The relation between cardiac 123I-mIBG scintigraphy and functional response 1 year after CRT implantation

Cardiac resynchronization therapy (CRT) is a disease-modifying therapy in patients with chronic heart failure (CHF). Current guidelines ascribe CRT eligibility on three parameters only: left ventricular ejection fraction (LVEF), QRS duration, and New York Heart Association (NYHA) functional class. However, one-third of CHF patients does not benefit from CRT. This study evaluated whether 123I-meta-iodobenzylguanidine (123I-mIBG) assessed cardiac sympathetic activity could optimize CRT patient selection

Sheep can be used as animal model of regional myocardial remodeling and controllable work

Background: Pacing the right heart has been shown to induce reversible conduction delay and subse­quent asymmetric remodeling of the left ventricle (LV) in dogs and pigs. Both species have disadvantages in animal experiments. Therefore the aim of this study was to develop a more feasible and easy-to-use animal model in sheep. Methods: Dual-chamber (DDD) pacemakers with epicardial leads on the right atrium and right ven­tricular free wall were implanted in 13 sheep. All animals underwent 8 weeks of chronic rapid pacing at 180 bpm. Reported observations were made at 110 bpm. Results: DDD pacing acutely induced a left bundle branch block (LBBB) — like pattern with almost doubling in QRS width and the appearance of a septal flash, indicating mechanical dyssynchrony. Atrial pacing (AAI) resulted in normal ventricular conduction and function. During 8 weeks of rapid DDD pacing, animals developed LV remodeling (confirmed with histology) with septal wall thinning (–30%, p < 0.05), lateral wall thickening (+22%, p < 0.05), LV volume increase (+32%, p < 0.05), decrease of LV ejection fraction (–31%, p < 0.05), and functional mitral regurgitation. After 8 weeks, segmental pressure-strain-loops, representing regional myocardial work, were recorded. Switching from AAI to DDD pacing decreased immediately work in the septum and increased it in the lateral wall (–69 and +41%, respectively, p < 0.05). Global LV stroke work and dP/dtmax decreased (–27% and -25%, respectively, p < 0.05). Conclusions: This study presents the development a new sheep model with an asymmetrically remod­eled LV. Simple pacemaker programing allows direct modulation of regional myocardial function and work. This animal model provides a new and valuable alternative for canine or porcine models and has the potential to become instrumental for investigating regional function and loading conditions on regional LV remodeling

Consensus document for the diagnosis of prosthetic joint infections. a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement)

Background: For the diagnosis of prosthetic joint infection, real evidence-based guidelines to aid clinicians in choosing the most accurate diagnostic strategy are lacking. Aim and Methods: To address this need, we performed a multidisciplinary systematic review of relevant nuclear medicine, radiological, orthopaedic, infectious, and microbiological literature to define the diagnostic accuracy of each diagnostic technique and to address and provide evidence-based answers on uniform statements for each topic that was found to be important to develop a commonly agreed upon diagnostic flowchart. Results and Conclusion: The approach used to prepare this set of multidisciplinary guidelines was to define statements of interest and follow the procedure indicated by the Oxford Centre for Evidence-based Medicine (OCEBM)

The human somatostatin receptor type 2 as an imaging and suicide reporter gene for pluripotent stem cell-derived therapy of myocardial infarction

Rationale: Pluripotent stem cells (PSCs) are being investigated as a cell source for regenerative medicine since they provide an infinitive pool of cells that are able to differentiate towards every cell type of the body. One possible therapeutic application involves the use of these cells to treat myocardial infarction (MI), a condition where billions of cardiomyocytes (CMs) are lost. Although several protocols have been developed to differentiate PSCs towards CMs, none of these provide a completely pure population, thereby still posing a risk for neoplastic teratoma formation. Therefore, we developed a strategy to (i) monitor cell behavior noninvasively via site-specific integration of firefly luciferase (Fluc) and the human positron emission tomography (PET) imaging reporter genes, sodium iodide symporter (hNIS) and somatostatin receptor type 2 (hSSTr2), and (ii) perform hSSTr2-mediated suicide gene therapy via the clinically used radiopharmacon 177Lu-DOTATATE. Methods: Human embryonic stem cells (ESCs) were gene-edited via zinc finger nucleases to express Fluc and either hNIS or hSSTr2 in the safe harbor locus, adeno-associated virus integration site 1. Firstly, these cells were exposed to 4.8 MBq 177Lu-DOTATATE in vitro and cell survival was monitored via bioluminescence imaging (BLI). Afterwards, hNIS+ and hSSTr2+ ESCs were transplanted subcutaneously and teratomas were allowed to form. At day 59, baseline 124I and 68Ga-DOTATATE PET and BLI scans were performed. The day after, animals received either saline or 55 MBq 177Lu-DOTATATE. Weekly BLI scans were performed, accompanied by 124I and 68Ga-DOTATATE PET scans at days 87 and 88, respectively. Finally, hSSTr2+ ESCs were differentiated towards CMs and transplanted intramyocardially in the border zone of an infarct that was induced by left anterior descending coronary artery ligation. After transplantation, the animals were monitored via BLI and PET, while global cardiac function was evaluated using cardiac magnetic resonance imaging. Results: Teratoma growth of both hNIS+ and hSSTr2+ ESCs could be followed noninvasively over time by both PET and BLI. After 177Lu-DOTATATE administration, successful cell killing of the hSSTr2+ ESCs was achieved both in vitro and in vivo, indicated by reductions in total tracer lesion uptake, BLI signal and teratoma volume. As undifferentiated hSSTr2+ ESCs are not therapeutically relevant, they were differentiated towards CMs and injected in immune-deficient mice with a MI. Long-term cell survival could be monitored without uncontrolled cell proliferation. However, no improvement in the left ventricular ejection fraction was observed.Conclusion: We developed isogenic hSSTr2-expressing ESCs that allow noninvasive cell monitoring in the context of PSC-derived regenerative therapy. Furthermore, we are the first to use the hSSTr2 not only as an imaging reporter gene, but also as a suicide mechanism for radionuclide therapy in the setting of PSC-derived cell treatment

Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0

PURPOSE: The goal of this guideline/procedure standard is to assist nuclear medicine physicians, other nuclear medicine professionals, oncologists or other medical specialists for recommended use of [ METHODS: In a cooperative effort between the EANM, the SNMMI and the ANZSNM, clinical indications, recommended imaging procedures and reporting standards have been agreed upon and summarized in this joint guideline/procedure standard. CONCLUSIONS: The field of immuno-oncology is rapidly evolving, and this guideline/procedure standard should not be seen as definitive, but rather as a guidance document standardizing the use and interpretation of [ PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association founded in 1985 to facilitate worldwide communication among individuals pursuing clinical and academic excellence in nuclear medicine. The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote science, technology and practical application of nuclear medicine. The Australian and New Zealand Society of Nuclear Medicine (ANZSNM), founded in 1969, represents the major professional society fostering the technical and professional development of nuclear medicine practice across Australia and New Zealand. It promotes excellence in the nuclear medicine profession through education, research and a commitment to the highest professional standards. EANM, SNMMI and ANZSNM members are physicians, technologists, physicists and scientists specialized in the research and clinical practice of nuclear medicine. All three societies will periodically put forth new standards/guidelines for nuclear medicine practice to help advance the science of nuclear medicine and improve service to patients. Existing standards/guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each standard/guideline, representing a policy statement by the EANM/SNMMI/ANZSNM, has undergone a thorough consensus process, entailing extensive review. These societies recognize that the safe and effective use of diagnostic nuclear medicine imaging requires particular training and skills, as described in each document. These standards/guidelines are educational tools designed to assist practitioners in providing appropriate and effective nuclear medicine care for patients. These guidelines are consensus documents based on current knowledge. They are not intended to be inflexible rules or requirements of practice, nor should they be used to establish a legal standard of care. For these reasons and those set forth below, the EANM, SNMMI and ANZSNM caution against the use of these standards/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 medical professionals considering the unique circumstances of each case. Thus, there is no implication that an action differing from what is laid out in the guidelines/procedure standards, standing alone, is below standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the standards/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 guidelines/procedure standards. The practice of medicine involves not only the science, but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible for general guidelines to consistently allow for an accurate diagnosis to be reached or a particular treatment response to be predicted. Therefore, it should be recognized that adherence to these standards/ guidelines will not ensure a successful outcome. All that should be expected is that practitioners follow a reasonable course of action, based on their level of training, current knowledge, clinical practice guidelines, available resources and the needs/context of the patient being treated. The sole purpose of these guidelines is to assist practitioners in achieving this objective. The present guideline/procedure standard was developed collaboratively by the EANM, the SNMMI and the ANZSNM, with the support of international experts in the field. They summarize also the views of the Oncology and Theranostics and the Inflammation and Infection Committees of the EANM, as well as the procedure standards committee of the SNMMI, and reflect recommendations for which the EANM and SNMMI cannot be held responsible. The recommendations should be taken into the context of good practice of nuclear medicine and do not substitute for national and international legal or regulatory provisions

Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation (4Is)-related cardiovascular diseases: a joint collaboration of the EACVI and the EANM

With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using [18F]FDG, but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications

Consensus document for the diagnosis of prosthetic joint infections: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement).

For the diagnosis of prosthetic joint infection, real evidence-based guidelines to aid clinicians in choosing the most accurate diagnostic strategy are lacking. To address this need, we performed a multidisciplinary systematic review of relevant nuclear medicine, radiological, orthopaedic, infectious, and microbiological literature to define the diagnostic accuracy of each diagnostic technique and to address and provide evidence-based answers on uniform statements for each topic that was found to be important to develop a commonly agreed upon diagnostic flowchart. The approach used to prepare this set of multidisciplinary guidelines was to define statements of interest and follow the procedure indicated by the Oxford Centre for Evidence-based Medicine (OCEBM)

Consensus document for the diagnosis of peripheral bone infection in adults: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement).

In adults with a suspicion of peripheral bone infection, evidence-based guidelines in choosing the most accurate diagnostic strategy are lacking. To provide an evidence-based, multidisciplinary consensus document on the diagnostic management of adult patients with PBIs, we performed a systematic review of relevant infectious, microbiological, orthopedic, radiological, and nuclear medicine literature. Delegates from four European societies (European Bone and Joint Infection Society, European Society of Microbiology and Infectious Diseases, European Society or Radiology, and European Association of Nuclear Medicine) defined clinical questions to be addressed, thoroughly reviewed the literature pertinent to each of the questions, and thereby evaluated the diagnostic accuracy of each diagnostic technique. Inclusion of the papers per statement was based on a PICO (Population/problem - Intervention/indicator - Comparator - Outcome) question following the strategy reported by the Oxford Centre for Evidence-based Medicine. For each statement, the level of evidence was graded according to the 2011 review of the Oxford Centre for Evidence-based Medicine. All approved statements were addressed taking into consideration the available diagnostic procedures, patient acceptance, tolerability, complications, and costs in Europe. Finally, a commonly agreed-upon diagnostic flowchart was developed