Joint EANM/SIOPE/RAPNO practice guidelines/SNMMI procedure standards for imaging of paediatric gliomas using PET with radiolabelled amino acids and [18F]FDG: version 1.0.

Positron emission tomography (PET) has been widely used in paediatric oncology. 2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is the most commonly used radiopharmaceutical for PET imaging. For oncological brain imaging, different amino acid PET radiopharmaceuticals have been introduced in the last years. The purpose of this document is to provide imaging specialists and clinicians guidelines for indication, acquisition, and interpretation of [18F]FDG and radiolabelled amino acid PET in paediatric patients affected by brain gliomas. There is no high level of evidence for all recommendations suggested in this paper. These recommendations represent instead the consensus opinion of experienced leaders in the field. Further studies are needed to reach evidence-based recommendations for the applications of [18F]FDG and radiolabelled amino acid PET in paediatric neuro-oncology. These recommendations are not intended to be a substitute for national and international legal or regulatory provisions and should be considered in the context of good practice in nuclear medicine. The present guidelines/standards were developed collaboratively by the EANM and SNMMI with the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group and the Response Assessment in Paediatric Neuro-Oncology (RAPNO) working group. They summarize also the views of the Neuroimaging and Oncology and Theranostics Committees of the EANM and reflect recommendations for which the EANM and other societies cannot be held responsible.

Development and autoregulation of kidney function in children: a retrospective study using 99mTc-MAG3 renography.

BACKGROUND: Both the development of kidney function in healthy children and autoregulation ability of kidney function in patients with asymmetric kidneys are important in clinical diagnosis and treatment of kidney-related diseases, but there are however only limited studies. This study aimed to investigate development of kidney function in normal children with healthy symmetric kidneys and autoregulation of the healthy kidney compensating the functional loss of a diseased one in children with asymmetric kidneys. METHODS: Two hundred thirty-seven children (156 male, 81 female) from 0 to 20y (average 4.6y ± 5.1) undergoing 99mTc-MAG3 renography were included, comprising 134 with healthy symmetrically functioning kidneys and 103 with asymmetric kidneys. Clearance was calculated from kidney uptakes at 1-2 min. A developmental model between MAG3 clearance (CL) and patient age in normal group was identified (CL = 84.39Age0.395 ml/min, r = 0.957, p < 0.001). The clearance autoregulation rate in abnormal group with asymmetric kidneys was defined as the ratio of the measured MAG3 clearance and the normal value predicted from the renal developmental model of normal group. RESULTS: No significant difference of MAG3 clearance (p = 0.723) was found between independent abnormal group and normal group. The autoregulation rate of kidney clearance in abnormal group was 94.2% on average, and no significant differences were found between two age groups (p = 0.49), male and female (p = 0.39), and left kidney and right kidney (p = 0.92) but two different grades of asymmetric kidneys (p = 0.02). CONCLUSIONS: The healthy kidney of two asymmetric kidneys can automatically regulate total kidney function up to 94% of two symmetric kidneys in normal children.

Radiation Dose to Pediatric Patients From Radiopharmaceuticals.

Nuclear medicine provides methods and techniques in that has benefited pediatric patients and their referring physicians for over 40 years. Nuclear medicine provides qualitative and quantitative information about overall and regional function of organs, systems, and lesions in the body. This involves applications in many organ systems including the skeleton, the brain, the kidneys and the heart as well as in the diagnosis and treatment of cancer. The practice of nuclear medicine requires the administration of radiopharmaceuticals which expose the patient to very low levels of ionizing radiation. Advanced approaches in the estimation of radiation dose from the internal distribution of radiopharmaceuticals in patients of various sizes and shapes have been developed in the past 20 years. Although there is considerable uncertainty in the estimation of the risk of adverse health effects from radiation at the very low exposure levels typically associated with nuclear medicine, some considers it prudent to be more cautious when applied to children as they are generally considered to be at higher risk than adults. Standard guidelines for administered activities for nuclear medicine procedures in children have been established including the North American consensus guidelines and the Paediatric Dosage Card developed by the European Association of Nuclear Medicine. As we move into the future, these guidelines would likely be reviewed in response to changes in clinical practice, a better understanding of radiation dosimetry as applied to children as well as new clinical applications, new advancements in the field with respect to both instrumentation and image reconstruction and processing.

