Michael G. Stabin

Radiologic and Nuclear Medicine Studies in the United States and Worldwide: Frequency, Radiation Dose, and Comparison with Other Radiation Sources—1950–2007

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.

Physical models and dose factors for use in internal dose assessment

Abstract— Internal dose assessment depends on the use of mathematical formulas for dose calculation and models of the human body and its organs. A simple, unified method for internal dose calculations is described, which brings together and simplifies concepts used in nuclear medicine and occupational internal dose systems previously described. Using the best current decay data and phantoms for internal dose calculations, dose factors for internal dose assessment are provided. Decay data for over 800 radionuclides from the data service at Brookhaven National Laboratory were combined with absorbed fraction data from a number of currently available mathematical whole body and organ models to provide the dose factors. This represents the first published update on nuclear medicine dose factors since MIRD Pamphlet No. 11 in 1975; in this paper, dose factors for many more nuclides are given (816 vs. 117 in MIRD 11), including some alpha emitters. New models are also employed, and dose factors for bone and marrow have been updated with recently suggested corrections. The good agreement of the new dose factors with previously published values for several of the models gives good confidence in their accuracy. This article gives an overview of the technical basis for these dose factors and some example tables of data, but the bulk of the data files will be distributed electronically. The use of an “electronic publishing” approach permits the publication of this kind of voluminous information in mainstream journals while facilitating rapid access and use without the need to purchase often expensive and bulky paper documents.

SNM Practice Guideline for Sodium 18F-Fluoride PET/CT Bone Scans 1.0

PREAMBLE The Society of Nuclear Medicine (SNM) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. Its 16,000 members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine. In addition to publishing journals, newsletters, and books, the SNM also sponsors international meetings and workshops designed to increase the competencies of nuclear medicine practitioners and to promote new advances in the science of nuclear medicine. The SNM will periodically define new Practice Guidelines for nuclear medicine practice to help advance the science of nuclear medicine and to improve the quality of service to patients throughout the United States. Existing Practice Guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each Practice Guideline, representing a policy statement by the SNM, has undergone a thorough consensus process in which it has been subjected to extensive review, requiring the approval of the Committee on SNM Guidelines, Health Policy and Practice Commission, and SNM Board of Directors. The Practice Guidelines recognize that the safe and effective use of diagnostic nuclear medicine imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published Practice Guidelines by those entities not providing these services is not authorized. These Practice Guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNM cautions against the use of these Practice Guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, an approach that differs from the Practice Guidelines, standing alone, does not necessarily imply that the approach was below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the Practice Guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the Practice Guidelines. The practice of medicine involves not only the science, but also the art, of preventing, diagnosing, alleviating, and treating disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these Practice Guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these Practice Guidelines is to assist practitioners in achieving this objective.

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.

Biokinetics and dosimetry in patients administered with 111In-DOTA-Tyr3-octreotide: implications for internal radiotherapy with 90Y-DOTATOC

Abstract. Recent advances in receptor-mediated tumour imaging have resulted in the development of a new somatostatin analogue, DOTA-dPhe1-Tyr3-octreotide. This new compound, named DOTATOC, has shown high affinity for somatostatin receptors, ease of labelling and stability with yttrium-90 and favourable biodistribution in animal models. The aim of this work was to evaluate the biodistribution and dosimetry of DOTATOC radiolabelled with indium-111, in anticipation of therapy trials with 90Y-DOTATOC in patients. Eighteen patients were injected with DOTATOC (10 µg), labelled with 150–185 MBq of 111In. Blood and urine samples were collected throughout the duration of the study (0–2 days). Planar and single-photon emission tomography images were acquired at 0.5, 3–4, 24 and 48 h and time-activity curves were obtained for organs and tumours. A compartmental model was used to determine the kinetic parameters for each organ. Dose calculations were performed according to the MIRD formalism. Specific activities of >37 GBq/ µmol were routinely achieved. Patients showed no acute or delayed adverse reactions. The residence time for 111In-DOTATOC in blood was 0.9±0.4 h. The injected activity excreted in the urine in the first 24 h was 73%±11%. The agent localized primarily in spleen, kidneys and liver. The residence times in source organs were: 2.2±1.8 h in spleen, 1.7±1.2 h in kidneys, 2.4±1.9 h in liver, 1.5±0.3 h in urinary bladder and 9.4±5.5 h in the remainder of the body; the mean residence time in tumour was 0.47 h (range: 0.03–6.50 h). Based on our findings, the predicted absorbed doses for 90Y-DOTATOC would be 7.6±6.3 (spleen), 3.3±2.2 (kidneys), 0.7±0.6 (liver), 2.2±0.3 (bladder), 0.03±0.01 (red marrow) and 10.1 (range: 1.4–31.0) (tumour) mGy/MBq. These results indicate that high activities of 90Y-DOTATOC can be administered with low risk of myelotoxicity, although with potentially high radiation doses to the spleen and kidneys. Tumour doses were high enough in most cases to make it likely that the disired therapeutic response desired would be obtained.

Recommendations of the American Association of Physicists in Medicine on dosimetry, imaging, and quality assurance procedures for 90Y microsphere brachytherapy in the treatment of hepatic malignancies.

