Dose Related Literature

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Characterizing dose-related literature is not easy. There is a lot of great information out there, published by standing committees, appearing each month in a number of journals, published by national laboratories and other similar groups, and so on. We decided to summarize some of the major works by the large standing committees, to give some guidance on the most important documents that have been established in a consensus format. We also summarize some important recent literature in the areas of bone marrow dosimetry and relating dose to effect for nuclear medicine studies, which have been the focus of much recent work. Any suggestions you may have for other areas that could be covered are welcome. Generally speaking, you ask for it, you get it from RADAR!

RADAR Literature
MIRD Literature
ICRP Literature
NCRP Literature
IAEA Literature

Bone and marrow dose models
Relating dose to effect for internal emitters

RADAR Literature

RADAR is not an officially sanctioned committee, like MIRD, ICRP, and NCRP, but its members have published a number of documents, data sets, and tools with a literature basis that are clearly important to the current practice of dosimetry. We summarize some of the pertinent references here.

Selected RADAR member articles

Title	Authors	Publication Information	Comments
Specific absorbed fractions of energy at various ages from internal photons sources.	Cristy, M. and Eckerman, K	ORNL/TM-8381 V1-V7, 1987	Absorbed fractions for a pediatric phantom series
Mathematical Models and Specific Absorbed Fractions of Photon Energy in the Nonpregnant Adult Female and at the End of Each Trimester of Pregnancy	Stabin M, Watson E, Cristy M, Ryman J, Eckerman K, Davis J, Marshall D and Gehlen K.	ORNL Report ORNL/TM 12907, 1995	Absorbed fractions for the pregnant female
MIRDOSE: Personal Computer Software for Internal Dose Assessment in Nuclear Medicine	Stabin M	J Nucl Med 37(3):538-546, 1996	Description of the MIRDOSE software
Radiation Dose Estimates for Radiopharmaceuticals	Stabin MG, Stubbs JB and Toohey RE	NUREG/CR-6345, 1996	Dose estimates for adults for a number of radiopharmaceuticals
Radiation Absorbed Dose to the Embryo/Fetus from Radiopharmaceuticals	Russell JR and Stabin MG, Sparks RB and Watson EE	Health Phys 73(5):756-769, 1997	The title says it all.
Electron absorbed fractions and dose conversion factors for marrow and bone by skeletal regions	Eckerman K and Stabin M	Health Phys. 78(2):199-214, 2000	Bone/marrow dose model for children and adults
Re-evaluation of Absorbed Fractions for Photons and Electrons in Small Spheres	Stabin MG and Konijnenberg M	J Nucl Med 41:149-160, 2000	New sphere absorbed fractions
New Decay Data For Internal and External Dose Assessment	Stabin MG and da Luz CQPL	Health Phys. 83(4):471-475, 2002	Decay data for >800 radionuclides, used to develop RADAR dose factors
Physical Models and Dose Factors For Use In Internal Dose Assessment	Stabin MG and Siegel JA	Health Phys. 2003, galleys approved	Dose factors for >800 radionuclides and 15 phantoms

MIRD Literature - The MIRD Pamphlets

A MIRD Pamphlet is a document which generally contains material needed to implement the MIRD schema for internal dose calculations, including equations, data, methods, etc. Several of the MIRD Pamphlets were issued and then revised and reissued; therefore, some of the MIRD Pamphlet titles contain the word 'revised'. Most of the important MIRD Pamphlets are shown below. MIRD 1, revised has been superceded by the MIRD Primer (see books, below). MIRD 5 and 5, revised are not much in use, as the Cristy-Eckerman phantom series is widely used. MIRD Pamphlets 3 and 8 are also not much in use, as new absorbed fractions for spheres were calculated (Stabin and Konijnenberg, J Nucl Med 41:149-160, 2000), and problems with the MIRD values were pointed out.

Selected MIRD Pamphlets

Pamphlet	Publication Date	Main Information	Comments
1, 1 revised	1968, 1976	Discussion of MIRD internal dose technique	Superceded by the MIRD Primer (1988)
3	1968	Photon absorbed fractions for small objects	Superceded by J Nucl Med 41:149-160, 2000
5, 5 revised	1969, 1978	Description of anthropomorphic phantom representing Reference Man, photon absorbed fractions for many organs	Superceded by availability of Cristy/Eckerman phantom series (1987)
7	1971	Dose distribution around point sources, electron, beta emitters	Good data, difficult to use; use of Monte Carlo codes like MCNP, EGS is generally preferred
8	1971	Photon absorbed fractions for small objects	Same as Pamphlet 3, smaller objects, also superceded by J Nucl Med 41:149-160, 2000
11	1975	S-values for many nuclides	Newer S values available, see RADAR dose factor page
12	1977	Discussion of kinetic models for internal dosimetry
13	1981	Description of model of the heart, photon absorbed fractions
14, 14 revised	1992, 1999	Dynamic urinary bladder for absorbed dose calculations	Software soon available, see RADAR software page
15	1996	Description of model for the brain, photon absorbed fractions
16	1999	Outline of best practices and methods for collecting and analyzing kinetic data	Widely cited, useful document
17	1999	S values for voxel sources
18	2001	Administered activity for xenon studies
19	2003	Multipart kidney model with absorbed fractions

