the segments is performed by Monte Carlo methods. Model output for the human femur at different ages is provided as an example. The uncertainty of dosimetric characteristics associated with individual variability of bone structure was evaluated. An advantage of this methodology for the calculation of doses absorbed in the marrow from bone-seeking radionuclides is that it does not require additional studies of autopsy material. The biokinetic model results will be used in the future to calculate individual doses to members of a cohort exposed to 89,90Sr from liquid radioactive waste discharged to the Techa River by the Mayak Production Association in 1949–1956. Further study of these unique cohorts provides an opportunity to gain more in-depth knowledge about the effects of chronic radiation on the hematopoietic system. In addition, the proposed model can be used to assess the doses to active marrow under any other scenarios of 90Sr and 89Sr intake to humans.

A glikációs index lehetséges magyarázata a hemoglobinglikáció biokinetikus modellje alapján

Összefoglaló. Bevezetés: A HbA1c integrált retrospektív mutatója az elmúlt időszak vércukrának, rendszeres vizsgálata a cukorbetegek anyagcserekontrolljának megítélésében elengedhetetlen. Helyes értékelése azonban nem egyszerű, mert a HbA1c és a vércukor közötti összefüggés nem lineáris. A mérést közvetlenül megelőző hyperglykaemiás epizódok hatása a HbA1c szintjére nagyobb, mint azoké, amelyek régebben történtek. A jelenségre a glikáció biokinetikus modellje ad magyarázatot. Célkitűzés: A mért és a biokinetikus modell alapján számított HbA1c közötti egyezés, illetve diszkordancia vizsgálata. Módszer: A vizsgálatokat 157, 1-es és 2-es típusú cukorbeteg 1793, laboratóriumban mért éhomi vércukor- és 511 HbA1c-adatából végeztük. A különbséget a glikációs index segítségével számítottuk, amely a mért és a számított HbA1c-érték aránya. Eredmények: Egyezést mindössze a vizsgált betegek kevesebb mint egyötödödében találtunk, 60%-ban az index értéke alacsony (<0,95) és 21%-ban magas (>1,05) volt. Az adatok részletes analízise szerint jó anyagcserekontroll esetében gyakoribb a vártnál magasabb, mért HbA1c-érték, mint a biokinetikus egyenlet által számítotté, és rosszabb kontroll (magasabb átlagos vércukor) esetében ez fordítva van. Egyezés esetén a regressziós egyenlet együtthatói gyakorlatilag azonosak a modell alapján számított értékekkel. Következtetés: Vizsgálataink felvetik azt a lehetőséget, hogy a biokinetikus modell magyarázatot adhat a vércukor és a HbA1c közötti diszkordanciára. Orv Hetil. 2021; 162(41): 1652–1657. Summary. Introduction: HbA1c is an integrated retrospective marker of previous blood glucose concentrations and its regular measurement is indispensable in the assessment of glycaemic compensation of diabetic patients. However, its proper interpretation is not simple becasuse the relationship between HbA1c and average glycemia is not a linear one. Hyperglycemic episodes occuring immediately before the measurement have greater impact on the HbA1c level as compared with those taking place earlier. Objective: Assessment of concordance and discordance between measured and according to the biokinetic model calculated values of HbA1c. Method: The calculations were made from averages of 1793 fasting blood glucose and 511 HbA1c of 157, type 1 and 2 diabetic patients. The glycation index is the quotient between measured and calculated HbA1c. Results: Agreement was found in less than one fifth of the 157 patients; in 60% the value of glycation was low (<0.95) and in 21% high (>1.05). Analysis of the glycation index according to the level of glycemic compensation revealed that in patients with good compensation, the measured HbA1c value was more often higher than the expected and in patients with unsatisfactory compensation the opposite was true. Conclusion: These results raise the possibility that the discordance between average glycemia and measured HbA1c can be explained by the biokinetic model. Orv Hetil. 2021; 162(41): 1652–1657.

Radiopharmacokinetic modelling and radiation dose assessment of 223Ra used for treatment of metastatic castration-resistant prostate cancer

Purpose Ra-223 dichloride (223Ra, Xofigo®) is used for treatment of patients suffering from castration-resistant metastatic prostate cancer. The objective of this work was to apply the most recent biokinetic model for radium and its progeny to show their radiopharmacokinetic behaviour. Organ absorbed doses after intravenous injection of 223Ra were estimated and compared to clinical data and data of an earlier modelling study. Methods The most recent systemic biokinetic model of 223Ra and its progeny, developed by the International Commission on Radiological Protection (ICRP), as well as the ICRP human alimentary tract model were applied for the radiopharmacokinetic modelling of Xofigo® biodistribution in patients after bolus administration. Independent kinetics were assumed for the progeny of 223Ra. The time activity curves for 223Ra were modelled and the time integrated activity coefficients, $$ \overset{\sim }{a}\left({r}_S,{T}_D\right), $$ a ~ r S T D , in the source regions for each progeny were determined. For estimating the organ absorbed doses, the Specific Absorbed Fractions (SAF) and dosimetric framework of ICRP were used together with the aforementioned $$ \overset{\sim }{a}\left({r}_S,{T}_D\right) $$ a ~ r S T D values. Results The distribution of 223Ra after injection showed a rapid plasma clearance and a low urinary excretion. Main elimination was via faeces. Bone retention was found to be about 30% at 4 h post-injection. Similar tendencies were observed in clinical trials of other authors. The highest absorbed dose coefficients were found for bone endosteum, liver and red marrow, followed by kidneys and colon. Conclusion The biokinetic modelling of 223Ra and its progeny may help to predict their distributions in patients after administration of Xofigo®. The organ dose coefficients of this work showed some variation to the values reported from clinical studies and an earlier compartmental modelling study. The dose to the bone endosteum was found to be lower by a factor of ca. 3 than previously estimated.

Calculation of Internal Dose and Possible Limits for Intakes of Radionuclides in Case of Plutonium Wounds

Purpose: Assessment of the degree of compliance with the principles of radiation safety and regulatory requirements in case of plutonium wounds. Material and methods: Using a wound intake of plutonium by a worker as an example, issues of the formation of the internal dose due to the wound intake and formal comparison of calculated dose values with regulatory requirements are considered. The calculations are carried out using expert analysis of the experimental data on the urine excretion of plutonium during the observation period of 7 years based on the ICRP model for direct intake into blood. In addition, calculations are carried out using prognostic assessment of the same dose values based on the biokinetic model for radionuclide-contaminated wounds published by NCRP Report No 156 together with the above model of the ICRP for plutonium compounds Strong, Colloids, Particles and Fragment. Results: Based on the calculations, possible annual limits on intakes (ALI) of radionuclides in case of plutonium wounds are derived. As criteria for determining the ALI, dose values were taken that due to the uptake of the radionuclide into the systemic circulation from the wound for any calendar year considered for 50 years after the wound intake of selected plutonium compound. Namely, the committed effective dose; the effective dose implemented in a year and the organ annual equivalent dose (to bone surface and liver). Conclusion: Based on the analysis of the above calculations, the authors formulated the formation features of the employee’s internal exposure due to wound intake of plutonium and recommendations for determining the value of plutonium intake in the wound, evaluating the effectiveness of decorporation therapy and determining the type of radionuclide compound. This allows one to more accurately assess the degree of compliance with regulatory requirements and make an informed decision on the necessary measures of medical intervention and their urgency.