Celebrating eighty years of radionuclide therapy and the work of Saul Hertz.

March 2021 will mark the eightieth anniversary of targeted radionuclide therapy, recognizing the first use of radioactive iodine to treat thyroid disease by Dr. Saul Hertz on March 31, 1941. The breakthrough of Dr. Hertz and collaborator physicist Arthur Roberts was made possible by rapid developments in the fields of physics and medicine in the early twentieth century. Although diseases of the thyroid gland had been described for centuries, the role of iodine in thyroid physiology had been elucidated only in the prior few decades. After the discovery of radioactivity by Henri Becquerel in 1897, rapid advancements in the field, including artificial production of radioactive isotopes, were made in the subsequent decades. Finally, the diagnostic and therapeutic use of radioactive iodine was based on the tracer principal that was developed by George de Hevesy. In the context of these advancements, Hertz was able to conceive the potential of using of radioactive iodine to treat thyroid diseases. Working with Dr. Roberts, he obtained the experimental data and implemented it in the clinical setting. Radioiodine therapy continues to be a mainstay of therapy for hyperthyroidism and thyroid cancer. However, Hertz struggled to gain recognition for his accomplishments and to continue his work and, with his early death in 1950, his contributions have often been overlooked until recently. The work of Hertz and others provided a foundation for the introduction of other radionuclide therapies and for the development of the concept of theranostics.

Body morphometry appropriate computational phantoms for dose and risk optimization in pediatric renal imaging with Tc-99m DMSA and Tc-99m MAG3.

Current guidelines for administered activity (AA) in pediatric nuclear medicine imaging studies are based on a 2016 harmonization of the 2010 North American Consensus guidelines and the 2007 European Association of Nuclear Medicine pediatric dosage card. These guidelines assign AA scaled to patient body mass, with further constraints on maximum and minimum values of radiopharmaceutical activity. These guidelines, however, are not formulated based upon a rigor-ous evaluation of diagnostic image quality. In a recent study of the renal cortex imaging agent 99mTc-DMSA (Li Y et al 2019), body mass-based dosing guidelines were shown to not give the same level of image quality for patients of differing body mass. Their data suggest that patient girth at the level of the kidneys may be a better morphometric parameter to consider when selecting AA for renal nuclear medicine imaging. The objective of the present work was thus to develop a dedicated series of computational phantoms to support image quality and organ dose studies in pediatric renal imaging using 99mTc-DMSA or 99mTc-MAG3. The final library consists of 50 male and female phantoms of ages 0 to 15 years, with percentile variations (5th to 95th) in waist circumference (WC) at each age. For each phantom, nominal values of kidney volume, length, and depth were incorporated into the phantom design. Organ absorbed doses, detriment-weighted doses, and stochastic risks were assessed using ICRP reference biokinetic models for both agents. In Monte Carlo radiation transport simulations, organ doses for these agents yielded detriment-weighted dose coefficients (mSv/MBq) that were in general larger than current ICRP values of the effective dose coefficients (age and WC-averaged ratios of eDW/e were 1.40 for the male phantoms and 1.49 for the female phantoms). Values of risk index (ratio of radiation-induced to natural background cancer incidence risk x 100) varied between 0.062 (newborns) to 0.108 (15-year-olds) for 99mTc-DMSA and between 0.026 (newborns) to 0.122 (15-year-olds) for 99mTc-MAG3. Using tallies of photon exit fluence as a rough surrogate for uniform image quality, our study demonstrated that through body region-of-interest optimization of AA, there is the potential for further dose and risk reductions of between factors of 1.5 to 3.0 beyond simple weight-based dosing guidance.

Re-evaluation of pediatric 18F-FDG dosimetry: Cristy-Eckerman versus UF/NCI hybrid computational phantoms.

