A revised compartmental model for biokinetics and dosimetry of 2-[18F]FDG.

BACKGROUND: The aim was to review available biokinetic data, collect own experimental data, and propose an updated compartmental model for 2-[18F]FDG in the frame of the revision of the ICRP report on dose coefficients for radiopharmaceuticals used in diagnostic nuclear medicine. METHODS: The compartmental model was developed based on published biokinetic data for 2-[18F]FDG. Additional data on urinary excretion in 23 patients (11 males, 12 females) undergoing whole-body PET/CT examinations were obtained within this study. The unknown biokinetic model parameters were derived using the software SAAM II and verified with a modified version of IDAC-Iodide. Dose coefficients for reference adults were calculated with the programme IDAC-Dose 2.1. A dynamic bladder model was employed for urinary bladder dosimetry. RESULTS: The proposed model consists of following compartments: blood, heart wall, brain, liver, lungs, pancreas, spleen, kidneys, urinary bladder content and a generic pool compartment "Other". The latter was introduced to account for 2-[18F]FDG in body organ and tissues besides the explicitly modelled ones. The model predictions showed a good agreement with experimental data. Urinary bladder wall received the highest absorbed dose coefficient of 7.5E-02 mGy/MBq under the assumption of initial urine volume of 100 ml, first voiding at 45 min p.i. and 3.75 h voiding intervals thereafter. The effective dose coefficient calculated according to the current dosimetry framework of ICRP amounted to 1.7E-02 mSv/MBq, compared to 1.9E-02 mSv/MBq in ICRP Publication 128. CONCLUSION: A compartmental model for 2-[18F]FDG was proposed and will be used to replace the descriptive biokinetic model of ICRP Publication 128. The revised model and the provided dose coefficients are expected to improve reference dosimetry for patients administered with 2-[18F]FDG.

IDAC-Bio, A Software for Internal Dosimetry Based on the New ICRP Biokinetic Models and Specific Absorbed Fractions.

ABSTRACT: Radiation dosimetry is central to virtually all radiation safety applications, optimization, and research. It relates to various individuals and population groups and to miscellaneous exposure situations-including planned, existing, and emergency situations. The International Commission on Radiological Protection (ICRP) has developed a new computational framework for internal dose estimations. Important components are more detailed and improved anatomical models and more realistic biokinetic models than before. The ICRP is currently producing new organ dose and effective dose coefficients for occupational intakes of radionuclides (OIR) and environmental intakes of radionuclides (EIR), which supersede the earlier dose coefficients in Publication 68 and the Publication 72 series, respectively. However, the ICRP only publishes dose coefficients for a single acute intake of a radionuclide and for an integration period of 50 years for intake by adults and to age 70 years for intakes by pre-adults. The new software, IDAC-Bio, performs committed absorbed dose and effective dose calculations for a selectable intake scenario, e.g., for a continuous intake or an intake during x hours per day and y days per week, and for any selected integration time. The software uses the primary data and models of the ICRP biokinetic models and numerically solves the biokinetic model and calculates the absorbed doses to organs and tissues in the ICRP reference human phantoms. The software calculates absorbed dose using the nuclear decay data in ICRP publication 107. IDAC-Bio is a further development and an important addition to the internal dosimetry program IDAC-Dose2.1. The results generated by the software were validated against published ICRP dose coefficients. The potential of the software is illustrated by dose calculations for a nuclear power plant worker who had been exposed to varying levels of 60 Co and who had undergone repeated whole-body measurements, and for a hypothetical member of the public subject to future releases of 148 Gd from neutron spallation in tungsten at the European Spallation Source.

Spatial and temporal variations of 14C in Fucus spp. in Swedish coastal waters.

Carbon-14 (14C) dominates the collective effective dose from globally dispersed long-lived radionuclides produced by and released from the nuclear power industry. Literature data on the discharge of 14C to the marine environment from nuclear power plants (NPPs) and its dispersion in the marine ecosystem are sparse. The local marine 14C background must be determined before the 14C enrichment in the marine environment from a NPP can be estimated. This is not trivial since marine activity concentrations of 14C vary spatially, partly due to long-range transport of 14C from other anthropogenic sources. We have analysed 14C in samples of several species of brown algae (Fucus spp.) collected at 45 sites along the Swedish coast in 2020. At sites remote from NPPs, the 14C activity concentrations per unit mass of carbon (here expressed as Fraction Modern, F14C) were significantly higher on the west coast than on the east coast (F14C up to about 1.10 in Skagerrak, and about 1.01, close to atmospheric levels, in the Baltic Sea and the Gulf of Bothnia). On the west coast, F14C showed a strong correlation with salinity, both of which increased towards the north. This indicates that 14C is carried from other anthropogenic sources (e.g. from the nuclear fuel reprocessing plants at La Hague and Sellafield). The highest value of F14C observed was close to the Ringhals NPP on the west coast, F14C ≈ 1.3, which is higher than expected in the terrestrial environment of this NPP. We also report on temporal variations of F14C in Fucus spp. collected at Särdal on the Swedish west coast during the period 1967-2020. The values of F14C in the Särdal marine samples collected after the 1990s are clearly higher than F14C in clean air CO2, indicating contributions of 14C of anthropogenic origin.

