Michael Lassmann

EANM/ESC procedural guidelines for myocardial perfusion imaging in nuclear cardiology

The European procedural guidelines for radionuclide imaging of myocardial perfusion and viability are presented in 13 sections covering patient information, radiopharmaceuticals, injected activities and dosimetry, stress tests, imaging protocols and acquisition, quality control and reconstruction methods, gated studies and attenuation-scatter compensation, data analysis, reports and image display, and positron emission tomography. If the specific recommendations given could not be based on evidence from original, scientific studies, we tried to express this state-of-art. The guidelines are designed to assist in the practice of performing, interpreting and reporting myocardial perfusion SPET. The guidelines do not discuss clinical indications, benefits or drawbacks of radionuclide myocardial imaging compared to non-nuclear techniques, nor do they cover cost benefit or cost effectiveness.

Comparison of Empiric Versus Dosimetry-Guided Radioiodine Therapy: The Devil Is in the Details

TO THE EDITOR: We read with interest the article by Deandreis et al. (1) that compared a fixed-activity approach to radioiodine treatment of metastatic differentiated thyroid cancer with a method based on whole-body (blood clearance) dosimetry. Similar survival was seen for both cohorts. This study highlights the continuing uncertainty regarding the lack of an optimal approach to treatment for the highestrisk patients, as recognized by both European Association of Nuclear Medicine and American Thyroid Association guidelines (2,3), and demonstrates the difficulty of performing retrospective analyses. It is notable that despite the apparently substantial differences in treatment regimens and patient cohort characteristics between the two centers, a personalized approach was taken in all cases, with patients in both cohorts receiving highly variable levels of cumulated activity, numbers of treatments, and intervals between administrations. Patient follow-up varied from 5 mo to 31 y. The paper shows that a highly personalized approach is, in oncologic terms, extremely successful in considerably extending the life-span of patients with distant metastases. Likely because of this great success, the comparatively smaller differences, if they exist, between the different approaches to personalization may have been obfuscated. This article appears precisely 80 y after the initial development of radioiodine. The ablation of remnant thyroid after thyroidectomy and the treatment of persistent thyroid disease and distant metastases is surely one of the great success stories of cancer management. The pioneering work of clinician Saul Hertz and physicists Karl Compton and Arthur Roberts, after a luncheon talk entitled “What Physics Can Do for Biology and Medicine” by Dr. Compton in November 1936, demonstrated the enormous potential of the fusion of nuclear physics and medicine and led directly to what is possibly the closest conceivable approach to the magic bullet for cancer (4). Initial studies recognized that the effect of radiation on either healthy or malignant tissue depends on the amount of radiation delivered, and more than 10 y before the development of the Anger camera, great efforts were made to calculate the absorbed doses (in Gy) delivered to thyroid metastases and to healthy organs (5). The work led to the formation of the Radioactive Isotope Research Institute in Boston in September 1946, with Dr. Saul Hertz as the director and Dr. Samuel M. Seidlin as the associate director. In the seminal paper by Seidlin et al. (6) concerning treatment of metastatic thyroid cancer, an empiric activity of 3,700 MBq (100 mCi) of 130I-NaI was administered concomitantly with 760 MBq of 131I-NaI to deliver 90 Gy to the tumor. 130I-NaI was found to cause depression of leukocytes, and future administrations settled on treatment solely with 131I-NaI, although still with an administered activity of 3,700 MBq. This fortuitous combination of the “magic number” with the “magic bullet” paved the way for the use of radiotherapeutics, and the paradigm was applied to most further radiotherapeutics as they were developed. An activity of 3,700 MBq, or multiples thereof, was subsequently administered for the treatment of adult and pediatric neuroendocrine tumors using 131I-metaiodobenzylguanidine, 90Y-DOTATOC, or 177LuDOTATATE; for the initial treatment of liver metastases using 90Y microspheres; and, more recently, for the treatment of bone metastases from prostate cancer using 177Lu-prostate-specific membrane antigen. Highly successful outcomes were reported in the article by Deandreis et al. (1), without apparent correlations either with the whole-body (blood) absorbed doses or with the levels of activity administered. These factors are undoubtedly important but may not be sufficient to generate the improved outcomes that must be available with a more scientific approach. In a dawning era of personalized and precision medicine, radioiodine treatment of differentiated thyroid cancer affords the opportunity to realize the full potential of an individualized approach to treatment that may result in significant patient benefit. This goal can be tackled only by close collaborations between clinicians and medical physicists based on the increasing evidence that outcome depends on the radiation doses delivered rather than on the activities administered (7). The birth of nuclear medicine was blessed with a phenomenally successful cancer treatment by the visionary work of Hertz, Compton, and Roberts. It is surely time to capitalize on their legacy and further improve the treatment—particularly for high-risk and pediatric patients—with the application of imaging and lesion dosimetry in prospective multicenter clinical trials.

