ICRP Publication 140: Radiological Protection in Therapy with Radiopharmaceuticals.

Radiopharmaceuticals are increasingly used for the treatment of various cancers with novel radionuclides, compounds, tracer molecules, and administration techniques. The goal of radiation therapy, including therapy with radiopharmaceuticals, is to optimise the relationship between tumour control probability and potential complications in normal organs and tissues. Essential to this optimisation is the ability to quantify the radiation doses delivered to both tumours and normal tissues. This publication provides an overview of therapeutic procedures and a framework for calculating radiation doses for various treatment approaches. In radiopharmaceutical therapy, the absorbed dose to an organ or tissue is governed by radiopharmaceutical uptake, retention in and clearance from the various organs and tissues of the body, together with radionuclide physical half-life. Biokinetic parameters are determined by direct measurements made using techniques that vary in complexity. For treatment planning, absorbed dose calculations are usually performed prior to therapy using a trace-labelled diagnostic administration, or retrospective dosimetry may be performed on the basis of the activity already administered following each therapeutic administration. Uncertainty analyses provide additional information about sources of bias and random variation and their magnitudes; these analyses show the reliability and quality of absorbed dose calculations. Effective dose can provide an approximate measure of lifetime risk of detriment attributable to the stochastic effects of radiation exposure, principally cancer, but effective dose does not predict future cancer incidence for an individual and does not apply to short-term deterministic effects associated with radiopharmaceutical therapy. Accident prevention in radiation therapy should be an integral part of the design of facilities, equipment, and administration procedures. Minimisation of staff exposures includes consideration of equipment design, proper shielding and handling of sources, and personal protective equipment and tools, as well as education and training to promote awareness and engagement in radiological protection. The decision to hold or release a patient after radiopharmaceutical therapy should account for potential radiation dose to members of the public and carers that may result from residual radioactivity in the patient. In these situations, specific radiological protection guidance should be provided to patients and carers.

New mesh-type phantoms and their dosimetric applications, including emergencies.

Committee 2 of the International Commission on Radiological Protection (ICRP) has constructed mesh-type adult reference computational phantoms by converting the voxel-type ICRP Publication 110 adult reference computational phantoms to a high-quality mesh format, and adding those tissues that were below the image resolution of the voxel phantoms and therefore not included in the Publication 110 phantoms. The new mesh phantoms include all the necessary source and target tissues for effective dose calculations, including the 8-40-µm-thick target layers of the alimentary and respiratory tract organs, thereby obviating the need for supplemental organ-specific stylised models (e.g. respiratory airways, alimentary tract organ walls and stem cell layers, lens of the eye, and skin basal layer). To see the impact of the new mesh-type reference phantoms, dose coefficients for some selected external and internal exposures were calculated and compared with the current reference values in ICRP Publications 116 and 133, which were calculated by employing the Publication 110 phantoms and the supplemental stylised models. The new mesh phantoms were also used to calculate dose coefficients for industrial radiography sources near the body, which can be used to estimate the organ doses of the worker who is accidentally exposed by an industrial radiography source; in these calculations, the mesh phantoms were deformed to reflect the size of the worker, and also to evaluate the effect of posture on dose coefficients.

Computational phantoms, ICRP/ICRU, and further developments.

Phantoms simulating the human body play a central role in radiation dosimetry. The first computational body phantoms were based upon mathematical expressions describing idealised body organs. With the advent of more powerful computers in the 1980s, voxel phantoms have been developed. Being based on three-dimensional images of individuals, they offer a more realistic anatomy. Hence, the International Commission on Radiological Protection (ICRP) decided to construct voxel phantoms representative of the adult Reference Male and Reference Female for the update of organ dose coefficients. Further work on phantom development has focused on phantoms that combine the realism of patient-based voxel phantoms with the flexibility of mathematical phantoms, so-called 'boundary representation' (BREP) phantoms. This phantom type has been chosen for the ICRP family of paediatric reference phantoms. Due to the limited voxel resolution of the adult reference computational phantoms, smaller tissues, such as the lens of the eye, skin, and micron-thick target tissues in the respiratory and alimentary tract regions, could not be segmented properly. In this context, ICRP Committee 2 initiated a research project with the goal of producing replicas of the ICRP Publication 110 phantoms in polygon mesh format, including all source and target regions, even those with micron resolution. BREP phantoms of the fetus and the pregnant female at various stages of gestation complete the phantoms available for radiation protection computations.

