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Appropriate use criteria (AUC) are statements that contain indications describing when and how often an intervention should be performed under the optimal combination of scientific evidence, clinical judgment, and patient values while avoiding unnecessary provisions of services. Society of Nuclear

Purpose 99m Tc-MDP single-photon emission computed tomography (SPECT) is an established tool for diagnosing lumbar stress, a common cause of low back pain (LBP) in pediatric patients. However, detection of small stress lesions is complicated by the low quality of SPECT, leading to significant interreader variability. The study objectives were to develop an approach based on a deep convolutional neural network (CNN) for detecting lumbar lesions in 99m Tc-MDP scans and to compare its performance to that of physicians in a localization receiver operating characteristic (LROC) study. Methods Sixty-five lesion-absent (LA) 99m Tc-MDP studies performed in pediatric patients for evaluating LBP were retrospectively identified. Projections for an artificial focal lesion were acquired separately by imaging a 99m Tc capillary tube at multiple distances from the collimator. An approach was developed to automatically insert lesions into LA scans to obtain realistic lesion-present (LP) 99m Tc-MDP images while ensuring knowledge of the ground truth. A deep CNN was trained using 2.5D views extracted in LP and LA 99m Tc-MDP image sets. During testing, the CNN was applied in a sliding-window fashion to compute a 3D "heatmap" reporting the probability of a lesion being present at each lumbar location. The algorithm was evaluated using cross-validation on a 99m Tc-MDP test dataset which was also studied by five physicians in a LROC study. LP images in the test set were obtained by incorporating lesions at sites selected by a physician based on clinical likelihood of injury in this population. Results The deep learning (DL) system slightly outperformed human observers, achieving an area under the LROC curve (AUCLROC ) of 0.830 (95% confidence interval [CI]: [0.758, 0.924]) compared with 0.785 (95% CI: [0.738, 0.830]) for physicians. The AUCLROC for the DL system was higher than that of two readers (difference in AUCLROC [ΔAUCLROC ] = 0.049 and 0.053) who participated to the study and slightly lower than that of two other readers (ΔAUCLROC = -0.006 and -0.012). Another reader outperformed DL by a more substantial margin (ΔAUCLROC = -0.053). Conclusion The DL system provides comparable or superior performance than physicians in localizing small 99m Tc-MDP positive lumbar lesions.

PURPOSE In the current clinical practice, administered activity (AA) for pediatric molecular imaging is often based on the North American expert consensus guidelines or the European Association of Nuclear Medicine dosage card, both of which were developed based on the best clinical practice. These guidelines were not formulated using a rigorous evaluation of diagnostic image quality (IQ) relative to AA. In the guidelines, AA is determined by a weight-based scaling of the adult AA, along with minimum and maximum AA constraints. In this study, we use task-based IQ assessment methods to rigorously evaluate the efficacy of weight-based scaling in equalizing IQ using a population of pediatric patients of different ages and body weights. METHODS A previously developed projection image database was used. We measured task-based IQ, with respect to the detection of a renal functional defect at six different AA levels (AA relative to the AA obtained from the guidelines). IQ was assessed using an anthropomorphic model observer. Receiver-operating characteristics (ROC) analysis was applied; the area under the ROC curve (AUC) served as a figure-of-merit for task performance. In addition, we investigated patient girth (circumference) as a potential improved predictor of the IQ. RESULTS The data demonstrate a monotonic and modestly saturating increase in AUC with increasing AA, indicating that defect detectability was limited by quantum noise and the effects of object variability were modest over the range of AA levels studied. The AA for a given value of the AUC increased with increasing age. The AUC vs AA plots for all the patient ages indicate that, for the current guidelines, the newborn and 10- and 15-yr phantoms had similar IQ for the same AA suggested by the North American expert consensus guidelines, but the 5- and 1-yr phantoms had lower IQ. The results also showed that girth has a stronger correlation with the needed AA to provide a constant AUC for 99m Tc-DMSA renal SPECT. CONCLUSIONS The results suggest that (a) weight-based scaling is not sufficient to equalize task-based IQ for patients of different weights in pediatric 99m Tc-DMSA renal SPECT; and (b) patient girth should be considered instead of weight in developing new administration guidelines for pediatric patients.