Dosimetric Approaches: Current Concepts

Radioiodine therapy with radioactive iodine I-131 is an integral component in the treatment of patients with malignant thyroid disease. Individual dosimetry is useful both therapeutically for the assessment of the associated absorbed doses to the tumour/metastases as well as in selected patients to pre-therapeutically determine the activities to be administered. National and international guidelines recommend methods and mathematical procedures that are applicable for dosimetry, but leave the treating physician unsupported in the interpretation of the results and the therapeutic consequences. The current article provides an overview of the basic principles and methods of dosimetry and indicates how dosimetric assessments in radioiodine therapy can influence the treatment of thyroid carcinoma.

Absorbed dose estimates from a single measurement one to three days after the administration of 177Lu-DOTATATE/-TOC

AIM To retrospectively analyze the accuracy of absorbed dose estimates from a single measurement of the activity concentrations in tumors and relevant organs one to three days after the administration of 177Lu-DOTA-TATE/TOC assuming tissue specific effective half-lives. METHODS Activity kinetics in 54 kidneys, 30 neuroendocrine tumor lesions, 25 livers, and 27 spleens were deduced from series of planar images in 29 patients. After adaptation of mono- or bi-exponential fit functions to the measured data, it was analyzed for each fit function how precise the time integral can be estimated from fixed tissue-specific half-lives and a single measurement at 24, 48, or 72 h after the administration. RESULTS For the kidneys, assuming a fixed tissue-specific half-life of 50 h, the deviations of the estimate from the actual integral were median (5 % percentile, 95 % percentile): -3 °% (-15 %>; +16 °%) for measurements after 24 h, +2 %> (-9 %>; +12 %>) for measurements after 48 h, and 0 % (-2 %; +12 %) for measurements after 72 h. The corresponding values for the other tissues, assuming fixed tissue-specific half-lives of 67 h for liver and spleen and 77 h for tumors, were +2 % (-25 %; +20 %) for measurements after 24 h, +2 °% (-16 %>; +17 %>) for measurements after 48 h, and +2 %> (-11 %>; +10 %>) for measurements after 72 h. CONCLUSIONS Especially for the kidneys, which often represent the dose limiting organ, but also for liver, spleen, and neuroendocrine tumors, a meaningful absorbed dose estimate is possible from a single measurement after 2, more preferably 3 days after the administration of 177Lu-DOTA-TATE/-TOC assuming fixed tissue specific effective half-lives.

Internal Dosimetry: Principles and Applications to NET

In recent years internal dosimetry added valuable information on the diagnostic and therapeutic use of radionuclide imaging and therapy of neuroendocrine tumors.

Radiation Safety and Dosimetry

The use of radioactive substances for sentinel lymph node (SLN) biopsy needs consideration on how to optimize radiation safety issues. In this chapter an overview on basic radiation-related quantities, definitions, and on patient dosimetry is given. Values of absorbed and effective doses are provided for patients, the staff in the operation theater and in the pathology department, and for waste disposal. For radiolocalization of SLN with Tc-99m, the dose to the patients and the exposure of the staff are low; for radiopharmaceuticals with longer half-lives and/or positron emitters, individual monitoring of staff exposure and contamination should be considered for larger patient numbers.

Physics of Radioguided Surgery: Basic Principles and Methods of Radiation Detection

Radioguided surgery requires a significant amount of technology for its implementation. As a result, surgeons working in this field must have a basic know-how that extends beyond the standard surgical training and covers the relevant physics. Within this chapter we have tried to synthesize the background knowledge needed for a complete understanding of the most important aspects and processes. The terminology and the explanations target people just starting in the field, and the contents should prove readily intelligible as long as the complete chapter is read.

Radiation Risk from Medical Exposure in Children

Diagnostic nuclear medicine procedures imply the administration of activity levels that do not lead to the appearance of radiation deterministic effects. Effects to be expected, if at all, are stochastic effects of ionizing radiation. The assessment of adverse health effects from exposure of ionizing radiation in the dose range commonly encountered in clinical (and pediatric) diagnostic nuclear medicine is based on epidemiological and biological data. Most of the data on the effects on human health after exposure to ionizing radiation comes from the Life Span Study of the survivors of the bombings of Hiroshima and Nagasaki, as reported by the Radiation Effects Research Foundation [18, 22–24]. In addition, there are few data on the stochastic radiation risk after treatment of thyroid diseases with radioiodine [10, 21, 26, 31]. However, there is no clear evidence that there is an increase in cancer risk associated with I-131 therapy [31]. No such data are available concerning the potential cancer risk of diagnostic nuclear medicine.