Conversion Coefficients for Proton Beams using Standing and Sitting Male Hybrid Computational Phantom Calculated in Idealized Irradiation Geometries.

The aim of this study was the calculation of conversion coefficients for absorbed doses per fluence (DT/Φ) using the sitting and standing male hybrid phantom (UFH/NCI) exposure to monoenergetic protons with energy ranging from 2 MeV to 10 GeV. Sex-averaged effective dose per fluence (E/Φ) using the results of DT/Φ for the male and female hybrid phantom in standing and sitting postures were also calculated. Results of E/Φ of UFH/NCI standing phantom were also compared with tabulated effective dose conversion coefficients provided in ICRP publication 116. To develop an exposure scenario implementing the male UFH/NCI phantom in sitting and standing postures was used the radiation transport code MCNPX. Whole-body irradiations were performed using the recommended irradiation geometries by ICRP publication 116 antero-posterior (AP), postero-anterior (PA), right and left lateral, rotational (ROT) and isotropic (ISO). In most organs, the conversion coefficients DT/Φ were similar for both postures. However, relative differences were significant for organs located in the lower abdominal region, such as prostate, testes and urinary bladder, especially in the AP geometry. Results of effective dose conversion coefficients were 18% higher in the standing posture of the UFH/NCI phantom, especially below 100 MeV in AP and PA. In lateral geometry, the conversion coefficients values below 20 MeV were 16% higher in the sitting posture. In ROT geometry, the differences were below 10%, for almost all energies. In ISO geometry, the differences in E/Φ were negligible. The results of E/Φ of UFH/NCI phantom were in general below the results of the conversion coefficients provided in ICRP publication 116.

Influence of beam incidence and irradiation parameters on stray neutron doses to healthy organs of pediatric patients treated for an intracranial tumor with passive scattering proton therapy.

PURPOSE: In scattering proton therapy, the beam incidence, i.e. the patient's orientation with respect to the beam axis, can significantly influence stray neutron doses although it is almost not documented in the literature. METHODS: MCNPX calculations were carried out to estimate stray neutron doses to 25 healthy organs of a 10-year-old female phantom treated for an intracranial tumor. Two beam incidences were considered in this article, namely a superior (SUP) field and a right lateral (RLAT) field. For both fields, a parametric study was performed varying proton beam energy, modulation width, collimator aperture and thickness, compensator thickness and air gap size. RESULTS: Using a standard beam line configuration for a craniopharyngioma treatment, neutron absorbed doses per therapeutic dose of 63µGyGy(-1) and 149µGyGy(-1) were found at the heart for the SUP and the RLAT fields, respectively. This dose discrepancy was explained by the different patient's orientations leading to changes in the distance between organs and the final collimator where external neutrons are mainly produced. Moreover, investigations on neutron spectral fluence at the heart showed that the number of neutrons was 2.5times higher for the RLAT field compared against the SUP field. Finally, the influence of some irradiation parameters on neutron doses was found to be different according to the beam incidence. CONCLUSION: Beam incidence was thus found to induce large variations in stray neutron doses, proving that this parameter could be optimized to enhance the radiation protection of the patient.

ICRP dose coefficients: computational development and current status.