Because of the concerns associated with radiation exposure at a young age, there is an increased interest in pediatric absorbed dose estimates for imaging agents. Almost all reported pediatric absorbed dose estimates, however, have been determined using adult pharmacokinetic data with radionuclide S values that take into account the anatomical differences between adults and children based upon the older Cristy-Eckerman (C-E) stylized phantoms. In this work, we use pediatric model-derived pharmacokinetics to compare absorbed dose and effective dose estimates for 18F-FDG in pediatric patients using S values generated from two different geometries of computational phantoms. Time-integrated activity coefficients of 18F-FDG in brain, lungs, heart wall, kidneys and liver, retrospectively, calculated from 35 pediatric patients at the Boston's Children Hospital were used. The absorbed dose calculation was performed in accordance with the Medical Internal Radiation Dose method using S values generated from the University of Florida/National Cancer Institute (UF/NCI) hybrid phantoms, as well as those from C-E stylized computational phantoms. The effective dose was computed using tissue-weighting factors from ICRP Publication 60 and ICRP Publication 103 for the C-E and UF/NCI, respectively. Substantial differences in the absorbed dose estimates between UF/NCI hybrid pediatric phantoms and the C-E stylized phantoms were found for the lungs, ovaries, red bone marrow and urinary bladder wall. Large discrepancies in the calculated dose values were observed in the bone marrow; ranging between -26% to +199%. The effective doses computed by the UF/NCI hybrid phantom S values were slightly different than those seen using the C-E stylized phantoms with percent differences of -0.7%, 2.9% and 2.5% for a newborn, 1 year old and 5 year old, respectively. Differences in anatomical modeling features among computational phantoms used to perform Monte Carlo-based photon and electron transport simulations for 18F, and very likely for other radionuclides, impact internal organ dosimetry computations for pediatric nuclear medicine studies.

How we read pediatric PET/CT: indications and strategies for image acquisition, interpretation and reporting.

PET/CT plays an important role in the diagnosis, staging and management of many pediatric malignancies. The techniques for performing PET/CT examinations in children have evolved, with increasing attention focused on reducing patient exposure to ionizing radiation dose whenever possible and minimizing scan duration and sedation times, with a goal toward optimizing the overall patient experience. This review outlines our approach to performing PET/CT, including a discussion of the indications for a PET/CT exam, approaches for optimizing the exam protocol, and a review of different approaches for acquiring the CT portion of the PET/CT exam. Strategies for PACS integration, image display, interpretation and reporting are also provided. Most practices will develop a strategy for performing PET/CT that best meets their respective needs. The purpose of this article is to provide a comprehensive overview for radiologists who are new to pediatric PET/CT, and also to provide experienced PET/CT practitioners with an update on state-of-the art CT techniques that we have incorporated into our protocols and that have enabled us to make considerable improvements to our PET/CT practice.

Appropriate Use of Effective Dose in Radiation Protection and Risk Assessment.

Effective dose was introduced by the ICRP for the single, over-arching purpose of setting limits for radiation protection. Effective dose is a derived quantity or mathematical construct and not a physical, measurable quantity. The formula for calculating effective dose to a reference model incorporates terms to account for all radiation types, organ and tissue radiosensitivities, population groups, and multiple biological endpoints. The properties and appropriate applications of effective dose are not well understood by many within and outside the health physics profession; no other quantity in radiation protection has been more confusing or misunderstood. According to ICRP Publication 103, effective dose is to be used for "prospective dose assessment for planning and optimization in radiological protection, and retrospective demonstration of compliance for regulatory purposes." In practice, effective dose has been applied incorrectly to predict cancer risk among exposed persons. The concept of effective dose applies generally to reference models only and not to individual subjects. While conceived to represent a measure of cancer risk or heritable detrimental effects, effective dose is not predictive of future cancer risk. The formula for calculating effective dose incorporates committee-selected weighting factors for radiation quality and organ sensitivity; however, the organ weighting factors are averaged across all ages and both genders and thus do not apply to any specific individual or radiosensitive subpopulations such as children and young women. Further, it is not appropriate to apply effective dose to individual medical patients because patient-specific parameters may vary substantially from the assumptions used in generalized models. Also, effective dose is not applicable to therapeutic uses of radiation, as its mathematical underpinnings pertain only to observed late (stochastic) effects of radiation exposure and do not account for short-term adverse tissue reactions. The weighting factors incorporate substantial uncertainties, and linearity of the dose-response function at low dose is uncertain and highly disputed. Since effective dose is not predictive of future cancer incidence, it follows that effective dose should never be used to estimate future cancer risk from specific sources of radiation exposure. Instead, individual assessments of potential detriment should only be based on organ or tissue radiation absorbed dose, together with best scientific understanding of the corresponding dose-response relationships.