More than one third of children with epilepsy have medically intractable seizures. Promising therapies, including targeted neurostimulation and surgery, depend on accurate localization of the epileptogenic zone. Ictal perfusion single-photon emission computed tomography (SPECT) can localize the seizure focus noninvasively, with comparable accuracy to that of invasive EEG. However, multiple factors including seizure dynamics may affect its spatial specificity. Methods : Using subtracted ictal from interictal SPECT and scalp EEG from 118 pediatric epilepsy patients (40 of whom had surgery after the SPECT studies), information theoretic measures of association and advanced statistical models, this study investigated the impact of preictal and ictal brain network dynamics on SPECT focality. Results : Network dynamics significantly impacted the SPECT localization $\sim$ 30 s before to $\sim$ 45 s following ictal onset. Distributed early ictal connectivity changes, indicative of a rapidly evolving seizure, were negatively associated with SPECT focality. Spatially localized connectivity changes later in the seizure, indicating slower seizure propagation, were positively associated with SPECT focality. In the first $\sim$ 60 s of the seizure, significantly higher network connectivity was estimated in an area overlapping with the area of hyperperfusion. Finally, $\sim$ 75% of patients with Engel class 1a/1b outcomes had SPECTs that were concordant with the resected area. Conclusion : Slowly evolving seizures are more likely to be accurately imaged with SPECT, and the identified focus may overlap with brain regions where significant topological changes occur. Significance : Measures of preictal/early ictal network dynamics may help optimize the SPECT localization, leading to improved surgical and neurostimulation outcomes in refractory epilepsy.

Abstract 99mTc-DMSA is one of the most commonly used pediatric nuclear medicine imaging agents. Nevertheless, there are no pharmacokinetic (PK) models for 99mTc-DMSA in children, and currently available pediatric dose estimates for 99mTc-DMSA use pediatric S values with PK data derived from adults. Furthermore, the adult PK data were collected in the mid-70’s using quantification techniques and instrumentation available at the time. Using pediatric imaging data for DMSA, we have obtained kinetic parameters for DMSA that differ from those applicable to adults. Methods We obtained patient data from a retrospective re-evaluation of clinically collected pediatric SPECT images of 99mTc-DMSA in 54 pediatric patients from Boston’s Children Hospital (BCH), ranging in age from 1 to 16 years old. These were supplemented by prospective data from twenty-three pediatric patients (age range: 4 months to 6 years old). Results In pediatric patients, the plateau phase in fractional kidney uptake occurs at a fractional uptake value closer to 0.3 than the value of 0.5 reported by the International Commission on Radiological Protection (ICRP) for adult patients. This leads to a 27% lower time-integrated activity coefficient in pediatric patients than in adults. Over the age range examined, no age dependency in uptake fraction at the clinical imaging time was observed. Female pediatric patients had a 17% higher fractional kidney uptake at the clinical imaging time than males (P < 0.001). Conclusions Pediatric 99mTc-DMSA kinetics differ from those reported for adults and should be considered in pediatric patient dosimetry. Alternatively, the differences obtained in this study could reflect improved quantification methods and the need to re-examine DMSA kinetics in adults.

OBJECTIVES Chronic acalculous cholecystitis (CAC) increasingly is being diagnosed as a cause of recurring biliary symptoms in children, but its clinical diagnosis remains challenging. The primary objective was to evaluate the utility of hepatocholescintigraphy in pediatric patients with suspected CAC. A secondary objective was to describe their clinical follow-up after diagnosis. METHODS Medical records of patients (aged 9-20 years) who underwent hepatocholescintigraphy from February 2008 to January 2012 were reviewed. Patients with gallstones, and with ≤1 year of clinical follow-up, and studies without gallbladder (GB) stimulation were excluded. GB ejection fraction (GBEF) of

No consistent guidelines exist for the acquisition of a CT scan as part of pediatric PET/CT. Given that children may be more vulnerable to the effects of ionizing radiation, it is necessary to develop methods that provide diagnostic-quality imaging when needed, in the shortest time and with the lowest patient radiation exposure. This article describes the basics of CT dosimetry and PET/CT acquisition in children. We describe the variability in pediatric PET/CT techniques, based on a survey of 19 PET/CT pediatric institutions in North America. The results of the survey demonstrated that, although most institutions used automatic tube current modulation, there remained a large variation of practice, on the order of a factor of 2–3, across sites, pointing to the need for guidelines. We introduce the approach developed at our institution for using a multiseries PET/CT acquisition technique that combines diagnostic-quality CT in the essential portion of the field of view and a low-dose technique to image the remainder of the body. This approach leads to a reduction in radiation dose to the patient while combining the PET and the diagnostic CT into a single acquisition. The standardization of pediatric PET/CT provides an opportunity for a reduction in the radiation dose to these patients while maintaining an appropriate level of diagnostic image quality.