Human Atherosclerotic Plaque Progression Is Dependent on Apoptosis According to Bomb-Pulse 14C Dating.

Individuals with rapidly progressing atherosclerotic plaques are at higher risk of experiencing acute complications. Currently, we lack knowledge regarding factors in human plaque that cause rapid progression. Using the 14C bomb-pulse dating method, we assessed the physical age of atherosclerotic plaques and which biological processes were associated with rapidly progressing plaques. Interestingly, increased apoptosis was the main component associated with a young physical plaque age, reflecting rapid plaque progression. Our findings in combination with recent advances in imaging techniques could guide future diagnostic imaging strategies to identify rapidly progressing plaques or therapeutic targets, halting plaque progression.

IMPROVED AGE- AND GENDER-SPECIFIC RADIATION RISK MODELS APPLIED ON COHORTS OF SWEDISH PATIENTS.

The aim of this study is to implement lifetime attributable risk (LAR) predictions for radiation induced cancers for Swedish cohorts of patients of various age and sex, undergoing diagnostic investigations by nuclear medicine methods. METHODS: Calculations are performed on Swedish groups of patients with Paget's disease and with bone metastases from prostatic cancer and diagnosed with bone scintigraphy with an administration of 500 MBq 99mTc-phosphonate. RESULTS: The inclusion of patient survival rates into the calculations lowers the induced radiation cancer risk, as it takes into account that cohorts of patients have shorter predicted survival times than the general population. CONCLUSION: LAR estimations could be valuable for referring physicians, nuclear medicine physicians, nurses, medical physicists, radiologists, and oncologists and as well as ethical committees for risk estimates for specific subgroups of patients. Caution is however advised with respect to application of LAR predictions to individuals (because of individual sensitivities, circumstances, etc.).

X-RAY AND MOLECULAR IMAGING DURING PREGNANCY AND BREASTFEEDING-WHEN SHOULD WE BE WORRIED?

Some of the ethically most sensitive issues in radiation protection arise at imaging of pregnant-and potentially pregnant-patients and of newborn. This article reviews the current literature and recommendations on imaging during pregnancy and breastfeeding. Risks related to alternative non-ionizing radiation methods are also considered. With few exceptions, exposure of the fetus through radiography, computed tomography (CT) and nuclear medicine imaging can be limited to safe levels, although studies such as abdominal-pelvic CT cannot avoid significant exposure to fetuses. Eight to 10 weeks post-conception, the fetus has a thyroid which starts to concentrate iodide having crossed the placenta barrier resulting in unacceptably high doses to the fetal thyroid after administration of 131I- and even 123I-iodide and other radiopharmaceuticals with a high content of free radioiodine. Many radiopharmaceuticals are excreted through breast milk. Breastfeeding interruption recommendations should be followed to keep the effective dose to the infant below 1 mSv.

Improved Patient Dosimetry at Radioiodine Therapy by Combining the ICRP Compartment Model and the EANM Pre-Therapeutic Standard Procedure for Benign Thyroid Diseases.

Radioactive iodine is commonly used for the treatment of different thyroid conditions since the 1940s. The EANM has developed a standard pre-therapeutic procedure to estimate patient specific thyroid uptake at treatment of benign thyroid diseases. The procedure which models the time dependent fractional thyroid uptake is based on a two-compartment fitting system, one representing the thyroid and the other the blood. The absorbed dose is however only estimated for the thyroid and not for any other organ in the body. A more detailed biokinetic model for iodine is given by the ICRP and includes an iodide transport in the whole body. The ICRP model has 30 different compartments and 48 transfer coefficients to model the biokinetics of iodide and to model different transfer for inorganic iodide and organic iodine. The ICRP model is a recirculation iodine model, and the optimization is performed on the whole model and not exclusively on the thyroid as in the EANM procedure. Combining the EANM method and the ICRP model gives both patient specific estimations of thyroid uptake and retention and include most organs in the body. The new software gives both an improved patient specific dosimetry for the thyroid and an estimation of the absorbed dose to non-target organs and tissues like kidneys, urinary bladder, stomach wall, and uterus. Using the method described in this paper, the repercussions on the daily routines will be minimal.