Correlation of 18F-FDG PET and MRI Apparent Diffusion Coefficient Histogram Metrics with Survival in Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium.

The purpose of this study was to describe baseline 18F-FDG PET voxel characteristics in pediatric diffuse intrinsic pontine glioma (DIPG) and to correlate these metrics with baseline MRI apparent diffusion coefficient (ADC) histogram metrics, progression-free survival (PFS), and overall survival. Methods: Baseline brain 18F-FDG PET and MRI scans were obtained in 33 children from Pediatric Brain Tumor Consortium clinical DIPG trials. 18F-FDG PET images, postgadolinium MR images, and ADC MR images were registered to baseline fluid attenuation inversion recovery MR images. Three-dimensional regions of interest on fluid attenuation inversion recovery MR images and postgadolinium MR images and 18F-FDG PET and MR ADC histograms were generated. Metrics evaluated included peak number, skewness, and kurtosis. Correlation between PET and MR ADC histogram metrics was evaluated. PET pixel values within the region of interest for each tumor were plotted against MR ADC values. The association of these imaging markers with survival was described. Results: PET histograms were almost always unimodal (94%, vs. 6% bimodal). None of the PET histogram parameters (skewness or kurtosis) had a significant association with PFS, although a higher PET postgadolinium skewness tended toward a less favorable PFS (hazard ratio, 3.48; 95% confidence interval [CI], 0.75-16.28 [P = 0.11]). There was a significant association between higher MR ADC postgadolinium skewness and shorter PFS (hazard ratio, 2.56; 95% CI, 1.11-5.91 [P = 0.028]), and there was the suggestion that this also led to shorter overall survival (hazard ratio, 2.18; 95% CI, 0.95-5.04 [P = 0.067]). Higher MR ADC postgadolinium kurtosis tended toward shorter PFS (hazard ratio, 1.30; 95% CI, 0.98-1.74 [P = 0.073]). PET and MR ADC pixel values were negatively correlated using the Pearson correlation coefficient. Further, the level of PET and MR ADC correlation was significantly positively associated with PFS; tumors with higher values of ADC-PET correlation had more favorable PFS (hazard ratio, 0.17; 95% CI, 0.03-0.89 [P = 0.036]), suggesting that a higher level of negative ADC-PET correlation leads to less favorable PFS. A more significant negative correlation may indicate higher-grade elements within the tumor leading to poorer outcomes. Conclusion:18F-FDG PET and MR ADC histogram metrics in pediatric DIPG demonstrate different characteristics with often a negative correlation between PET and MR ADC pixel values. A higher negative correlation is associated with a worse PFS, which may indicate higher-grade elements within the tumor.

Dose Estimation in Pediatric Nuclear Medicine.

The practice of nuclear medicine in children is well established for imaging practically all physiologic systems but particularly in the fields of oncology, neurology, urology, and orthopedics. Pediatric nuclear medicine yields images of physiologic and molecular processes that can provide essential diagnostic information to the clinician. However, nuclear medicine involves the administration of radiopharmaceuticals that expose the patient to ionizing radiation and children are thought to be at a higher risk for adverse effects from radiation exposure than adults. Therefore it may be considered prudent to take extra care to optimize the radiation dose associated with pediatric nuclear medicine. This requires a solid understanding of the dosimetry associated with the administration of radiopharmaceuticals in children. Models for estimating the internal radiation dose from radiopharmaceuticals have been developed by the Medical Internal Radiation Dosimetry Committee of the Society of Nuclear Medicine and Molecular Imaging and other groups. But to use these models accurately in children, better pharmacokinetic data for the radiopharmaceuticals and anatomical models specifically for children need to be developed. The use of CT in the context of hybrid imaging has also increased significantly in the past 15 years, and thus CT dosimetry as it applies to children needs to be better understood. The concept of effective dose has been used to compare different practices involving radiation on a dosimetric level, but this approach may not be appropriate when applied to a population of children of different ages as the radiosensitivity weights utilized in the calculation of effective dose are not specific to children and may vary as a function of age on an organ-by-organ bias. As these gaps in knowledge of dosimetry and radiation risk as they apply to children are filled, more accurate models can be developed that allow for better approaches to dose optimization. In turn, this will lead to an overall improvement in the practice of pediatric nuclear medicine by providing excellent diagnostic image quality at the lowest radiation dose possible.

