Keith F. Eckerman

MIRD Pamphlet No. 21: A Generalized Schema for Radiopharmaceutical Dosimetry—Standardization of Nomenclature

The internal dosimetry schema of the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine has provided a broad framework for assessment of the absorbed dose to whole organs, tissue subregions, voxelized tissue structures, and individual cellular compartments for use in both diagnostic and therapeutic nuclear medicine. The schema was originally published in 1968, revised in 1976, and republished in didactic form with comprehensive examples as the MIRD primer in 1988 and 1991. The International Commission on Radiological Protection (ICRP) is an organization that also supplies dosimetric models and technical data, for use in providing recommendations for limits on ionizing radiation exposure to workers and members of the general public. The ICRP has developed a dosimetry schema similar to that of the MIRD Committee but has used different terminology and symbols for fundamental quantities such as the absorbed fraction, specific absorbed fraction, and various dose coefficients. The MIRD Committee objectives for this pamphlet are 3-fold: to restate its schema for assessment of absorbed dose in a manner consistent with the needs of both the nuclear medicine and the radiation protection communities, with the goal of standardizing nomenclature; to formally adopt the dosimetry quantities equivalent dose and effective dose for use in comparative evaluations of potential risks of radiation-induced stochastic effects to patients after nuclear medicine procedures; and to discuss the need to identify dosimetry quantities based on absorbed dose that address deterministic effects relevant to targeted radionuclide therapy.

Mathematical models and specific absorbed fractions of photon energy in the nonpregnant adult female and at the end of each trimester of pregnancy

Mathematical phantoms representing the adult female at three, six, and nine months of gestation are described. They are modifications of the 15-year-old male/adult female phantom (15-AF phantom) of Cristy and Eckerman (1987). The model of uterine contents includes the fetus, fetal skeleton, and placenta. The model is suitable for dose calculations for the fetus as a whole; individual organs within the fetus (other than the skeleton) are not modeled. A new model for the nonpregnant adult female is also described, comprising (1) the 15-AF phantom; (2) an adjustment to specific absorbed fractions for organ self-dose from photons to better match Reference Woman masses; and (3) computation of specific absorbed fractions with Reference Woman masses from ICRP Publication 23 for both penetrating and nonpenetrating radiations. Specific absorbed fractions for photons emitted from various source regions are tabulated for the new non;pregnant adult female model and the three pregnancy models.

Electron absorbed fractions and dose conversion factors for marrow and bone by skeletal regions.

The possible inductions of bone cancer and leukemia are the two health effects of primary concern in the irradiation of the skeleton. The relevant target tissues to consider in the dosimetric evaluation have been the cells on or near endosteal surfaces of bone, from which osteosarcomas are thought to arise, and hematopoietic bone marrow, which is associated with leukemia. The complex geometry of the soft tissue-bone intermixture makes calculations of absorbed doses to these target regions a difficult problem. In the case of photon or neutron radiations, charged particle equilibrium may not exist in the vicinity of a soft tissue-bone mineral interface. In this paper, absorbed fraction data are developed for calculations of the dose in the target tissues from electron emitters deposited within the volume or on the surfaces of trabecular bone. The skeletal average absorbed fractions presented are consistent with usage of this quantity in the contemporary dosimetric formulations of the International Commission on Radiological Protection (ICRP). Implementation of the new bone and marrow model is then developed within the context of the calculational schema of the Medical Internal Radiation Dose (MIRD) Committee. Model parameters relevant to the calculation of dose conversion factors (S values) for different regions of the skeleton of individuals of various age are described, and an example calculation is performed for a monoclonal antibody which localizes in the marrow. The utility of these calculations for radiation dose calculations in nuclear medicine is discussed.