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.

OBJECTIVE. Split renal function (SRF) can be estimated with 99mTc-labeled dimercaptosuccinic acid (DMSA) SPECT cortical renal scintigraphy on either 2D projected images or 3D images. The purpose of this study was to determine whether there is a significant difference between SRF values calculated with the 2D method and those calculated with the 3D method. MATERIALS AND METHODS. This retrospective study was performed with 99mTc-DMSA SPECT images of 316 patients (age range, 1–26 years). All images were reconstructed by filtered back projection. An automated computational method was developed to estimate SRF using both 2D projection images and direct 3D images. A paired t test was used to evaluate the difference between SRFs determined with the two methods and the association between the magnitude of the differences and kidney size, patient age, and SRF. RESULTS. There was strong correlation between SRFs estimated with the 2D and 3D methods (r = 0.94, p < 0.001). There was small significant difference (0.14%...

We sought to describe the practice of pediatric nuclear medicine at general hospitals in the United States and to assess the impact of dose awareness campaigns such as Image Gently. Methods: A web-based survey was developed that requested information regarding hospital type, whether the hospital practices pediatric nuclear medicine, and the hospital’s method for determining the administered activity for children. The survey invitation was emailed to a sample of general hospitals with more than 300 beds, excluding dedicated pediatric, veterans, psychiatric, and rehabilitation hospitals. Data were collected for 5 procedures performed on children: 99mTc-methylene diphosphate (MDP) bone scans, 99mTc-mercaptoacetyltriglycine (MAG3) renograms, 99mTc-dimercaptosuccinic acid (DMSA) renal cortical scans, 99mTc-based hepatobiliary scans, and 18F-FDG PET scans. The sites reported dosage by weight (MBq/kg), minimum and maximum dosages, and the activities that they would administer to 2 hypothetical patients: a 5-y-old boy (20 kg, 110 cm tall) and a 10-y-old girl (30 kg, 140 cm tall). Results: The invitation was delivered to 196 sites, with 121 (61.7%) responding. Eighty-two hospitals (67.8%) performed nuclear medicine on children. All sites scaled administered activity for children, mostly by body weight. Also, 82.4% of sites indicated they were familiar with Image Gently, 57.1% were familiar with the 2010 North American consensus guidelines for children, and 54.9% altered their protocols because of the guidelines. The median value for parameters defined by the guidelines was equal to the guideline-recommended value for all procedures. More than 50% of the sites—particularly those familiar with the guidelines—were compliant with the guidelines regarding both the acquisition parameters and the administered activities for the 2 hypothetical patients. However, there remained a wide variation in practice, sometimes by more than a factor of 10, for sites not familiar with the guidelines. Conclusion: Image Gently and the North American guidelines have had a substantial impact on pediatric nuclear medicine practice in the United States. However, a wide variation in practice still exists, particularly for sites not familiar with the guidelines. Further promotion and dissemination of the guidelines and best practice are still necessary.

Nuclear medicine is a unique and valuable method that contributes to the diagnosis and assessment of many diseases in children. It is generally accepted that radiation exposures to children undergoing diagnostic nuclear medicine studies and the resulting risks are low. However, due to the lack of pediatric guidelines there has been a rather wide variation of pediatric radiopharmaceutical administered activities. As a result, pediatric radiation exposures have also varied over a broad range. Some practices have been able to obtain useful results with administered activities in the lowest ranges while other centers and practices have used considerably larger administered activities. This was dramatically highlighted by surveys of nuclear medicine departments in North America and beyond. Efforts in Europe and North America have resulted in the development and publication of pediatric guidelines. These were initially developed separately utilizing different models, but more recently were joined through harmonization activities; the two sets of guidelines are now further aligned. Dissemination of these guidelines is an ongoing activity. We believe that adhering to these standards can help assure that the most appropriate administered activity is employed. Along with this goal, it is essential that the image quality and their diagnostic value be assured. Beyond the application of the recent guidelines, radiation exposures in children can be reduced further by optimizing use, updating protocols, applying advanced image processing and potentially developing and introducing advanced imaging systems. Further improvements will likely result from increased communication and cooperation by several nuclear medicine organizations in addition to the dissemination of updated information to the clinic.