A risk index for pediatric patients undergoing diagnostic imaging with (99m)Tc-dimercaptosuccinic acid that accounts for body habitus.

Published guidelines for administered activity to pediatric patients undergoing diagnostic nuclear medicine imaging are currently obtained through expert consensus of the minimum values as a function of body weight as required to yield diagnostic quality images. We have previously shown that consideration of body habitus is also important in obtaining diagnostic quality images at the lowest administered activity. The objective of this study was to create a series of computational phantoms that realistically portray the anatomy of the pediatric patient population which can be used to develop and validate techniques to minimize radiation dose while maintaining adequate image quality. To achieve this objective, we have defined an imaging risk index that may be used in future studies to develop pediatric patient dosing guidelines. A population of 48 hybrid phantoms consisting of non-uniform B-spline surfaces and polygon meshes was generated. The representative ages included the newborn, 1 year, 5 year, 10 year and 15 year male and female. For each age, the phantoms were modeled at their 10th, 50th, and 90th height percentile each at a constant 50th weight percentile. To test the impact of kidney size, the newborn phantoms were modeled with the following three kidney volumes: -15%, average, and +15%. To illustrate the impact of different morphologies on dose optimization, we calculated the effective dose for each phantom using weight-based (99m)Tc-DMSA activity administration. For a given patient weight, body habitus had a considerable effect on effective dose. Substantial variations were observed in the risk index between the 10th and 90th percentile height phantoms from the 50th percentile phantoms for a given age, with the greatest difference being 18%. There was a dependence found between kidney size and risk of radiation induced kidney cancer, with the highest risk indices observed in newborns with the smallest kidneys. Overall, the phantoms and techniques in this study can be used to provide data to refine dosing guidelines for pediatric nuclear imaging studies while taking into account the effects on both radiation dose and image quality.

AAPM/SNMMI Joint Task Force: report on the current state of nuclear medicine physics training.

The American Association of Physicists in Medicine (AAPM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) recognized the need for a review of the current state of nuclear  medicine physics training and the need to explore pathways for improving nuclear medicine physics training opportunities. For these reasons, the two organizations formed a joint AAPM/SNMMI Ad Hoc Task Force on Nuclear Medicine Physics  Training. The mission of this task force was to assemble a representative group of stakeholders to:• Estimate the demand for board-certified nuclear medicine physicists in the next 5-10 years,• Identify the critical issues related to supplying an adequate number of physicists who have received the appropriate level of training in nuclear medicine physics, and• Identify approaches that may be considered to facilitate the training of nuclear medicine physicists.As a result, a task force was appointed and chaired by an active member of both organizations that included representation from the AAPM, SNMMI, the American Board of Radiology (ABR), the American Board of Science in Nuclear Medicine (ABSNM), and the Commission for the Accreditation of Medical Physics Educational Programs (CAMPEP). The Task Force first met at the AAPM Annual Meeting in Charlotte in July 2012 and has met regularly face-to-face, online, and by conference calls. This manuscript reports the findings of the Task Force, as well as recommendations to achieve the stated mission.

Standardization of administered activities in pediatric nuclear medicine: a report of the first nuclear medicine global initiative project, part 1-statement of the issue and a review of available resources.