Yttrium-90 microsphere brachytherapy of the liver exploits the distinctive features of the liver anatomy to treat liver malignancies with beta radiation and is gaining more wide spread clinical use. This report provides a general overview of microsphere liver brachytherapy and assists the treatment team in creating local treatment practices to provide safe and efficient patient treatment. Suggestions for future improvements are incorporated with the basic rationale for the therapy and currently used procedures. Imaging modalities utilized and their respective quality assurance are discussed. General as well as vendor specific delivery procedures are reviewed. The current dosimetry models are reviewed and suggestions for dosimetry advancement are made. Beta activity standards are reviewed and vendor implementation strategies are discussed. Radioactive material licensing and radiation safety are discussed given the unique requirements of microsphere brachytherapy. A general, team-based quality assurance program is reviewed to provide guidance for the creation of the local procedures. Finally, recommendations are given on how to deliver the current state of the art treatments and directions for future improvements in the therapy.

First-in-Man Evaluation of 2 High-Affinity PSMA-Avid Small Molecules for Imaging Prostate Cancer

This phase 1 study was performed to determine the pharmacokinetics and ability to visualize prostate cancer in bone, soft-tissue, and the prostate gland using 123I-MIP-1072 and 123I-MIP-1095, novel radiolabeled small molecules targeting prostate-specific membrane antigen. Methods: Seven patients with a documented history of prostate cancer by histopathology or radiologic evidence of metastatic disease were intravenously administered 370 MBq (10 mCi) of 123I-MIP-1072 and 123I-MIP-1095 2 wk apart in a crossover trial design. 123I-MIP-1072 was also studied in 6 healthy volunteers. Whole-body planar and SPECT/CT imaging was performed and pharmacokinetics studied over 2–3 d. Target-to-background ratios were calculated. Absorbed radiation doses were estimated using OLINDA/EXM. Results: 123I-MIP-1072 and 123I-MIP-1095 visualized lesions in soft tissue, bone, and the prostate gland within 0.5–1 h after injection, with retention beyond 48 h. Target-to-background ratios from planar images averaged 2:1 at 1 h, 3:1 at 4–24 h, and greater than 10:1 at 4 and 24 h for SPECT/CT. Both agents cleared the blood in a biphasic manner; clearance of 123I-MIP-1072 was approximately 5 times faster. 123I-MIP-1072 was excreted in the urine, with 54% and 74% present by 24 and 72 h, respectively. In contrast, only 7% and 20% of 123I-MIP-1095 had been renally excreted by 24 and 72 h, respectively. Estimated absorbed radiation doses were 0.054 versus 0.110 mGy/MBq for the kidneys and 0.024 versus 0.058 mGy/MBq for the liver, for 123I-MIP-1072 and 123I-MIP-1095, respectively. Conclusion: 123I-MIP-1072 and 123I-MIP-1095 detect lesions in soft tissue, bone, and the prostate gland at as early as 1–4 h. These novel radiolabeled small molecules have excellent pharmacokinetic and pharmacodynamic profiles and warrant further development as diagnostic and potentially when labeled with 131I therapeutic radiopharmaceuticals.

Radiation absorbed dose to the embryo/fetus from radiopharmaceuticals.

Radiation protection practice requires the knowledge of estimated absorbed radiation doses to aid in the understanding of the potential detriment of various exposures. In nuclear medicine, the radiation doses to the internal organs of the subject are commonly calculated using the MIRD methods and equations. The absorbed dose to the embryo or fetus has long been an area of concern. The recent release of the pregnant female phantom series, and its incorporation into the MIRDOSE 3 computer software, has made possible the estimation of absorbed doses from radionuclides in the body to the fetus in early pregnancy and at 3, 6, and 9 mo gestation. A survey of several major medical institutions was made to determine the radiopharmaceuticals which might be given, whether intentionally or not, to women of childbearing years. Biokinetic data for these radiopharmaceuticals were gathered from various documents and other resources, and the absorbed doses to the embryo and fetus at these different stages of gestation from radiations originating within the mothers organs were estimated. In addition, information about activity distributed within the placenta and fetus was included where quantitative data were available. These absorbed dose estimates can be used to evaluate the risk associated with the use of different radiopharmaceuticals so that a more informed evaluation of the risks and benefits of the different procedures may be made. Further research is needed into the mechanisms and quantitative aspects of the placental transfer of many radiopharmaceuticals.

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.

Uncertainties in Internal Dose Calculations for Radiopharmaceuticals

This paper presents a systematic analysis of the inherent uncertainty in internal dose calculations for radiopharmaceuticals. A generic equation for internal dose is presented, and the uncertainty in each of the individual terms is analyzed, with the relative uncertainty of all terms compared. The combined uncertainties in most radiopharmaceutical dose estimates will be typically at least a factor of 2 and may be considerably greater. In therapy applications, if patient-individualized absorbed doses are calculated, with attention being paid to accurate data gathering and analysis and measurement of individual organ volumes, many of the model-based uncertainties can be removed, and the total uncertainty in an individual dose estimate can be reduced to a value of perhaps ±10%–20%. Radiation dose estimates for different diagnostic radiopharmaceuticals should be appreciated and considered, but small differences in dose estimates between radiopharmaceuticals should not be given too much importance when one is choosing radiopharmaceuticals for general clinical use. Diagnostic accuracy, ease of use, image quality, patient comfort, and other similar factors should predominate in the evaluation, with radiation dose being another issue considered while balancing risks and benefits appropriately.