The nuclear medicine procedures 99mTc-ECD SPECT and 18F-FDG PET play an important diagnostic role in children with refractory seizures. In select patients, surgical removal of epileptogenic cortex is a therapeutic option. Magnetic resonance imaging (MRI) is the principal imaging method used to identify which patients would benefit from the surgery. However, there are cases when MRI does not detect an abnormality (MRI-negative epilepsy). Under these, and other circumstances, functional nuclear medicine studies are helpful in the workup of these patients. A combination of nuclear medicine procedures with MRI and CT depicts functional–anatomic relationships and assists in the non-invasive localization of epileptogenic cortex. Information derived from these procedures is valuable in the selection of candidates for surgical resection. Timing of tracer administration in relation to imaging and monitoring the state of brain activation are essential for accurate interpretation. Ictal and interictal perfusion single photon computed tomography (SPECT), with digital subtraction and registration to MRI can define the region of ictal cortical hyperperfusion more clearly than separate image interpretation. Ictal SPECT is more sensitive than interictal positron emission computed tomography (PET) and interictal PET is more sensitive than interictal SPECT. Interictal SPECT and PET are easier to obtain than ictal SPECT, since they do not require coordination between seizure onset and tracer administration. When surface electrode grids or depth electrodes are planned, anatomic-functional images can assist in their anatomic positioning. The best results are obtained when the planning, execution and interpretation of nuclear medicine procedures are carried out with the support of a well-trained multidisciplinary team familiar with children and refractory seizures.

Nuclear medicine and molecular imaging procedures play an important role in the diagnosis, assessment, and treatment of many diseases. These include diseases of the heart, skeleton, brain, and kidneys as well as applications in oncology. The following article discusses various nuclear medicine diagnostic and therapeutic applications, and the technology behind them. Finally, radiation safety in the context of nuclear medicine will be discussed. It is important that all members of the nuclear medicine team are equipped to provide an appropriate discussion of the benefits and risks of nuclear medicine to our patients and their families.

Skeletal scintigraphy is most performed in pediatric patients using the radiopharmaceutical 99mTc labelled methylene diphosphonate (99mTc-MDP). Reference biokinetic models for 99mTc-MDP indicate 50% of the administered activity is uniformly localized to the interior bone surfaces (trabecular and cortical regions), yet imaging data clearly show some preferential uptake to the epiphyseal growth plates of the long bones. To explore the dosimetric consequences of these regional activity concentrations, we have modified mesh-type computational phantoms of the International Commission on Radiological Protection (ICRP) reference pediatric series to explicitly include geometric models of the epiphyseal growth plates (2 mm in thickness) within the left/right, distal/proximal ends of the humeri, radii, ulnae, femora, tibia, and fibulae. Bone mineral activity from the ICRP Publication 128 biokinetic model for 99mTc-MDP (ICRP 2015) was then partitioned to the growth plates at values of 0.5%, 4.4%, 8.3%, 12.2%, 16.1%, and 20%. Radiation transport simulations were performed to compute 99mTc S-values and organ dose coefficients to the soft tissues and to bone site-specific regions of spongiosa. As the percentage of bone activity assigned to the growth plates was increased (from 0.5% to 20%), absorbed doses to the soft tissue organs, active bone marrow, bone endosteum (BE), as well as the detriment-weighted dose, were shown to decrease from their nominal values (no substantial growth plate activity), while epiphyseal plate self-doses increased. In the 15 year old male phantom, moving from 0.5% to 20% relative bone activity within the epiphyseal plates resulted in a 15% reduction in active marrow (AM) and BE dose, a 10% reduction in mean soft tissue and detriment-weighted dose, and a 6.3-fold increase in epiphyseal plate self-dose. In the newborn female phantom, we observed a 18% decrease in AM and BE dose, a 10% decrease in mean soft tissue dose, a 15% decrease in detriment-weighted dose, and 12.8-fold increase in epiphyseal plate self-dose. Increases (to 3 mm) and decreases (to 1 mm) in the assumed growth plate thickness of our models were shown to impact only the growth plate self-dose. Future work in differential quantification of 99mTc-MDP activity-growth plates versus other bone surfaces-is required to provide clinically realistic data on activity partitioning as a function of patient age, and perhaps skeletal site. The phantom series presented here may be used to develop more optimized age-related guidance on 99mTc-MDP administered activities to children.