The Nuclear Medicine Global Initiative (NMGI) was formed in 2012 and consists of 13 international organizations with direct involvement in nuclear medicine. The underlying objectives of the NMGI were to promote human health by advancing the field of nuclear medicine and molecular imaging, encourage global collaboration in education, and harmonize procedure guidelines and other policies that ultimately lead to improvements in quality and safety in the field throughout the world. For its first project, the NMGI decided to consider the issues involved in the standardization of administered activities in pediatric nuclear medicine. This article presents part 1 of the final report of this initial project of the NMGI. It provides a review of the value of pediatric nuclear medicine, the current understanding of the carcinogenic risk of radiation as it pertains to the administration of radiopharmaceuticals in children, and the application of dosimetric models in children. A listing of pertinent educational and reference resources available in print and online is also provided. The forthcoming part 2 report will discuss current standards for administered activities in children and adolescents that have been developed by various organizations and an evaluation of the current practice of pediatric nuclear medicine specifically with regard to administered activities as determined by an international survey of nuclear medicine clinics and centers. Lastly, the part 2 report will recommend a path forward toward global standardization of the administration of radiopharmaceuticals in children.

Radiation doses for pediatric nuclear medicine studies: comparing the North American consensus guidelines and the pediatric dosage card of the European Association of Nuclear Medicine.

BACKGROUND: Estimated radiation dose is important for assessing and communicating the risks and benefits of pediatric nuclear medicine studies. Radiation dose depends on the radiopharmaceutical, the administered activity, and patient factors such as age and size. Most radiation dose estimates for pediatric nuclear medicine have not been based on administered activities of radiopharmaceuticals recommended by established practice guidelines. The dosage card of the European Association of Nuclear Medicine (EANM) and the North American consensus guidelines each provide recommendations of administered activities of radiopharmaceuticals in children, but there are substantial differences between these two guidelines. OBJECTIVE: For 12 commonly performed pediatric nuclear medicine studies, two established pediatric radiopharmaceutical administration guidelines were used to calculate updated radiation dose estimates and to compare the radiation exposure resulting from the recommendations of each of the guidelines. MATERIALS AND METHODS: Estimated radiation doses were calculated for 12 common procedures in pediatric nuclear medicine using administered activities recommended by the dosage card of the EANM (version 1.5.2008) and the 2010 North American consensus guidelines for radiopharmaceutical administered activities in pediatrics. Based on standard models and nominal age-based weights, radiation dose was estimated for typical patients at ages 1, 5, 10 and 15 years and adult. The resulting effective doses were compared, with differences greater than 20% considered significant. RESULTS: Following either the EANM dosage card or the 2010 North American guidelines, the highest effective doses occur with radiopharmaceuticals labeled with fluorine-18 and iodine-123. In 24% of cases, following the North American consensus guidelines would result in a substantially higher radiation dose. The guidelines of the EANM dosage card would lead to a substantially higher radiation dose in 39% of all cases, and in 62% of cases in which patients were age 5 years or younger. CONCLUSION: For 12 commonly performed pediatric nuclear medicine studies, updated radiation dose estimates can guide efforts to reduce radiation exposure and provide current information for discussing radiation exposure and risk with referring physicians, patients and families. There can be substantial differences in radiation exposure for the same procedure, depending upon which of these two guidelines is followed. This discordance identifies opportunities for harmonization of the guidelines, which may lead to further reduction in nuclear medicine radiation doses in children.

Pediatric nuclear medicine and radiation dose.

Nuclear medicine is a unique and valuable method that contributes to the diagnosis and assessment of many diseases in children. Radiation exposures in children undergoing diagnostic nuclear medicine studies are low. Although in the past there has been a rather large variation of pediatric radiopharmaceutical administered activities, adhering to recent standards for pediatric radiopharmaceutical administered doses can help assure that the lowest administered activity are employed and that the diagnostic value of the studies is preserved. Radiation exposures in children can be reduced further by optimizing routine protocols, application of advanced image processing and potentially with the use of advanced imaging systems.

Biological characterization of F-18-labeled rhodamine B, a potential positron emission tomography perfusion tracer.