Construction and evaluation of a real-time personal dosemeter based on a Si sensor for eye-dose measurement.

The objective was to design a thin, flex card based personal dosemeter with low angular and energy dependence. It is based on silicon diodes that can measure the personal dose equivalent. Anisotropic conducting adhesive was used to connect the Si sensor to the flex card. Its intended use is for interventional radiology and after nuclear or radiological accidents, as it provides immediate detailed information about the dose rate to the wearer during shorter periods and integrates the dose rate during hours. It can be freely placed all over the body. By placing the dosemeter close to the eyes, it may be possible to estimate the personal dose equivalent as well as the dose at the lens of the eye.

Optically stimulated luminescence (OSL) dosimetry in irradiated alumina substrates from mobile phone resistors.

In this study the dosimetric properties of alumina (Al2O3) substrates found in resistors retrieved from mobile phones were investigated. Measurements of the decline of optically stimulated luminescence (OSL) generated following exposure of these substrates to ionising radiation showed that 16% of the signal could still be detected after 2 years (735 days). Further, the magnitude of the regenerative dose (calibration dose; D i) had no impact on the accuracy of dose estimates. Therefore, it is recommended that the D i be set as low as is practicable, so as to accelerate data retrieval. The critical dose, D CL, and dose limit of detection, D DL, taking into account the uncertainty in the dose-response relation as well as the uncertainty in the background signal, was estimated to be 7 and 13 mGy, respectively, 1 h after exposure. It is concluded that given the significant long-term component of fading, an absorbed dose of 0.5 Gy might still be detectable up to 6 years after the exposure. Thus, OSL from alumina substrates can be used for dosimetry for time periods far in excess of those previously thought.

IDAC-Dose 2.1, an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms.

BACKGROUND: To date, the estimated radiation-absorbed dose to organs and tissues in patients undergoing diagnostic examinations in nuclear medicine is derived via calculations based on models of the human body and the biokinetic behaviour of the radiopharmaceutical. An internal dosimetry computer program, IDAC-Dose2.1, was developed based on the International Commission on Radiological Protection (ICRP)-specific absorbed fractions and computational framework of internal dose assessment given for reference adults in ICRP Publication 133. The program uses the radionuclide decay database of ICRP Publication 107 and considers 83 different source regions irradiating 47 target tissues, defining the effective dose as presented in ICRP Publications 60 and 103. The computer program was validated against another ICRP dosimetry program, Dose and Risk Calculation (DCAL), that employs the same computational framework in evaluation of occupational and environmental intakes of radionuclides. IDAC-Dose2.1 has a sub-module for absorbed dose calculations in spherical structures of different volumes and composition; this sub-module is intended for absorbed dose estimates in radiopharmaceutical therapy. For nine specific alpha emitters, the absorbed dose contribution from their decay products is also included in the committed absorbed dose calculations. RESULTS: The absorbed doses and effective dose of 131I-iodide determined by IDAC-Dose2.1 were validated against the dosimetry program DCAL, showing identical results. IDAC-Dose2.1 was used to calculate absorbed doses for intravenously administered 18F-FDG and orally administered 99mTc-pertechnetate and 131I-iodide, three frequently used radiopharmaceuticals. Using the tissue weighting factors from ICRP Publication 103, the effective dose per administered activity was estimated to be 0.016 mSv/MBq for 18F-FDG, 0.014 mSv/MBq for 99mTc-pertechnetate, and 16 mSv/MBq for 131I-iodide. CONCLUSIONS: The internal dosimetry program IDAC-Dose2.1 was developed and applied to three radiopharmaceuticals for validation against DCAL and to generate improved absorbed dose estimations for diagnostic nuclear medicine using specific absorbed fraction values of the ICRP computational voxel phantoms. The sub-module for absorbed dose calculations in spherical structures 1 mm to 9 cm in diameter and different tissue composition was included to broaden the clinical usefulness of the program. The IDAC-Dose2.1 program is free software for research and available for download at http://www.idac-dose.org .

Lifetime attributable risk as an alternative to effective dose to describe the risk of cancer for patients in diagnostic and therapeutic nuclear medicine.