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.

The goal of this investigation was to assess the impact of the publication of the 2010 North American guidelines on the practice of nuclear medicine in children at 13 dedicated pediatric institutions within the United States and Canada by comparing results of similar surveys from 2007 and 2013. Methods: In 2013, a follow-up survey was performed of the original 13 dedicated pediatric institutions initially surveyed in 2007. Both surveys inquired about the administered activities for 16 nuclear medicine procedures commonly performed on children. The administered activity per body mass, the maximum activity, and the minimum activity for patients for each procedure were requested from each site. For each parameter the minimum and maximum reported values, as well as the median and the mean, were tabulated. The mean difference in the mean between 2007 and 2013 was calculated, as well as the 95% confidence intervals for the mean administered activity per body mass for both years. The factor of variation used with the previous survey for each parameter was calculated by taking the ratio of the maximum and minimum reported values. For the 8 procedures addressed in the 2010 North American guidelines, the percentage of institutions that were compliant (defined as within 20%) for each parameter were noted for both surveys. Institutions were asked whether they were familiar with “Image Gently,” the North American guidelines, and the “Go with the Guidelines” campaign and whether they adjusted their administered activities on the basis of these guidelines. Results: In general, the 13 pediatric institutions have reduced their administered activities in children, particularly for those procedures addressed by the 2010 North American guidelines. The average variability in the activity per body mass and the minimum activity as measured by the factor of variation were substantially reduced by 9.7% (from 3.1 to 2.8) and 24% (from 10.0 to 7.6). The average variability of the maximum activity was increased by 6.1% (from 3.3 to 3.5), but the increase was mostly due to some sites reducing their limits while others maintained their previous values. For the 8 procedures addressed by the guidelines, half or more of the institutions were compliant (within 20%) with the associated parameters in 66% of the cases. Ten of the 13 institutions reported that they adjusted their administered activities according to the North American guidelines. Conclusion: The publication of these guidelines and the associated public relations program appear to have had a positive effect with regard to both dose optimization and procedure standardization in pediatric nuclear medicine.

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. 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. 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. 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. 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.

To determine if the minimum administered radiopharmaceutical activity for hepatobiliary scintigraphy can be reduced while preserving diagnostic image quality using enhanced planar processing (EPP).A total of 40 infants between 10 and 270 days old (body mass 2.2 - 6.5 kg) had hepatobiliary scintigraphy during the period 2004 - 2010 following the intravenous administration of either (99m)Tc-mebrofenin (18 patients) or (99m)Tc-disofenin (22 patients). Due to the small size of these patients, they all received the minimum administered activity of 18.5 MBq consistent with the North American Consensus Guidelines. Six nuclear medicine physicians subjectively graded the acceptability of the image quality for clinical interpretation using a four-point scale (not acceptable, fair, good, excellent). Each physician independently graded seven image sets including the original study (full activity) and simulated reduced activity studies using binomial subsampling (50% of full activity, 25% of full activity and activity reduced by weight), with and without EPP.For full-activity studies, 98% were deemed acceptable by the six physicians for clinical interpretation. The percentages of acceptable 50% reduced activity studies with and without EPP were not significantly different from the percentage of acceptable full-activity studies (P = 0.193 and P = 0.998, respectively). The percentage of acceptable 25% reduced activity studies without EPP was significantly different from the percentage of acceptable full-activity studies (P0.001); however, this difference vanished when EPP was applied (P = 0.482). The activity reduced by weight ranged from 1.85 to 4.81 MBq (10% to 26% of full dose) and the percentages of acceptable studies with and without EPP were significantly different from the percentage of acceptable full-activity studies (P0.001 and P = 0.02, respectively).Clinically interpretable hepatobiliary scintigraphy images can be obtained in infants when the minimum administered activity is substantially reduced. Without EPP, clinically acceptable images may be produced with a reduction of 50%, and with EPP, a reduction of 75% or more may be possible.