MIRD Literature - The MIRD Dose Estimate Reports

The MIRD Dose Estimate Reports contain radiation dosimetry for particular radiopharmaceuticals, along with the kinetic model employed. They were published as separate articles in the Journal of Nuclear Medicine (as are the reports after number 12) and are mostly quite similar. The first table in the article is usually a summary of the dose estimates for all significant organs for unit administrations of the pharmaceutical. Later tables and figures show some of the developmental material used to calculate the dose estimates. All of these estimates contain some useful information, except perhaps in cases in which the pharmaceutical is no longer in use. The kinetic models are presented in various ways which must be studied individually.

Selected MIRD Dose Estimate Reports

Dose Estimate Report Number	Publication Reference	Compound or Pharmaceutical Studied
1	J Nucl Med 14:49-50,1973	Se-75-L-Selenomethionine
2	J Nucl Med 14:755-756,1973	Ga-66-, Ga-67-, Ga-68-, and Ga-72-Citrate
3	J Nucl Med 16:108A-108B,1975	Tc-99m-Sulfur Colloid in Various Liver Conditions
4	J Nucl Med 16:173-174, 1975	Au-198-Colloidal Gold in Various Liver Conditions
5	J Nucl Med 16:857-860,1975	I-123, I-124, I-125, I-126,I-130,I-131, and I-132 as Sodium Iodide
6	J Nucl Med 16:1095-1098,1975	Hg-197- and Hg-203-Labeled Chlormerodrin
7	J Nucl Med 16:1214-1217,1975	I-123, I-124, I-126, I-130, and I-131 as Sodium Rose Bengal
8	J Nucl Med 17:74-77,1976	Tc-99m as Sodium Pertechnetate
9	J Nucl Med 21:459-465, 1980	Radioxenons in Lung Imaging
10	J Nucl Med 23:915-917,1982	Albumin Microspheres Labeled with Tc-99m
11	J Nucl Med 24:339-348,1983	Fe-52, Fe-55, and Fe-59 Used to Study Ferrokinetics
12	J Nucl Med 25:503-505,1984	Tc-99m Diethylenetriaminepentaacetic Acid
13	J Nucl Med 30:1117-1122, 1989	Tc-99m Labeled Bone Imaging Agents
14	J Nucl Med 31:378-380, 1990	Tc-99m Labeled Red Blood Cells
15	J Nucl Med 33:777-780, 1992	Radioindium-Lableled Autologous Platelets
16	J Nucl Med 33:1717-1719, 1992	Tc-99m Diethylenetriaminepentaacetic Acid Aerosol
17	J Nucl Med 34:1382-1384, 1993	Inhaled Kr-81m Gas in Lung Imaging
18	J Nucl Med 39:671-676, 1998	Indium 111 B72.3 (IgG Antibody to Ovarian and Colorectal Caner)

The MIRD Literature - MIRD Books

The MIRD Committee has published a number of books as well, which are not exactly pamphlets:

The MIRD Primer (Loevinger et al. 1988), described above.
A set of decay data was published in 1988 (Weber et al. 1989), which replaced old MIRD compendia of decay data (MIRD pamphlets 4, 6, and 10). These data are, however, also now somewhat dated.
In 1998, a tabulation of S values was published for cellular sources and targets activity being on the surface of a cell (of various dimensions), in the cytoplasm, or uniformly throughout the entire cell, with the target being the whole cell or the nucleus.

The ICRP Literature

Selected ICRP Reports

Interested readers can visit the ICRP Report Abstract Page for more detail and ordering information regarding these reports.