Major current efforts within Committee 2 of the International Commission on Radiological Protection (ICRP) involve the development of dose coefficients for inhalation and ingestion of radionuclides, and those for exposure to environmental radiation fields. These efforts build upon changes in radiation and tissue weighting factors (Publication 103), radionuclide decay schemes (Publication 107), computational phantoms of the adult reference male and female (Publication 110), external dose coefficients for adult reference workers for idealised radiation fields (Publication 116), models of radionuclide intake (Publications 66, 100 and 130), and models of radionuclide systemic biokinetics (Publication 130). This paper will review the overall computational framework for both internal and external dose coefficients. For internal exposures, the work entails assessment of organ self-dose and cross-dose from monoenergetic particle emissions (specific absorbed fraction), absorbed dose per nuclear transformation (S value), time-integrated activity of the radionuclide in source tissues (inhalation, ingestion, and systemic biokinetic models), and their numerical combination to yield the organ equivalent dose or effective dose per activity inhaled or ingested. Various challenges are reviewed that were not included in the development of Publication 30 dose coefficients, which were based upon much more simplified biokinetic models and computational phantoms. For external exposures, the computations entail the characterisation of environmental radionuclide distributions, the transport of radiation particles through that environment, and the tracking of energy deposition to the organs of the exposed individual. Progress towards the development of dose coefficients to members of the general public (adolescents, children, infants and fetuses) are also reviewed.

The reference phantoms: voxel vs polygon.

The International Commission on Radiological Protection (ICRP) reference male and female adult phantoms, described in Publication 110, are voxel phantoms based on whole-body computed tomography scans of a male and a female patient, respectively. The voxel in-plane resolution and the slice thickness, of the order of a few millimetres, are insufficient for proper segmentation of smaller tissues such as the lens of the eye, the skin, and the walls of some organs. The calculated doses for these tissues therefore present some limitations, particularly for weakly penetrating radiation. Similarly, the Publication 110 phantoms cannot represent 8-40-µm-thick target regions in respiratory or alimentary tract organs. Separate stylised models have been used to represent these tissues for calculation of the ICRP reference dose coefficients (DCs). ICRP Committee 2 recently initiated a research project, the ultimate goal of which is to convert the Publication 110 phantoms to a high-quality polygon-mesh (PM) format, including all source and target regions, even those of the 8-40-µm-thick alimentary and respiratory tract organs. It is expected that the converted phantoms would lead to the same or very similar DCs as the Publication 110 reference phantoms for penetrating radiation and, at the same time, provide more accurate DCs for weakly penetrating radiation and small tissues. Additionally, the reference phantoms in the PM format would be easily deformable and, as such, could serve as a starting point to create phantoms of various postures for use, for example, in accidental dose calculations. This paper will discuss the current progress of the phantom conversion project and its significance for ICRP DC calculations.

ICRP Publication 133: The ICRP computational framework for internal dose assessment for reference adults: specific absorbed fractions.

Abstract ­: Dose coefficients for assessment of internal exposures to radionuclides are radiological protection quantities giving either the organ equivalent dose or effective dose per intake of radionuclide following ingestion or inhalation. In the International Commission on Radiological Protection's (ICRP) Occupational Intakes of Radionuclides (OIR) publication series, new biokinetic models for distribution of internalised radionuclides in the human body are presented as needed for establishing time-integrated activity within organs of deposition (source regions). This series of publications replaces Publications 30 and 68 (ICRP, 1979, 1980, 1981, 1988, 1994b). In addition, other fundamental data needed for computation of the dose coefficients are radionuclide decay data (energies and yields of emitted radiations), which are given in Publication 107 (ICRP, 2008), and specific absorbed fraction (SAF) values ­ defined as the fraction of the particle energy emitted in a source tissue region that is deposited in a target tissue region per mass of target tissue. This publication provides the technical basis for SAFs relevant to internalised radionuclide activity in the organs of Reference Adult Male and Reference Adult Female as defined in Publications 89 and 110 (ICRP, 2002, 2009). SAFs are given for uniform distributions of mono-energetic photons, electrons, alpha particles, and fission-spectrum neutrons over a range of relevant energies. Electron SAFs include both collision and radiative components of energy deposition. SAF data are matched to source and target organs of the biokinetic models of the OIR publication series, as well as the Publication 100 (ICRP, 2006) Human Alimentary Tract Model and the Publication 66 (ICRP, 1994a) Human Respiratory Tract Model, the latter as revised within Publication 130 (ICRP, 2015). This publication further outlines the computational methodology and nomenclature for assessment of internal dose in a manner consistent with that used for nuclear medicine applications. Numerical data for particle-specific and energy-dependent SAFs are given in electronic format for numerical coupling to the respiratory tract, alimentary tract, and systemic biokinetic models of the OIR publication series.