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.

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 100–150μCi 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 60min 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.

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 (

Introduction The α v β 3 integrin, which is expressed by angiogenic epithelium and some tumor cells, is an attractive target for the development of both imaging agents and therapeutics. While optimal implementation of α v β 3 -targeted therapeutics will require a priori identification of the presence of the target, the clinical evaluation of these compounds has typically not included parallel studies with α v β 3 -targeted diagnostics. This is at least partly due to the relatively limited availability of PET radiopharmaceuticals in comparison to those labeled with 99m Tc. In an effort to begin to address this limitation, we evaluated the tumor uptake of 99m Tc-NC100692, a cyclic RGD peptide that binds to α v β 3 with ~1-nM affinity, in an α v β 3 -positive tumor model as well as its in vivo specificity. Methods MicroSPECT imaging was used to assess the ability of cilengitide, a therapeutic with high affinity for α v β 3 , to block and displace 99m Tc-NC100692 in an orthotopic U87 glioma tumor. The specificity of 99m Tc-NC100692 was quantitatively evaluated in mice bearing subcutaneous U87MG tumors, by comparison of the biodistribution of 99m Tc-NC100692 with that of the non-specific structural analogue 99m Tc-AH-111744 and by blocking uptake of 99m Tc-NC100692 with excess unlabeled NC100692. Results MicroSPECT imaging studies demonstrated that uptake of 99m Tc-NC100692 in the intracranial tumor model was both blocked and displaced by the α v β 3 -targeted therapeutic cilengitide. Biodistribution studies provided quantitative confirmation of these imaging results. Tumor uptake of 99m Tc-NC100692 at 1h post-injection was 2.8±0.7% ID/g compared to 0.38±0.1% ID/g for 99m Tc-AH-111744 ( p 99m Tc-NC100692 uptake by pre-injecting the mice with excess unlabeled NC100692 reduced tumor uptake by approximately five-fold, to 0.68±0.3% ID/g ( p =0.01). Conclusion These results confirm that 99m Tc-NC100692 does, in fact, target the α v β 3 integrin and may, therefore, be useful in identifying patients prior to anti-α v β 3 therapy as well as monitoring the response of these patients to therapy.

Ictal SPECT is promising for accurate non-invasive localization of the epileptogenic brain tissue in focal epilepsies. However, high quality ictal scans require meticulous attention to the seizure onset. In a relatively large cohort of pediatric patients, this study investigated the impact of the timing of radiotracer injection, MRI findings and seizure characteristics on ictal SPECT localizations, and the relationship between concordance of ictal SPECT, scalp EEG and resected area with seizure freedom following epilepsy surgery.Scalp EEG and ictal SPECT studies from 95 patients (48 males and 47 females, median age=11years, (25th, 75th) quartiles=(6.0, 14.75) years) with pharmacoresistant focal epilepsy and no prior epilepsy surgery were reviewed. The ictal SPECT result was examined as a function of the radiotracer injection delay, seizure duration, epilepsy etiology, cerebral lobe of seizure onset identified by EEG and MRI findings. Thirty two patients who later underwent epilepsy surgery had postoperative seizure freedom data at1, 6 and 12 months.Sixty patients (63.2%) had positive SPECT localizations - 51 with a hyperperfused region that was concordant with the cerebral lobe of seizure origin identified by EEG and 9 with discordant localizations. Of these, 35 patients (58.3%) had temporal and 25 (41.7%) had extratemporal seizures. The ictal SPECT result was significantly correlated with the injection delay (p0.01) and cerebral lobe of seizure onset (specifically frontal versus temporal; p=0.02) but not MRI findings (p=0.33), epilepsy etiology (p≥0.27) or seizure duration (p=0.20). Concordance of SPECT, scalp EEG and resected area was significantly correlated with seizure freedom at 6 months after surgery (p=0.04).Ictal SPECT holds promise as a powerful source imaging tool for presurgical planning in pediatric epilepsies. To optimize the SPECT result the radiotracer injection delay should be minimized to≤25s, although the origin of seizure onset (specifically temporal versus frontal) also significantly impacts the localization.