Report No	Publication Date	Main Information	Comments
23	1975	Reference Man: Anatomical, Physiological and Metabolic Characteristics	Cornerstone document for many years, with anatomical data needed for standard dose values. Now superceded by ICRP 89 (2003)
30	1979	Limits for the Intake of Radionuclides by Workers, Part 1	Dosimetric models, dose factors, tons of data in the report and supplements. Basis for current US regulations.
34	1983	Protection of the Patient in Diagnostic Radiology	Guidance for radiologists in managing patient dose. Supercedes Report 16.
41	1984	Nonstochastic Effects of Ionizing Radiation	Overview of, well, what the title says!
44	1985	Protection of the Patient in Radiation Therapy, 44	Companion to Report 34.
52	1988	Protection of the Patient in Nuclear Medicine	Widely used and cited document - guidelines for good practice in nuclear medicine. Guidance for pregnant women has been superceded in Report 90.
53, 80	1988	Radiation Dose to Patients from Radiopharmaceuticals	Landmark documents, establishing dosimetry for many radionuclides. Supplemented in other reports with minor appendices. Soon to be organized together on a searchable CD.
54	1989	Individual Monitoring for Intakes of Radionuclides by Workers: Design and Interpretation	Models and IRFs for many compounds. Criticized in some cases for having unrealistic models. Still a good reference, but superceded by more recent treatments (e.g. Health Phys 83(5), ICRP 78).
56, 67, 68, 69, 71, 72	1990-1996	Series of reports on age-dependent dose factors for inhalation and ingestion.	Invaluable resource. Some dose factors also published by the IAEA and available on the RADAR Occupational Dose Factors Page
59	1992	The Biological Basis for Dose Limitation in the Skin	Nice reference on this important subject.
60	1991	1990 Recommendations of the International Commission on Radiological Protection	Landmark document, an update on, and meant to supercede ICRP 30. All countries except the USA have adopted the dose limits and methods proposed here. The US took one year to implement ICRP II, 15 years to implement ICRP 30, still counting time on this one.
66	1995	Human Respiratory Tract Model for Radiological Protection	Detailed (and I mean detailed) description of the new lung model, applied in ICRP 60 recommendations.
70, 89	1996 and 2003	New anatomical reference data.	70 treats the skeleton only, 89 covers all else. Supercedes ICRP 23.
74	1997	Conversion Coefficients for use in Radiological Protection against External Radiation
78	1999	Individual Monitoring for Internal Exposure of Workers	Supercedes ICRP 54.
84	2001	Pregnancy and Medical Radiation	Very nice overview of the subject, recommendations for interpretation of medical exposures and advice to patient.
87	2002	Managing Patient Dose in Computed Tomography
88	2002	Doses to the Embryo and Fetus from Intakes of Radionuclides by the Mother	Another landmark document, giving embryo and fetal doses for pregnant workers exposed occupationally. All of the models are not that strong, but, like with radiopharmaceuticals, these are the best doses based on the available information.
90	2004	Biological Effects after Prenatal Irradiation (Embryo and Fetus)
92	2004	Relative Biological Effectiveness (RBE), Quality Factor (Q), and Radiation Weighting Factor (wR)	2004 update on our knowledge of biological effects.
93	2004	Managing Patient Dose in Digital Radiology

The NCRP Literature

Selected NCRP Reports

Some of these go back pretty far in time, but are important for historical reasons, and some are still used. Interested readers can visit the NCRP Reports Page for more detail and ordering information regarding these reports.

Report	Publication Date	Main Information	Comments
37	1970	Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides	Good, practical guide, included guidance on handling radioactive cadavers.
49	1976	Structural Shielding Design and Evaluation for Medical Use of X Rays and Gamma Rays of Energies up to 10 MeV	Pretty much the Bible on X-ray shielding for lo these many years. A replacement is very soon to be published, but this is still the best work on this subject.
54	1977	Medical Radiation Exposure of Pregnant and Potentially Pregnant Women	Very widely cited for many years, now superceded by the ICRP documents noted above.
65	1980	Management of Persons Accidentally Contaminated with Radionuclides	Another Bible on this topic. Widely used and cited. Current homeland security interests have sparked interest in an update. A committee is meeting now, new version hopefully by the end of 2005.
70	1982	Nuclear Medicine—Factors Influencing the Choice and Use of Radionuclides in Diagnosis and Therapy	Very nice document, but somewhat out of date. The principles still apply.
76	1984	Radiological Assessment: Predicting the Transport, Bioaccumulation, and Uptake by Man of Radionuclides Released to the Environment	Another very good summary, somewhat dated.
78	1984	Evaluation of Occupational and Environmental Exposures to Radon and Radon Daughters in the United States	Important summary document.
83, 84	1985	The Experimental Basis for Absorbed-Dose Calculations in Medical Uses of Radionuclides, and General Concepts for the Dosimetry of Internally Deposited Radionuclides	Interesting theoretical documents, but they have not found much practical application.
87	1987	Use of Bioassay Procedures for Assessment of Internal Radionuclide Deposition	Very short document that supplements some of the more practical ICRP documents noted above.
105	1989	Radiation Protection for Medical and Allied Health Personnel	Supercedes Report 48.
106	1989	Limit for Exposure to "Hot Particles" on the Skin	Treatment of a unique topic.
125	1997	Deposition, Retention and Dosimetry of Inhaled Radioactive Substances	Good anatomic and physiologic treatment. Complements treatment in ICRP 66 model description.
128	1998	Radionuclide Exposure of the Embryo/Fetus	Extensive anatomic/physiologic data on fetal development and placental crossover, knowledge base for a large number of elements.
136	2001	Evaluation of the Linear-Nonthreshold Dose-Response Model for Ionizing Radiation	Wading into the deep waters of the LNT debate. Bottom line: "no conclusive evidence on which to reject the assumption of a linear-nonthreshold dose-response relationship..." Lots of biological and epidemiological data, brief treatment of hormesis.
138	2001	Management of Terrorist Events Involving Radioactive Material	Excellent treatment of this pertinent and interesting subject.
146	2004	Approaches to Risk Management in Remediation of Radioactively Contaminated Sites	Overview of regulatory approaches of NRC and EPA, summary of risk models, decision making strategies, case studies. Important reading.