ICRP Publication 134: Occupational Intakes of Radionuclides: Part 2.

Abstract ­: The 2007 Recommendations of the International Commission on Radiological Protection (ICRP, 2007) introduced changes that affect the calculation of effective dose, and implied a revision of the dose coefficients for internal exposure, published previously in the Publication 30 series (ICRP, 1979, 1980, 1981, 1988b) and Publication 68 (ICRP, 1994b). In addition, new data are available that support an update of the radionuclide-specific information given in Publications 54 and 78 (ICRP, 1988a, 1997b) for the design of monitoring programmes and retrospective assessment of occupational internal doses. Provision of new biokinetic models, dose coefficients, monitoring methods, and bioassay data was performed by Committee 2, Task Group 21 on Internal Dosimetry, and Task Group 4 on Dose Calculations. A new series, the Occupational Intakes of Radionuclides (OIR) series, will replace the Publication 30 series and Publications 54, 68, and 78. Part 1 of the OIR series has been issued (ICRP, 2015), and describes the assessment of internal occupational exposure to radionuclides, biokinetic and dosimetric models, methods of individual and workplace monitoring, and general aspects of retrospective dose assessment. The following publications in the OIR series (Parts 2­5) will provide data on individual elements and their radioisotopes, including information on chemical forms encountered in the workplace; a list of principal radioisotopes and their physical half-lives and decay modes; the parameter values of the reference biokinetic model; and data on monitoring techniques for the radioisotopes encountered most commonly in workplaces. Reviews of data on inhalation, ingestion, and systemic biokinetics are also provided for most of the elements. Dosimetric data provided in the printed publications of the OIR series include tables of committed effective dose per intake (Sv per Bq intake) for inhalation and ingestion, tables of committed effective dose per content (Sv per Bq measurement) for inhalation, and graphs of retention and excretion data per Bq intake for inhalation. These data are provided for all absorption types and for the most common isotope(s) of each element. The electronic annex that accompanies the OIR series of reports contains a comprehensive set of committed effective and equivalent dose coefficients, committed effective dose per content functions, and reference bioassay functions. Data are provided for inhalation, ingestion, and direct input to blood. The present publication provides the above data for the following elements: hydrogen (H), carbon (C), phosphorus (P), sulphur (S), calcium (Ca), iron (Fe), cobalt (Co), zinc (Zn), strontium (Sr), yttrium (Y), zirconium (Zr), niobium (Nb), molybdenum (Mo), and technetium (Tc).

Dosimetric models of the eye and lens of the eye and their use in assessing dose coefficients for ocular exposures.

Based upon recent epidemiological studies of ocular exposure, the Main Commission of the International Commission on Radiological Protection (ICRP) in ICRP Publication 118 states that the threshold dose for radiation-induced cataracts is now considered to be approximately 0.5 Gy for both acute and fractionated exposures. Consequently, a reduction was also recommended for the occupational annual equivalent dose to the lens of the eye from 150 mSv to 20 mSv, averaged over defined periods of 5 years. To support ocular dose assessment and optimisation, Committee 2 included Annex F within ICRP Publication 116 . Annex F provides dose coefficients - absorbed dose per particle fluence - for photon, electron, and neutron irradiation of the eye and lens of the eye using two dosimetric models. The first approach uses the reference adult male and female voxel phantoms of ICRP Publication 110. The second approach uses the stylised eye model of Behrens et al., which itself is based on ocular dimensional data given in Charles and Brown. This article will review the data and models of Annex F with particular emphasis on how these models treat tissue regions thought to be associated with stem cells at risk.

