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

Author(s):  
Richard Wayne Leggett ◽  
Caleigh Samuels

Abstract 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.

2020 ◽  
Vol 191 (1) ◽  
pp. 39-120
Author(s):  
Scott O Schwahn ◽  
Caleigh E Samuels ◽  
Richard W Leggett

Abstract Inhalation and ingestion dose coefficients for the embryo and fetus from intakes of radionuclides by the mother are provided in the International Commission on Radiological Protection (ICRP) Publication 88 for intake of each of 74 radionuclides. To address the many other possible radionuclides to which workers may be exposed, effective dose coefficients were developed for the embryo/fetus for all additional radionuclides addressed in ICRP Publication 107 with half-life of 10 min or more. The general approach was to use the estimated dose to the mother’s uterus during pregnancy as a scalable proxy for the dose to the embryo/fetus. The set of scaling factors used in the study was derived from analyses of the relationships of the dose to the mother’s uterus and the effective dose to the embryo/fetus for the ~400 cases (considering two intake modes and multiple forms of many of the radionuclides) addressed in Publication 88.


2020 ◽  
Vol 49 (1_suppl) ◽  
pp. 68-76 ◽  
Author(s):  
J.D. Harrison ◽  
J.W. Marsh

The International Commission on Radiological Protection (ICRP) publishes guidance on protection from radon in homes and workplaces, and dose coefficients for use in assessments of exposure for protection purposes. ICRP Publication 126 recommends an upper reference level for exposures in homes and workplaces of 300 Bq m−3. In general, protection can be optimised using measurements of air concentrations directly, without considering radiation doses. However, dose estimates are required for workers when radon is considered as an occupational exposure (e.g. in mines), and for higher exposures in other workplaces (e.g. offices) when the reference level is exceeded persistently. ICRP Publication 137 recommends a dose coefficient of 3 mSv per mJ h m−3 (approximately 10 mSv per working level month) for most circumstances of exposure in workplaces, equivalent to 6.7 nSv per Bq h m−3 using an equilibrium factor of 0.4. Using this dose coefficient, annual exposure of workers to 300 Bq m−3 corresponds to 4 mSv. For comparison, using the same coefficient for exposures in homes, 300 Bq m−3 corresponds to 14 mSv. If circumstances of occupational exposure warrant more detailed consideration and reliable alternative data are available, site-specific doses can be assessed using methodology provided in ICRP Publication 137.


1984 ◽  
Vol 23 (02) ◽  
pp. 87-91 ◽  
Author(s):  
K. Flemming

SummaryIn the beginning of medical radiology, only the benefit of ionizing radiation was obvious, and radiation was handled and applied generously. After late effects had become known, the radiation exposure was reduced to doses following which no such effects were found. Thus, it was assumed that one could obtain an optimal medical benefit without inducing any hazard. Later, due to experimental findings, hypotheses arose (linear dose-effect response, no time factor) which led to the opinion that even low and lowest radiation doses were relevant for the induction of late effects. A radiation fear grew, which was unintentionally strengthened by radiation protection decrees: even for low doses a radiation risk could be calculated. Therefore, it was believed that there could still exist a radiation hazard, and the radiation benefit remained in question. If, however, all presently known facts are considered, one must conclude that large radiation doses are hazardous and low doses are inefficient, whereas lowest doses have a biopositive effect. Ionizing radiation, therefore, may cause both, hazard as well as benefit. Which of the two effects prevails is determined by the level of dose.


1981 ◽  
Vol 46 (03) ◽  
pp. 658-661 ◽  
Author(s):  
C Korninger ◽  
J M Stassen ◽  
D Collen

SummaryThe turnover of highly purified human extrinsic plasminogen activator (EPA) (one- and two-chain form) was studied in rabbits. Following intravenous injection, EPA-activity declined rapidly. The disappearance rate of EPA from the plasma could adequately be described by a single exponential term with a t ½ of approximately 2 min for both the one-chain and two-chain forms of EPA.The clearance and organ distribution of EPA was studied by using 125I-labeled preparations. Following intravenous injection of 125I-1abeled EPA the radioactivity disappeared rapidly from the plasma also with a t ½ of approximately 2 min down to a level of 15 to 20 percent, followed by a small rise of blood radioactivity. Gel filtration of serial samples revealed that the secondary increase of the radioactivity was due to the reappearance of radioactive breakdown products in the blood. Measurement of the organ distribution of 125I at different time intervals revealed that EPA was rapidly accumulated in the liver, followed by a release of degradation products in the blood.Experimental hepatectomy markedly prolonged the half-life of EPA in the blood. Blocking the active site histidine of EPA had no effect on the half-life of EPA in blood nor on the gel filtration patterns of 125I in serial plasma samples.It is concluded that human EPA is rapidly removed from the blood of rabbits by clearance and degradation in the liver. Recognition by the liver does not require a functional active site in the enzyme. Neutralization in plasma by protease inhibitors does not represent a significant pathway of EPA inactivation in vivo.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Vera Höllriegl ◽  
Nina Petoussi-Henss ◽  
Kerstin Hürkamp ◽  
Juan Camilo Ocampo Ramos ◽  
Wei Bo Li

Abstract 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.