INTRODUCTION: Myocardial infarction is the leading cause of death in western countries, and positron emission tomography (PET) plays an increasing role in the diagnosis and treatment planning for this disease. However, the absence of an (18)F-labeled PET myocardial perfusion tracer hampers the widespread use of PET in myocardial perfusion imaging (MPI). We recently reported a potential MPI agent based on (18)F-labeled rhodamine B. The goal of this study was to more completely define the biological properties of (18)F-labeled rhodamine B with respect to uptake and localization in an animal model of myocardial infarction and to evaluate the uptake (18)F-labeled rhodamine B by cardiomyocytes. METHODS: A total of 12 female Sprague Dawley rats with a permanent ligation of the left anterior descending artery (LAD) were studied with small-animal PET. The animals were injected with 100-150 µCi of (18)F-labeled rhodamine B diethylene glycol ester ([(18)F]RhoBDEGF) and imaged two days before ligation. The animals were imaged again two to ten days post-ligation. After the post-surgery scans, the animals were euthanized and the hearts were sectioned into 1mm slices and myocardial infarct size was determined by phosphorimaging and 2,3,5-triphenyltetrazolium chloride staining (TTC). In addition, the uptake of [(18)F]RhoBDEGF in isolated rat neonatal cardiomyocytes was determined by fluorescence microscopy. RESULTS: Small-animal PET showed intense and uniform uptake of [(18)F]RhoBDEGF throughout the myocardium in healthy rats. After LAD ligation, well defined perfusion defects were observed in the PET images. The defect size was highly correlated with the infarct size as determined ex vivo by phosphorimaging and TTC staining. In vitro, [(18)F]RhoBDEGF was rapidly internalized into rat cardiomyocytes with ~40 % of the initial activity internalized within the 60 min incubation time. Fluorescence microscopy clearly demonstrated localization of [(18)F]RhoBDEGF in the mitochondria of rat cardiomyocytes. CONCLUSION: Fluorine-18-labeled rhodamine B diethylene glycol ester ([(18)F]RhoBDEGF) provides excellent image quality and clear delineation of myocardial infarcts in a rat infarct model. In vitro studies demonstrate localization of the tracer in the mitochondria of cardiac myocytes. In combination, these results support the continued evaluation of this tracer for the PET assessment of myocardial perfusion.

Radiation exposure to family caregivers and nurses of pediatric neuroblastoma patients receiving 131I-metaiodobenzylguanidine (131I-MIBG) therapy.

PURPOSE: (131)I-MIBG provides molecularly targeted radiotherapy for pediatric neuroblastoma patients with relapsed or refractory disease. At our institution, designated family caregivers and nurses participate in the care of the child during hospital isolation for approximately 3-5 days post-administration. The purpose of this study was to measure radiation exposure to family caregivers and nurses caring for children with neuroblastoma during their stay in the hospital for (131)I-MIBG therapy. METHODS: Iodine-(131)I-MIBG therapy was administered to 14 children (mean age 6.7 ± 3.8 years, range 3-13 years) for relapsed or refractory neuroblastoma from 2009 to 2010. The administered activity ranged from 5.92 to 23.31 GBq (mean 13.65 ± 5.22 GBq). The mean administered activities were 8.77 ± 2.07 GBq (range 5.92-11.1 GBq) and 17.32 ± 3.4 GBq (range 11.84-23.31 GBq) for children less than 7 and 7 years or older, respectively. One or two designated caregivers received specific radiation safety training prior to treatment. One caregiver was allowed to stay in a room adjacent to the child to provide general patient care as instructed by nursing. Nurses assigned to the care of the patient also received specific radiation instructions. The total caregiver and nursing whole body radiation dose was determined using real-time personal dosimetry. RESULTS: There was no correlation between caregiver (r = -0.068, P = 0.817) or nursing (r = -0.031, P = 0.916) whole-body radiation dose and the patient-administered activity. The overall mean caregiver radiation dose was 1.79 ± 1.04 mSv, but the range of caregiver radiation doses varied by more than an order of magnitude (0.35-3.81 mSv), with no caregiver receiving more than 4.0 mSv. The overall mean nursing radiation dose was 0.44 ± 0.27 mSv per treatment, ranging from 0.15 to 1.08 mSv, with no nurse receiving more than 1.1 mSv. When grouped by patient age, there was no significant difference (P = 0.673) in the mean caregiver exposure for children less than 7 years, 1.94 ± 1.17 mSv (n = 6, range 0.7-3.81 mSv), compared to 1.69 ± 0.99 mSv (n = 8, range 0.35-3.37 mSv) for children 7 years or older. Similarly, there was no significant difference (P = 0.511) in mean nursing exposure for children less than 7 years, 0.5 ± 0.31 mSv (n = 6, range 0.18-1.08 mSv), compared to 0.4 ± 0.24 mSv (n = 8, range 0.15-0.94 mSv) for children 7 years or older. CONCLUSION: There was no significant correlation between caregiver or nursing radiation exposure and patient-administered activity or no significant difference between patient age. This may suggest that older children who tend to receive higher administered activities may require less direct caregiver support during their hospital stay. Most importantly, all caregivers and nurses received radiation doses allowed under current regulations for individuals exposed to therapy patients during hospital isolation (<5.0 mSv), although this does not include exposure the caregivers may receive once the patient leaves the hospital.