Mayak Worker Study: An Improved Biokinetic Model for Reconstructing Doses from Internally Deposited Plutonium

Abstract Leggett, R. W., Eckerman, K. F., Khokhryakov, V. F., Suslova, K. G., Krahenbuhl, M. P. and Miller, S. C. Mayak Worker Study: An Improved Biokinetic Model for Reconstructing Doses from Internally Deposited Plutonium. Radiat. Res. 164, 111–122 (2005). The plutonium production facility known as the Mayak Production Association was put into operation in June 1948. A high incidence of cancer in the Mayak workers has been related to the level of exposure to plutonium, but uncertainties in tissue doses have hampered development of dose–risk relationships. As part of an effort to improve dose estimates for these workers, the systemic biokinetic model for plutonium currently recommended by the International Commission on Radiological Protection (ICRP) has been modified to reflect recently developed data and facilitate interpretation of case-specific information. This paper describes the proposed model and discusses its implications for dose reconstruction for the Mayak workers.

Revisions to the ORNL series of adult and pediatric computational phantoms for use with the MIRD schema.

The age-dependent series of stylized computational phantoms developed at the Oak Ridge National Laboratory in the late 1970’s to early 1980’s has found wide applicability in dosimetry studies ranging from dose coefficient compilations for external and internal photon emitters, simulations of patient radiological exams, and dose reconstruction activities. In the present study, we report on a series of revisions to the Oak Ridge National Laboratory series for their intended use within the MIRD schema of medical internal dosimetry. These revisions were made to (1) incorporate recent developments in stylized models of the head, brain, kidneys, rectosigmoid colon, and extra-pulmonary airways; (2) incorporate new models of the salivary glands and the mucosa layer of the urinary bladder, alimentary tract organs, and respiratory airways; (3) adopt reference values of elemental tissue compositions and mass densities from ICRP Publication 89 and ICRU Report 46; (4) provide for explicit treatment of left and right organs within organ pairs; (5) provide for a systematic tabulation of electron absorbed fractions as a function of energy and subject age for all internal organs; and (6) provide for methods of deriving patient-specific values of the specific absorbed fraction for both electrons and photons through interpolation/extrapolation of their phantom-derived values. While tomographic computational phantoms provide improved anatomic realism given the CT or MR image sets used in their construction, there does not yet exist a comprehensive series of reference pediatric tomographic phantoms, nor the ability to simulate very fine anatomic structures as can be modeled via mathematical approximation. Consequently, stylized pediatric phantoms will continue to fill this data need in medical dosimetry.

Mayak worker dosimetry study : An overview

The Mayak Production Association (MPA) was the first plutonium production plant in the former Soviet Union. Workers at the MPA were exposed to relatively large internal radiation intakes and external radiation exposures, particularly in the early years of plant operations. This paper describes the updated dosimetry database, “Doses-2005.” Doses-2005 represents a significant improvement in the determination of absorbed organ dose from external radiation and plutonium intake for the original cohort of 18,831 Mayak workers. The methods of dose reconstruction of absorbed organ doses from external radiation uses: 1) archive records of measured dose and worker exposure history, 2) measured energy and directional response characteristics of historical Mayak film dosimeters, and 3) calculated dose conversion factors for Mayak Study-defined exposure scenarios using Monte Carlo techniques. The methods of dose reconstruction for plutonium intake uses two revised models developed from empirical data derived from bioassay and autopsy cases and/or updates from prevailing or emerging International Commission on Radiological Protection models. Other sources of potential significant exposure to workers such as medical diagnostic x-rays, ambient onsite external radiation, neutron radiation, intake of airborne effluent, and intake of nuclides other than plutonium were evaluated to determine their impact on the dose estimates.