Secondary neutron doses received by paediatric patients during intracranial proton therapy treatments.

This paper's goal is to assess secondary neutron doses received by paediatric patients treated for intracranial tumours using a 178 MeV proton beam. The MCNPX Monte Carlo model of the proton therapy facility, previously validated through experimental measurements for both proton and neutron dosimetry, was used. First, absorbed dose was calculated for organs located outside the clinical target volume using a series of hybrid computational phantoms for different ages and considering a realistic treatment plan. In general, secondary neutron dose was found to decrease as the distance to the treatment field increases and as the patient age increases. In addition, secondary neutron doses were studied as a function of the beam incidence. Next, neutron equivalent dose was assessed using organ-specific energy-dependent radiation weighting factors determined from Monte Carlo simulations of neutron spectra at each organ. The equivalent dose was found to reach a maximum value of ∼155 mSv at the level of the breasts for a delivery of 49 proton Gy to an intracranial tumour of a one-year-old female patient. Finally, a thorough comparison of the calculation results with published data demonstrated the dependence of neutron dose on the treatment configuration and proved the need for facility-specific and treatment-dependent neutron dose calculations.

Secondary neutron doses in proton therapy treatments of ocular melanoma and craniopharyngioma.

Monte Carlo simulations were used to assess secondary neutron doses received by patients treated with proton therapy for ocular melanoma and craniopharyngioma. MCNPX calculations of out-of-field doses were done for ∼20 different organs considering realistic treatment plans and using computational phantoms representative of an adult male individual. Simulations showed higher secondary neutron doses for intracranial treatments, ∼14 mGy to the salivary glands, when compared with ocular treatments, ∼0.6 mGy to the non-treated eye. This secondary dose increase is mainly due to the higher proton beam energy (178 vs. 75 MeV) as well as to the impact of the different beam parameters (modulation, collimation, field size etc.). Moreover, when compared with published data, the assessed secondary neutron doses showed similar trends, but sometimes with sensitive differences. This confirms secondary neutrons to be directly dependent on beam energy, modulation technique, treatment configuration and methodology.

Investigation of effect of variations in bone fraction and red marrow cellularity on bone marrow dosimetry in radio-immunotherapy.

A method is described for computing patient-specific absorbed dose rates to active marrow which accounts for spatial variation in bone volume fraction and marrow cellularity. A module has been added to the 3D Monte Carlo dosimetry program DPM to treat energy deposition in the components of bone spongiosa distinctly. Homogeneous voxels in regions containing bone spongiosa (as defined on CT images) are assumed to be comprised only of bone, active (red) marrow and inactive (yellow) marrow. Cellularities are determined from biopsy, and bone volume fractions are computed from cellularities and CT-derived voxel densities. Electrons are assumed to deposit energy locally in the three constituent components in proportions determined by electron energy absorption fractions which depend on energy, cellularity, and bone volume fraction, and which are either taken from the literature or are derived from Monte Carlo simulations using EGS5. Separate algorithms are used to model primary ß particles and secondary electrons generated after photon interactions. Treating energy deposition distinctly in bone spongiosa constituents leads to marrow dosimetry results which differ from homogeneous spongiosa dosimetry by up to 20%. Dose rates in active marrow regions with cellularities of 20, 50, and 80% can vary by up to 20%, and can differ by up to 10% as a function of bone volume fraction. Dose to bone marrow exhibits a strong dependence on marrow cellularity and a potentially significant dependence on bone volume fraction.

An image-based skeletal model for the ICRP reference adult male-specific absorbed fractions for neutron-generated recoil protons.

