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Abstract: The OLINDA/EXM version 2.0 personal computer code was created as an upgrade to the widely used OLINDA/EXM 1.0 and 1.1 codes. This paper documents the upgrades that were implemented. New decay data and anthropomorphic and biokinetic models were implemented in the software, and the software alpha and beta tested. Agreement of doses between the OLINDA/EXM codes 1 and 2 was very good. Use of the new anthropomorphic and biokinetic models results in understandable differences between the codes. Previous models were retained in the new code, and those results were identical to those in the previous code. OLINDA/EXM 2.0 represents an upgrade from version 1, with new modeling data recommended by the international community. It standardizes internal dose calculations for dose assessments in clinical trials with radiopharmaceuticals, theoretical calculations for existing pharmaceuticals, teaching, and other purposes., Competing Interests: The author receives royalties for distribution of the software; otherwise, there are no conflicts of interest., (Copyright © 2023 Health Physics Society.)

With the recent approval of 177 Lu-DOTATATE for use in gastroenteropancreatic neuroendocrine tumors, access to peptide receptor radionuclide therapy is increasing. Representatives from the North American Neuroendocrine Tumor Society and the Society of Nuclear Medicine and Molecular Imaging collaborated to develop a practical consensus guideline for the administration of 177 Lu-DOTATATE. In this paper, we discuss patient screening, maintenance somatostatin analog therapy requirements, treatment location and room preparation, drug administration, and patient release as well as strategies for radiation safety, toxicity monitoring, management of potential complications, and follow-up. Controversies regarding the role of radiation dosimetry are discussed as well. This document is designed to provide practical guidance on how to safely treat patients with this therapy., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Widely used release criteria for patients receiving radiopharmaceuticals (NUREG-1556, Vol. 9, Rev.1, Appendix U) are known to be overly conservative. The authors measured external exposure rates near patients treated with I, Tc, and F and compared the measurements to calculated values using point and line source models. The external exposure dose rates for 231, 11, and 52 patients scanned or treated with I, Tc, and F, respectively, were measured at 0.3 m and 1.0 m shortly after radiopharmaceutical administration. Calculated values were always higher than measured values and suggested the application of "self-shielding factors," as suggested by Siegel et al. in 2002. The self-shielding factors of point and line source models for I at 1 m were 0.60 ± 0.16 and 0.73 ± 0.20, respectively. For Tc patients, the self-shielding factors for point and line source models were 0.44 ± 0.19 and 0.55 ± 0.23, and the values were 0.50 ± 0.09 and 0.60 ± 0.12, respectively, for F (all FDG) patients. Treating patients as unshielded point sources of radiation is clearly inappropriate. In reality, they are volume sources, but treatment of their exposures using a line source model with appropriate self-shielding factors produces a more realistic, but still conservative, approach for managing patient release.

This work compared the predicted dose to an individual due to exposure from a radioactive patient using three models (point, line, and volume), for three therapeutic regimens (hyperthyroidism, thyroid cancer, and non-Hodgkin's lymphoma). For the volume source calculations, Monte Carlo simulations employing the Visual Monte Carlo (VMC) code and the voxel phantom FAX were used. For hyperthyroid patients, the point, line, and volume source models predicted doses to exposed individuals of 54, 24, and 14 mSv, respectively, at a distance of 0.3 m, and 4.8, 4.0 and 3.3 mSv at a distance of 1 m. For thyroid cancer patients, the dose values were 85, 38, and 18 mSv at 0.3 m, and 7.6, 6.4, and 4.4 mSv at 1 m, respectively. For non-Hodgkin's lymphoma (NHL) subjects, the doses were 230, 103, and 36 mSv at 0.3 m, and 21, 17, and 10 mSv at 1 m. These results show that patient release based on point source calculations involves unnecessary conservatism.

The U.S. National Council on Radiation Protection and Measurements and United Nations Scientific Committee on Effects of Atomic Radiation each conducted respective assessments of all radiation sources in the United States and worldwide. The goal of this article is to summarize and combine the results of these two publicly available surveys and to compare the results with historical information. In the United States in 2006, about 377 million diagnostic and interventional radiologic examinations and 18 million nuclear medicine examinations were performed. The United States accounts for about 12% of radiologic procedures and about one-half of nuclear medicine procedures performed worldwide. In the United States, the frequency of diagnostic radiologic examinations has increased almost 10-fold (1950-2006). The U.S. per-capita annual effective dose from medical procedures has increased about sixfold (0.5 mSv [1980] to 3.0 mSv [2006]). Worldwide estimates for 2000-2007 indicate that 3.6 billion medical procedures with ionizing radiation (3.1 billion diagnostic radiologic, 0.5 billion dental, and 37 million nuclear medicine examinations) are performed annually. Worldwide, the average annual per-capita effective dose from medicine (about 0.6 mSv of the total 3.0 mSv received from all sources) has approximately doubled in the past 10-15 years., ((c) RSNA, 2009.)

Basic calculational methods and models used in dose assessment for internal emitters in nuclear medicine are discussed in this overview. Methods for quantification of activity in clinical and preclinical studies also are discussed, and we show how to implement them in currently available dose calculational models. Current practice of the use of internal emitters in therapy also is briefly presented here. Some of the future challenges for dose assessment in nuclear medicine are discussed, including application of patient-specific dose calculational methods and the need for significant advances in radiation biology.