The IAEA Literature

It is hard to imagine the area of radiation protection without the International Atomic Energy Agency (IAEA). Although the United States has the human and financial resources to establish its own regulatory and normative infrastructure, most of the rest of the world depends on the IAEA for its work in standardization, organization of international work groups, information infrastructure, emergency assistance and radioactive waste and safeguards activities.

The history of the IAEA is given in the document The history of the IAEA. Eighty-one nations approved the IAEA statute in 1956. Eisenhower, as one of the creators of the Agency, wanted it to serve as the stockpile of fissile material for all the nations in the world. The IAEA would take the material “out of the hand of soldiers” and to give it to those who would “adapt it to the arts of peace”. The original purpose of the IAEA was not fulfilled, but the IAEA efforts to promote the safe use of radiation and radionuclides in the interest of “the arts of peace” have gone further than any of the founders could have imagined.

The IAEA is now almost constantly “in the press”. From Depleted Uranium to Iraq arms inspections to North Korea. The IAEA tries to solve technical problems which have become political questions. The mixture of technical competency with a policy of “transparency” has gone a long way to assure the IAEA acceptance in almost all of the countries of the world. IAEA publications The IAEA maintains an up-to-date list of its publications at this site. The publications are divided into:

The Safety Guide Series; The Safety Series (the “International Basic Safety Standards for Protection Against Ionizing Radiation and for the Safety of Radiation Sources: A Safety Standard” of 1996 is perhaps the most important);
The Safety Reports series;
The Technical Reports Series;
The IAEA Technical Documents;
The Accident Response Reports.

A list of recently released publications is also available. The IAEA normally does not open to the “general public” the possibility of revising a document before publication. The IAEA sends a draft document to the “National Authority” of the member country for distribution for comments. IAEA databases The IAEA databases are excellent sources of information, even nowadays with the facilities provided through the internet. The main database is the International Nuclear Information System (INIS) The Future of the IAEA The IAEA, in common with many other organizations, is suffering from financial restrictions. One of its main aims continues to be to control nuclear proliferation, and this is seen to be an “almost impossible” task using peaceful methods. As the worries of nuclear terrorism and the use of radioactive materials as weapons of mass destruction are increasing daily, the IAEA will certainly be “in the news” for many years to come.