Recoiling hydrogen nuclei are a principle mechanism for energy deposition from incident neutrons. For neutrons incident on the human skeleton, the small sizes of two contrasting media (trabecular bone and marrow) present unique problems due to a lack of charged-particle (protons) equilibrium. Specific absorbed fractions have been computed for protons originating in the human skeletal tissues for use in computing neutron dose response functions. The proton specific absorbed fractions were computed using a pathlength-based range-energy calculation in trabecular skeletal samples of a 40 year old male cadaver.

Methods for the inclusion of shallow marrow and adipose tissue in pathlength-based skeletal dosimetry.

Distributions of linear pathlength measurements have been utilized in skeletal dosimetry of internally emitted short-range particles for over 30 years. This work reviews the methods for coupling these distributions to range-energy data. A revised methodology is presented for handling the insertion of the additional dosimetric target region (shallow marrow) and medium (adipose tissue) into the dosimetry algorithm. The methodology is shown to reduce the volume fraction of shallow marrow in the trabecular skeleton over existing methodologies. Finally, theoretical low and high-energy checkpoints are derived for use in checking the absorbed fraction and specific absorbed fraction results for a variety of source and target combinations.

New developments in internal dosimetry models.

This paper describes new biokinetic and dosimetric models, especially those being developed by ICRP which will be used in the forthcoming documents on Occupational Intakes of Radionuclides. It also presents the results of a working group within the European project CONRAD which is being continued within EURADOS. This group is implementing the new models, performing quality assurance of the model implementation (including their description) and giving guidance to the scientific community on the application of the models for individual dose assessment.

Impact on 141Ce, 144Ce, 95Zr, and 90Sr beta emitter dose coefficients of photon and electron SAFs calculated with ICRP/ICRU reference adult voxel computational phantoms.

The current dose coefficients for internal dose assessment of occupationally exposed persons and the general public were derived using the methodology of the International Commission on Radiological Protection (ICRP), which is similar to the Medical Internal Radiation Dose (MIRD)-type methodology. One component of this methodology is the mathematical representation of the human body (so-called MIRD-type phantoms) developed at the Oak Ridge National Laboratory for calculations of photon specific absorbed fractions (SAFs). Concerning the beta emissions, it is assumed in general that they irradiate only the organ where the radionuclide resides, whereas for walled organs, a fixed fraction of the emitted energy is absorbed within the wall. For the active marrow and bone surface targets, absorbed fractions were explicitly provided in ICRP Publication 30. The ICRP Publications 66 and 100 contain further detailed energy-dependent absorbed fraction data for the airways and the segments of the alimentary tract. In the present work, the voxel phantoms representing the reference male and female adults, recently developed at the Helmholtz Zentrum München-German Research Center for Environmental Health (HMGU) in collaboration with the Task Group DOCAL of ICRP Committee 2, were used for the Monte Carlo computation of photon as well as electron SAFs. These voxel phantoms, being constructed from computed tomography (CT) scans of individuals, are more realistic in shape and location of organs in the body than the mathematical phantoms; therefore, they provide photon SAFs that are more precise than those stemming from mathematical phantoms. In addition, electron SAFs for solid and walled organs as well as tissues in the alimentary tract, the respiratory tract, and the skeleton were calculated with Monte Carlo methods using these phantoms to complement the data of ICRP Publications 66 and 100 that are confined to self-irradiation. The SAFs derived for photons and electrons are then used to calculate the dose coefficients of the beta emitters 141Ce, 144Ce, 95Zr, and 90Sr. It is found that the differences of the dose coefficients due to the revised SAFs are much larger for injection and ingestion than for inhalation. The equivalent doses for colon and ingestion with the new voxel-based SAFs are significantly smaller than the values with the MIRD-type photon SAFs and simplifying assumptions for electrons. For lungs and inhalation, no significant difference was observed for the equivalent doses, whereas for injection and ingestion, an increase of the new values is observed.