1994 ◽  
Vol 57 (9) ◽  
pp. 796-801 ◽  
Author(s):  
LIEVE S. G. VAN POUCKE ◽  
CARLOS H. VAN PETEGHEM

The plasma pharmacokinetics and tissue penetration of sulfathiazole (ST) and sulfamethazine (SM) after intravenous and intramuscular injection in pigs were studied. Following a single intravenous dose of 40 mg ST/kg of bodyweight or 80 mg SM/kg of bodyweight, the plasma ST and SM concentrations were best fitted to a two-compartment model. The areas under the curve were 447 ± 39 and 1485 ± 41 mg/h/L, clearances were 0.090 ± 0.007 and 0.054 ± 0.001 L/kg/h, volumes of distribution were 1.16 ± 0.16 and 0.77 ± 0.06 L/kg, half-lifes in distribution phase were l.18 ± 0.57 and 0.23 ± 0.16 h and half-lifes in eliminations phase were 9.0 ± l.6 and 9.8 ± 0.6 h. When the two compounds were administered simultaneously as a single intravenous injection, the pharmacokinetic parameters for ST were not significantly different. The values for SM show statistical differences for some important parameters: α, β and the AUC0–>∞ were significantly decreased and t1/2α, Vd and CIB were significantly increased. It can be concluded that after a single intravenous injection of 40 mg/kg, sulfathiazole has a high tl/2β resulting in higher tissue concentrations. This half-life, which is higher than what is reported in the literature, is not influenced by the simultaneous presence of sulfamethazine. The tl/2β for sulfamethazine after a single intravenous injection of 80 mg/kg is comparable to the data from the literature and is not influenced by the presence of sulfathiazole. Sulfathiazole and SM were also administered simultaneously as an intramuscular injection to healthy pigs at a dosage of 40 and 80 mg/kg bodyweight. Pharmacokinetic experiments were conducted on three pigs. From this pharmacokinetic study it can be concluded that upon a single intramuscular administration of 40 mg/kg of ST and 80 mg/kg of SM the absolute bioavailability in pigs is 0.92 ± 0.04 for ST and l.01 ± 0.07 for SM. Six pigs received five intramuscular im) injections as a single dose of ST and SM every 24 h for five consecutive days for the residue study. The pigs were slaughtered at different times after the last dose was given and samples were taken from various tissues and organs. Concentrations were determined by a microbiological method and a HPTLC method. No edible tissue contained more than 100 μg/kg of the individual sulfonamides after 10 days of withdrawal. It means that adult animals which have a shorter half-life and thus lower tissue concentrations will certainly meet the economic community EC) maximum residue limits after a 10 days withdrawal period.


1980 ◽  
Vol 49 (6) ◽  
pp. 1091-1098 ◽  
Author(s):  
A. Jobe ◽  
M. Ikegami ◽  
I. Sarton-Miller ◽  
L. Barajas

Surfactant, microsomal, and lamellar body fractions were isolated from the lungs of 5-day-old lambs 0.21-55 h after the intravenous injection of radiolabeled palmitic acid. The specific activities as cpm/mumol phospholipid phosphate of phosphatidylcholine, saturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine were measured. The palmitate-labeled phospholipids disappeared from the lung parenchyma with a half-life of approximately 50 h. The radiolabel disappeared from phosphatidylcholine, saturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine of microsomal fractions with initial half-life values of 4.5, 4.6, 1.9, and 23.9 h, respectively. The labeled phospholipids rapidly appeared in the lamellar body fraction and accumulated in the surfactant of the lambs in a linear fashion for 35 h. The curves for the labeling of surfactant with radiolabeled saturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine were similar to the curve for phosphatidylcholine.


2020 ◽  
Vol 49 (2) ◽  
pp. 11-145
Author(s):  
N. Petoussi-Henss ◽  
D. Satoh ◽  
A. Endo ◽  
K.F. Eckerman ◽  
W.E. Bolch ◽  
...  

1981 ◽  
Vol 88 (3) ◽  
pp. 437-441 ◽  
Author(s):  
T. R. LAMBERT ◽  
J. F. WILSON

The half-life for the disappearance of immunoreactive α-melanotrophin in plasma following intravenous injection of synthetic hormone was measured before and after occlusion of the blood supply to certain organs in the anaesthetized rat. Occlusion of the blood supply to the liver, gut, spleen and pancreas, and of the renal circulation caused non-significant increases in half-life of 2·8 and 10·7% respectively. The importance of peripheral tissues in the clearance of α-melanotrophin was demonstrated by the significant 63·4% increase in half-life caused by occlusion of the blood supply to sections of skeletal muscle, fat and skin.


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