Bone and Marrow Dose Models

The absorbed dose to the red marrow is one of the most important parameters of interest in internal dose assessment involving therapeutic applications, because of potential marrow toxicity. This quantity has been very difficult to estimate, however, because of the very complex geometry involved in the trabecular bone and the general difficulty in the evaluation of absorbed dose in this mixed medium problem. Spiers and coworkers provided much material in the literature, primarily dealing with the evaluation of absorbed dose to the marrow from electron and beta emitters in the volume of mineral bone (see various publications of Spiers, Beddoe and colleagues - full references in our on-line internal dose course). In their method, electrons originating in bone lost energy in that region of bone and subsequent regions of marrow or bone according to the continuous slowing down approximation (CSDA). Bone and marrow region dimensions were chosen stochastically from frequency distributions determined from measurements on samples of bone segments from humans. Thus, a Monte Carlo simulation method was employed that gave averages for energy deposition in marrow from sources in bone. Absorbed fractions for this case, as well as for other cases such as marrow irradiating marrow, were derived. This information was combined with the Monte Carlo simulations for photons in the Fisher-Snyder phantom to give the S values in MIRD Pamphlet No. 11, which have been used for many years. The absorbed fractions employed in MIRD 11 for bone irradiating marrow were known to be conservatively high for photons below about 300 keV, as stated by the authors themselves. The photon absorbed fractions of Cristy and Eckerman (see RADAR Literature section above) incorporated an improvement in the low energy photon dosimetry to correct for this problem. The improvement introduced by Cristy and Eckerman basically involved the modeling of energy deposition by secondary electrons liberated by photon interactions in the skeleton. The International Commission on Radiological Protection (ICRP), in ICRP Publication 30 (see ICRP Literature section above), made limited use of the data of Spiers and coworkers, and employed photon SAFs from ICRP Publication 23, in developing dosimetry for a number of radionuclides within the framework of a system of radiation protection for workers. More recently, Eckerman (see RADAR Literature section above) recalculated the values of Spiers and coworkers, in order to establish the absorbed fractions for electrons for most bone groups across a wide range of energies and to combine them with the newer photon specific absorbed fractions (SAFs). The seven bone types identified by Spiers et al. were combined with various assumed fractional abundances of each bone type (n = 7) within different bone regions (n = 15) of the Cristy/Eckerman phantom series. This model allows calculation of absorbed dose to the marrow by marrow region. The Eckerman model also makes possible the use of the fractions of marrow assigned to different bone regions to develop dose-volume histograms, which show what fractions of the marrow receive different absorbed doses, given the regional absorbed dose distribution calculated from the model.

A similar investigation by Bouchet et al. (J Nucl Med 40:62S-101S, 1999), working with the same input trabecular bone and marrow cavity chord length distributions, but employing a different transport algorithm, basically confirmed the accuracy of the Eckerman derived values. Bouchet et al. provide important information on the distributions of marrow in various bone sites based on the more recent ICRP 70 publication. Bouchet et al. did not, however, account for marrow cellularity in their calculation of red marrow self-dose S values. Both the Bouchet et al. and Eckerman models calculate the absorbed fraction for marrow space irradiating marrow space (not red marrow irradiating red marrow). As an electron passes across a marrow cavity, or many marrow cavities, the fraction of its energy deposited in the red marrow within that space will be proportional to the cellularity (the fraction of marrow that is active marrow). This was accounted for in the Eckerman model but not in the Bouchet et al. Model. Therefore, the Bouchet et al. computed S values for many nuclides is closer to the values from the ICRP 30 model (which is known to be overly conservative) than to those of MIRD 11 or from the Eckerman model. This omission of the cellularity from their calculations was intentional; they did not believe that it should be included, because as the electron energy goes to zero, the marrow-to-marrow absorbed fraction does not go to 1.0, but to the value of cellularity for that bone. It is true that this value should converge to 1.0 at very low energies; it is also true that in the Eckerman model this does not occur (i.e. the absorbed fractions converge to the cellularity at zero energy). At most energies, however, the cellularity must be included, and the S values from the Eckerman model (as provided by the MIRDOSE software) are more reliable. A "consensus bone model" was recently derived (Cancer Biotherapy and Radiopharmaceuticals, 17(4):427-434, 2002), which resolved the two models by allowing the absorbed fractions to be modified by the cellularity at most electron energies, but in which they also converge to 1.0 at zero energy. These AFs are used as the basis for the current RADAR and OLINDA/EXM bone and marrow S values.

Some other recent literature has been helpful on this subject as well. Three RADAR members wrote a paper entitled Sensitivity of Model-Based Calculations of Red Marrow Dosimetry to Changes in Patient-Specific Parameters (Cancer Biotherapy and Radiopharmaceuticals 17(5): 535-543, 2002). As the title implied, this paper studied the sensitivity of calculated marrow dose to changes in assumptions about marrow uptake (specific binding vs. use of the blood-based model to predict marrow activity), individual subject's marrow mass, the presence of free radionuclide (Y-90 or I-131) in radiopharmaceutical preparations, marrow cellularity, and other factors. Two other recent papers that showed some significant improvements in correlating marrow dose with observed toxicity included the paper on the use of FLT3-L stimulatory cytokine levels in blood to attempt to adjust for marrow sensitivity (Siegel et al., J. Nucl. Med 2003 44: 67-76), and a paper by Shen et al. using a patient-specific marrow dose calculation technique entitled Improved Prediction of Myelotoxicity Using a Patient-Specific Imaging Dose Estimate for Non-Marrow-Targeting 90Y-Antibody Therapy (J. Nucl. Med. 2002 43: 1245-1253).

Relating dose to effect for internal emitters

(under construction)