Lung Cancer in Mayak Workers

Abstract Gilbert, E. S., Koshurnikova, N. A., Sokolnikov, M. E., Shilnikova, N. S., Preston, D. L., Ron, E., Okatenko, P. V., Khokhryakov, V. F., Vasilenko, E. K., Miller, S., Eckerman, K. and Romanov, S. A. Lung Cancer in Mayak Workers. Radiat. Res. 162, 505–516 (2004). The cohort of nuclear workers at the Mayak Production Association, located in the Russian Federation, is a unique resource for providing information on the health effects of exposure to plutonium as well as the effects of protracted external dose. Lung cancer mortality risks were evaluated in 21,790 Mayak workers, a much larger group than included in previous evaluations of lung cancer risks in this cohort. These analyses, which included 655 lung cancer deaths occurring in the period 1955–2000, were the first to evaluate both excess relative risk (ERR) and excess absolute risk (EAR) models and to give detailed attention to the modifying effects of gender, attained age and age at hire. Lung cancer risks were found to be significantly related to both internal dose to the lung from plutonium and external dose, and risks were described adequately by linear functions. For internal dose, the ERR per gray for females was about four times higher than that for males, whereas the EAR for females was less than half that for males; the ERR showed a strong decline with attained age, whereas the EAR increased with attained age until about age 65 and then decreased. Parallel analyses of lung cancer mortality risks in Mayak workers and Japanese A-bomb survivors were also conducted. Efforts currently under way to improve both internal and external dose estimates, and to develop data on smoking, should result in more accurate risk estimates in the future.

MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative 177Lu SPECT Applied for Dosimetry of Radiopharmaceutical Therapy

The accuracy of absorbed dose calculations in personalized internal radionuclide therapy is directly related to the accuracy of the activity (or activity concentration) estimates obtained at each of the imaging time points. MIRD Pamphlet no. 23 presented a general overview of methods that are required for quantitative SPECT imaging. The present document is next in a series of isotope-specific guidelines and recommendations that follow the general information that was provided in MIRD 23. This paper focuses on 177Lu (lutetium) and its application in radiopharmaceutical therapy.

Strontium-90 in bone: a case study in age-dependent dosimetric modeling.

There is an increasing need for age-dependent dosimetric models, and it would be desirable to develop these models in such a way that the uniformity and basic features of the standard man models are retained. Unfortunately, available data concerning the age-dependent retention of nuclides would rarely permit the identification of compartments, uptake fractions, and clearance times using the empirical fitting methods that characterize the development of many adult models. However, in cases where compartments can be made to correspond to physically identifiable processes or subsections within an organ, it may be possible to combine relatively extensive information concerning the development of the human body with generally sparse nuclide-specific information to construct age-dependent compartmental models. In some cases there may be sufficient data to identify trends with age within compartments using empirical fitting techniques, provided the compartments have already been identified on physical bases. To obtain models that describe changes in a continuous manner from birth through adulthood, it may be necessary in many cases to modify existing adult models to consider fewer (or more easily identifiable) compartments. In this article we describe an age-dependent model for retention of ingested 90Sr in bone that exemplifies these concepts.

Evolution and Status of Bone and Marrow Dose Models

Investigations at the University of Leeds under the direction of F.W. Spiers in the early 1960s through the late 1970s established the first comprehensive assessment of marrow dose conversion factors (DCFs) for beta-emitting radionuclides within the volume or on the surface of trabecular bone. These DCFs were subsequently used in deriving radionuclide S values for skeletal tissues published in MIRD Pamphlet No. 11. Eckerman re-evaluated this work and extended the methods of Spiers to radionuclides within the marrow to provide DCFs for fifteen skeletal regions in computational models representing individuals of six different ages. These results were used in the MIRDOSE3 software. Bouchet et al. used updated information on regional bone and marrow masses, as well as 3D electron transport techniques, to derive radionuclide S values in skeletal regions of the adult. Although these two efforts are similar in most regards, the models differ in three respects in: (1) the definition of the red marrow region, (2) the definition of a surface source of activity, and (3) the assumption applied in transporting electrons through the trabecular endosteum. In this study, a review of chord-based skeletal models is given, followed by a description of the differences in the Eckerman and Bouchet et al. transport models. Finally, new data from NMR microscopy and radiation transport in trabecular bone is applied to address item (1) above. Dose conversion factors from MIRD 11, the Eckerman model, the Bouchet et al. model, and a revised model are compared for several radionuclides important to internal emitter therapy.