Exploratory evaluation of MR permeability with 18F-FDG PET mapping in pediatric brain tumors: a report from the Pediatric Brain Tumor Consortium.

UNLABELLED: The purpose of this study was to develop a method of registering (18)F-FDG PET with MR permeability images for investigating the correlation of (18)F-FDG uptake, permeability, and cerebral blood volume (CBV) in children with pediatric brain tumors and their relationship with outcome. METHODS: Twenty-four children with brain tumors in a phase II study of bevacizumab and irinotecan underwent brain MR and (18)F-FDG PET within 2 wk. Tumor types included supratentorial high-grade astrocytoma (n = 7), low-grade glioma (n = 9), brain stem glioma (n = 4), medulloblastoma (n = 2), and ependymoma (n = 2). There were 33 cases (pretreatment only [n = 12], posttreatment only [n = 3], and both pretreatment [n = 9] and posttreatment [n = 9]). (18)F-FDG PET images were registered to MR images from the last time point of the T1 perfusion time series using mutual information. Three-dimensional regions of interest (ROIs) drawn on permeability images were automatically transferred to registered PET images. The quality of ROI registration was graded (1, excellent; 2, very good; 3, good; 4, fair; and 5, poor) by 3 independent experts. Spearman rank correlations were used to assess correlation of maximum tumor permeability (Kps(max)), maximum CBV (CBV(max)), and maximum (18)F-FDG uptake normalized to white matter (T/W(max)). Cox proportional hazards models were used to investigate associations of these parameters with progression-free survival (PFS). RESULTS: The quality of ROI registration between PET and MR was good to excellent in 31 of 33 cases. There was no correlation of baseline Kps(max) with CBV(max) (Spearman rank correlation = 0.018 [P = 0.94]) or T/W(max) (Spearman rank correlation = 0.07 [P = 0.76]). Baseline CBV(max) was correlated with T/W(max) (Spearman rank correlation = 0.47 [P = 0.036]). Baseline Kps(max), CBV(max), and T/W(max) were not significantly associated with PFS (P = 0.42, hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.90-1.045, and number of events [n(events)] = 15 for Kps(max); P = 0.41, HR = 0.989, 95% CI = 0.963-1.015, and n(events) = 14 for CBV(max); and P = 0.17, HR = 1.49, 95% CI = 0.856-2.378, and n(events) = 15 for T/W(max)). CONCLUSION: (18)F-FDG PET and MR permeability images were successfully registered and compared across a spectrum of pediatric brain tumors. The lack of correlation between metabolism and permeability may be expected because these parameters characterize different molecular processes. The correlation of CBV and tumor metabolism may be related to an association with tumor grade. More patients are needed for a covariate analysis of these parameters and PFS by tumor histology.

Minimizing and communicating radiation risk in pediatric nuclear medicine.

The value of pediatric nuclear medicine is well established. Pediatric patients are referred to nuclear medicine from nearly all pediatric specialties including urology, oncology, cardiology, gastroenterology, and orthopedics. Radiation exposure is associated with a potential, small, risk of inducing cancer in the patient later in life and is higher in younger patients. Recently, there has been enhanced interest in exposure to radiation from medical imaging. Thus, it is incumbent on practitioners of pediatric nuclear medicine to have an understanding of dosimetry and radiation risk to communicate effectively with their patients and their families. This article reviews radiation dosimetry for radiopharmaceuticals and also CT given the recent proliferation of PET/CT and SPECT/CT. It also describes the scientific basis for radiation risk estimation in the context of pediatric nuclear medicine. Approaches for effective communication of risk to patients' families are discussed. Lastly, radiation dose reduction in pediatric nuclear medicine is explicated.