Unlabelled: The technical basis for the dose estimates for several radiopharmaceuticals used in nuclear cardiology is reviewed, and cases in which uncertainty has been encountered in the dosimetry of an agent are discussed. Also discussed is the issue of uncertainties in radiation dose estimates and how to compare the relative risks of studies., Methods: Radiation dose estimates (organ absorbed doses and effective doses) from different literature sources were directly compared. Typical values for administered activity per study were used to compare doses that are to be expected in clinical applications., Results: The effective doses for all agents varied from 2 to 15 mSv per study, with the lowest values being seen for (13)N-NH(3) and (15)O-H(2)O studies and the highest values being seen for (201)Tl-chloride studies. The effective doses for (99m)Tc- and (201)Tl-labeled agents differed by about a factor of 2, a factor that is comparable to the uncertainty in individual values. This uncertainty results from the application of standard anthropomorphic and biokinetic models, presumably representative of the exposed population, to individual patients., Conclusion: Considerations such as diagnostic accuracy, ease of use, image quality, and patient comfort and convenience should generally dictate the choice of a radiopharmaceutical, with radiation dose being only a secondary or even tertiary consideration. Counseling of nuclear medicine patients who may be concerned about exposure should include a reasonable estimate of the median dose for the type of examination and administered activity of the radiopharmaceutical; in addition, it should be explained that the theoretic risks of the procedure are orders of magnitude lower than the actual benefits of the examination. Providing numeric estimates of risks from studies to individual patients is inappropriate, given the uncertainties in the dose estimates and the limited predictive power of current dose-risk models in the low-dose (i.e., diagnostic) range.

In this review, we trace the origins of mathematical modeling methods and pay particular attention to radiotracer applications. Nuclear medicine has been advanced greatly by the efforts of the Society of Nuclear Medicine's Medical Internal Radiation Dose Committee. Well-developed mathematical methods and tools have been created in support of a wide range of applications. Applications of mathematical modeling extend well beyond biology and medicine and are essential to analysis is a wide range of fields that rely on numerical predictions, eg, weather, economic, and various gaming applications. We start with the discovery of radioactivity and radioactive transformations and illustrate selected applications in biology, physiology, and pharmacology. We discuss compartment models as tools used to frame the context of specific problems. A definition of terms, methods, and examples of particular problems follows. We present models of different applications with varying complexity depending on the features of the particular system and function being analyzed. Commonly used analysis tools and methods are described, followed by established models which describe dosimetry along gastrointestinal and urinary excretory pathways, ending finally with a brief discussion of bone marrow dose. We conclude pointing to more recent, promising methods, not yet widely used in dosimetry applications, which aim at coupling pharmacokinetic data with other patient data to correlate patient outcome (benefits and risk) with the type, amount, kind and timing of the therapy the patient received.

Unlabelled: The OLINDA/EXM version 1.0 personal computer code was created as a replacement for the widely used MIRDOSE3.1 code. This paper documents the basic function of the code and how it is similar to and different from the MIRDOSE software., Methods: After creation of the code and alpha- and beta-testing phases, a premarket notification submission (510(k)) was filed with the Food and Drug Administration to permit marketing of the code. Permission was granted in June 2004, and the code is currently being distributed through Vanderbilt University. Not all of the technical details of the dosimetry methods have been shown here, as they have been previously documented., Results: Agreement of doses between the MIRDOSE3.1 and OLINDA/EXM codes was good, within 1%-2% in most cases., Conclusion: The extensive testing of the OLINDA/EXM code, based on comparison with literature-established dose calculations and with the widely tested and accepted MIRDOSE3.1 code, should give users confidence in its output. The OLINDA/EXM code should be easy for MIRDOSE users to adopt and for new users to understand. It will be useful in standardizing and automating internal dose calculations, assessing doses in clinical trials with radiopharmaceuticals, making theoretic calculations for existing pharmaceuticals, teaching, and other purposes.

In nuclear medicine, proper application of radiation protection principles depends on balancing the potential risks of exposure to ionizing radiation against its possible benefits. Average doses to organs, in diagnostic or therapeutic applications, are not always representative of the doses received at the tissue or cellular level. Therefore, understanding of the relationship between the overall biological effect and absorbed dose delivered by the radiopharmaceutical may require study of doses at the organ, tissue, or cell level. In this paper, we review current models for radiation dose assessment, with consideration of the different models and assumptions employed for study at all levels of investigation.

The female nuclear medicine patient is of special concern in evaluating radiation dose and risk in nuclear medicine. The female's overall body size and organ sizes generally are smaller than those of her male counterpart (thus her radiation doses will be higher, given the same amounts of administered activity and similar biokinetics); female gonads are inside the body instead of outside and are near several organs often important as source organs in internal dosimetry (urinary bladder, liver, kidneys, intestines); risk of breast cancer is significantly higher among females than males; and in the case of pregnancy, exposure to radiation of the embryo/fetus and the nursing infant are of special concern in such an analysis. All these concerns are addressed in this study through a comparative study of radiation doses for males and females over a large number (approximately 60) of nuclear medicine studies and through a study of what is known about radiation dosimetry in pregnancy and breast feeding. It was found that women's critical organ doses and effective doses (as defined by the International Commission on Radiological Protection 60 [ICRP 60] are about 25% higher than those for men across all these studies. Women's gonad doses, however, may be as much as 10 to 30 times higher than those in men, although 2- to 3-fold differences are common. Many radiopharmaceuticals are administered to women of childbearing age; however, little is known about how much activity crosses the placenta and about the biokinetics in the fetus should it occur. Nonetheless, dose estimates are provided at four stages of pregnancy (early, 3-month, 6-month, and 9-month gestation) for a large number of radiopharmaceuticals, whether or not quantitative estimates of placental crossover can be made. Many radiopharmaceuticals are also excreted in breast milk of nursing mothers. Breast feeding interruption schedules are suggested through analysis of the observed kinetics of these pharmaceuticals and an assumed dose limit of 1 mSv (effective dose equivalent) to the infant.