The aim of this study is to implement lifetime attributable risk (LAR) predictions of cancer for patients of various age and gender, undergoing diagnostic investigations or treatments in nuclear medicine and to compare the outcome with a population risk estimate using effective dose and the International Commission on Radiological Protection risk coefficients. The radiation induced risk of cancer occurrence (incidence) or death from four nuclear medicine procedures are estimated for both male and female between 0 and 120 years. Estimations of cancer risk are performed using recommended administered activities for two diagnostic (18F-FDG and 99mTc-phosphonate complex) and two therapeutic (131I-iodide and 223Ra-dichloride) radiopharmaceuticals to illustrate the use of cancer risk estimations in nuclear medicine. For 18F-FDG, the cancer incidence for a male of 5, 25, 50 and 75 years at exposure is 0.0021, 0.0010, 0.0008 and 0.0003, respectively. For 99mTc phosphonates complex the corresponding values are 0.000 59, 0.000 34, 0.000 27 and 0.000 13, respectively. For an 131I-iodide treatment with 3.7 GBq and 1% uptake 24 h after administration, the cancer incidence for a male of 25, 50 and 75 years at exposure is 0.041, 0.029 and 0.012, respectively. For 223Ra-dichloride with an administration of 21.9 MBq the cancer incidence for a male of 25, 50 and 75 years is 0.31, 0.21 and 0.09, respectively. The LAR estimations are more suitable in health care situations involving individual patients or specific groups of patients than the health detriment based on effective dose, which represents a population average. The detriment consideration in effective dose adjusts the cancer incidence for suffering of non-lethal cancers while LAR predicts morbidity (incidence) or mortality (cancer). The advantages of these LARs are that they are gender and age specific, allowing risk estimations for specific patients or subgroups thus better representing individuals in health care than effective dose.

The influence of 134Cs on the 137Cs gamma-spectrometric peak-to-valley ratio and improvement of the peak-to-valley method by limiting the detector field of view.

The peak-to-valley method was investigated under laboratory conditions and in situ with respect to both 134Cs perturbation of the 137Cs valley and use of collimation. The 134Cs perturbation is significant down to 134Cs:137Cs activity ratios of 1:100. In these cases the full energy peaks from 134Cs (796 and 802keV) and associated valley should be used instead of the peak and valley from the 137Cs 662keV peak. Use of collimators in situ outside Fukushima Daiichi significantly increased PTV for 134Cs.

A biokinetic and dosimetric model for ionic indium in humans.

This paper reviews biokinetic data for ionic indium, and proposes a biokinetic model for systemic indium in adult humans. The development of parameter values focuses on human data and indium in the form of ionic indium(III), as indium chloride and indium arsenide. The model presented for systemic indium is defined by five different pools: plasma, bone marrow, liver, kidneys and other soft tissues. The model is based on two subsystems: one corresponding to indium bound to transferrin and one where indium is transported back to the plasma, binds to red blood cell transferrin and is then excreted through the kidneys to the urinary bladder. Absorbed doses to several organs and the effective dose are calculated for 111In- and 113mIn-ions. The proposed biokinetic model is compared with previously published biokinetic indium models published by the ICRP. The absorbed doses are calculated using the ICRP/ICRU adult reference phantoms and the effective dose is estimated according to ICRP Publication 103. The effective doses for 111In and 113mIn are 0.25 mSv MBq-1 and 0.013 mSv MBq-1 respectively. The updated biokinetic and dosimetric models presented in this paper take into account human data and new animal data, which represent more detailed and presumably more accurate dosimetric data than that underlying previous models for indium.

Peak-to-valley ratios for three different HPGe detectors for the assessment of 137Cs deposition on the ground and the impact of the detector field-of-view.

The peak-to-valley (PTV) method was investigated experimentally comparing PTV ratios for three HPGe detectors, with complementary Monte Carlo simulations of scatter in air for larger source-detector distances. The measured PTV ratios for 137Cs in air were similar for three different detectors for incident angles between 0 and 90°. The study indicated that the PTV method can differentiate between surface and shallow depth sources if the detector field of view is limited to a radius of less than 3.5m.

SILICON DIODE AS AN ALPHA PARTICLE DETECTOR AND SPECTROMETER FOR DIRECT FIELD MEASUREMENTS.

A windowless silicon (Si) diode (4 mm(2)) was evaluated as alpha particle detector and spectrometer for field measurements. It was irradiated with alpha particles from a (241)Am (2.3 kBq) and a (210)Po (9 kBq) source at source-detector distances (SDD) of 0.5, 1.0 and 1.8 cm. The energy resolution in terms of full width at half maximum was 281, 148 and 113 keV for SDD of 0.5, 1.0 and 1.8 cm, respectively. The minimum detectable activity increased from 0.08 to 0.83 Bq when the SDD increased from 0.5 to 1.8 cm. The detector has the potential for several alpha spectrometric applications, such as monitoring for wound, skin and surface contamination at nuclear fuel facilities, nuclear power plants and facilities handling radioactive waste. Other areas are environmental surveys following releases of actinides at accidents in nuclear power plants and in connection with other radiological or nuclear scenarios.

NEED FOR INDIVIDUAL CANCER RISK ESTIMATES IN X-RAY AND NUCLEAR MEDICINE IMAGING.

To facilitate the justification of an X-ray or nuclear medicine investigation and for informing patients, it is desirable that the individual patient's radiation dose and potential cancer risk can be prospectively assessed and documented. The current dose-reporting is based on effective dose, which ignores body size and does not reflect the strong dependence of risk on the age at exposure. Risk estimations should better be done through individual organ dose assessments, which need careful exposure characterisation as well as anatomical description of the individual patient. In nuclear medicine, reference biokinetic models should also be replaced with models describing individual physiological states and biokinetics. There is a need to adjust population-based cancer risk estimates to the possible risk of leukaemia and solid tumours for the individual depending on age and gender. The article summarises reasons for individual cancer risk estimates and gives examples of methods and results of such estimates.

ORGAN DOSES AND EFFECTIVE DOSE FOR FIVE PET RADIOPHARMACEUTICALS.

Diagnostic investigations with positron-emitting radiopharmaceuticals are dominated by (18)F-fluorodeoxyglucose ((18)F-FDG), but other radiopharmaceuticals are also commercially available or under development. Five of them, which are all clinically important, are (18)F-fluoride, (18)F-fluoroethyltyrosine ((18)F-FET), (18)F-deoxyfluorothymidine ((18)F-FLT), (18)F-fluorocholine ((18)F-choline) and (11)C-raclopride. To estimate the potential risk of stochastic effects (mainly lethal cancer) to a population, organ doses and effective dose values were updated for all five radiopharmaceuticals. Dose calculations were performed using the computer program IDAC2.0, which bases its calculations on the ICRP/ICRU adult reference voxel phantoms and the tissue weighting factors from ICRP publication 103. The biokinetic models were taken from ICRP publication 128. For organ doses, there are substantial changes. The only significant change in effective dose compared with previous estimations was a 46 % reduction for (18)F-fluoride. The estimated effective dose in mSv MBq(-1) was 1.5E-02 for (18)F-FET, 1.5E-02 for (18)F-FLT, 2.0E-02 for (18)F-choline, 9.0E-03 for (18)F-fluoride and 4.4E-03 for (11)C-raclopride.

Excretion of radionuclides in human breast milk after nuclear medicine examinations. Biokinetic and dosimetric data and recommendations on breastfeeding interruption.

PURPOSE: To review early recommendations and propose guidelines for breastfeeding interruption after administration of radiopharmaceuticals, based on additional biokinetic and dosimetric data. METHODS: Activity concentrations in breast milk from 53 breastfeeding patients were determined. The milk was collected at various times after administration of 16 different radiopharmaceuticals. The fraction of the activity administered to the mother excreted in the breast milk, the absorbed doses to various organs and tissues and the effective dose to the infant were estimated. RESULTS: The fraction of the administered activity excreted per millilitre of milk varied widely from 10(-10) to 10(-3) MBq/MBq administered. For (99m)Tc-labelled radiopharmaceuticals, the total fraction of the administered activity excreted in the milk varied from 0.0057 % for (99m)Tc-labelled red blood cells (RBC) to 19 % for (99m)Tc-pertechnetate. The effective dose to an infant per unit activity administered to the mother ranged from 6.7 × 10(-6) mSv/MBq for (99m)Tc-labelled RBC to 3.6 × 10(-2) mSv/MBq for (99m)Tc-pertechnetate. For the other radiopharmaceuticals, the total fraction of administered activity excreted in the milk varied from 0.018 % ((51)Cr-EDTA) to 48 % ((131)I-NaI). The effective dose ranged from 5.6 × 10(-5) mSvinfant/MBqmother ((51)Cr-EDTA) to 106 mSvinfant/MBqmother ((131)I-NaI). CONCLUSIONS: Based on an effective dose limit of 1 mSv to the infant and a typical administered activity, we recommend cessation of breastfeeding for (131)I-NaI and interruption of feeding for 12 h for (125)I-iodohippurate, (131)I-iodohippurate, (99m)Tc-pertechnetate and (99m)Tc-MAA. During this 12-h period all breast milk should be expressed at least three times and discarded. For the other radiopharmaceuticals included in this study, no interruption of breastfeeding is necessary.