Although uncommon, musculoskeletal malignancies are major contributors to morbidity and mortality in children and young adults. (18)F-Fluorodeoxyglucose (FDG)-PET can play an important role in disease management, including staging, assessing response to therapy, and evaluating for recurrence. Advantages of (18)F-FDG-PET and (18)F-FDG-PET/computed tomography (CT) include the capability to assess tumor activity and a large field of view that can include the whole body or torso. (18)F-FDG-PET does not always discriminate benign and malignant musculoskeletal lesion, but it can serve to guide diagnostic procedures, such as needle biopsy. In patients with osteosarcoma, FDG-PET/CT cannot replace a 99mTc-methyldiphosphonate bone scan for localization of skeletal metastases. FDG-PET may be useful for the evaluation of non-rhabdomyosarcoma sarcomas on a case-by-case basis. (18)F-FDG-PET or PET/CT is most useful for identifying sites of distant disease in patients with newly diagnosed or recurrent Ewing sarcoma, rhabdomyosarcoma, or osseous lymphoma.

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.

Background Absorbed dose estimates for pediatric patients require pharmacokinetics that are, to the extent possible, age-specific. Such age-specific pharmacokinetic data are lacking for many of the diagnostic agents typically used in pediatric imaging. We have developed a pharmacokinetic model of [18F]fluorodeoxyglucose (FDG) applicable to premature infants and to 0- (newborns) to 5-year-old patients, which may be used to generate model-derived time-integrated activity coefficients and absorbed dose calculations for these patients. Methods The FDG compartmental model developed by Hays and Segall for adults was fitted to published data from infants and also to a retrospective data set collected at the Boston Children’s Hospital (BCH). The BCH data set was also used to examine the relationship between uptake of FDG in different organs and patient weight or age. Results Substantial changes in the structure of the FDG model were required to fit the pediatric data. Fitted rate constants and fractional blood volumes were reduced relative to the adult values. Conclusions The pharmacokinetic models developed differ substantially from adult pharmacokinetic (PK) models which can have considerable impact on the dosimetric models for pediatric patients. This approach may be used as a model for estimating dosimetry in children from other radiopharmaceuticals. Electronic supplementary material The online version of this article (doi:10.1186/s13550-016-0179-6) contains supplementary material, which is available to authorized users.

We recently reported the development of the 2-[(18)F]fluoroethyl ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging. This compound, which was prepared using a [(18)F]fluoroethyl prosthetic group, has significant uptake in the myocardium in rats but also demonstrates relatively high liver uptake and is rapidly hydrolyzed in vivo in mice. We have now prepared (18)F-labeled rhodamine B using three additional prosthetic groups (propyl, diethylene glycol, and triethylene glycol) and found that the prosthetic group has a significant effect on the in vitro and in vivo properties of these compounds. Of the esters prepared to date, the diethylene glycol ester is superior in terms of in vitro stability and pharmacokinetics. These observations suggest that the prosthetic group plays a significant role in determining the pharmacological properties of (18)F-labeled compounds. They also support the value of continued investigation of (18)F-labeled rhodamines as PET radiopharmaceuticals for myocardial perfusion imaging.

In the chest, the indications for nuclear medicine studies are broader and more varied in children than in adults. In children, nuclear medicine studies are used to evaluate congenital and developmental disorders of the chest, as well as diseases more typical of adults. In the chest, pediatric nuclear medicine uses the same radiopharmaceuticals and imaging techniques as used in adults to evaluate cardiac and pulmonary disease, aerodigestive disorders, and pediatric malignancies. The introduction of PET (mostly using (18)F-FDG) has transformed pediatric nuclear oncology, particular for imaging malignancies in the chest.

Background. The traditional initial imaging approach following pediatric urinary tract infection is the “bottom-up” approach (cystogram and renal ultrasound). Recently, the “top-down” approach (nuclear renal scan followed by cystogram for abnormal scans only) has gained increasing attention. The relative cost and radiation doses of these are unknown Methods. The authors used a decision model to evaluate these imaging approaches. Cost and effective radiation dose estimates, including sensitivity analyses, were based on one-time imaging only. Results. Comparing hypothetical cohorts of 100 000 children, the top-down imaging approach cost $82.9 million versus $59.2 million for the bottom-up approach. Per-capita effective radiation dose was 0.72 mSv for top-down compared with 0.06 mSv for bottom-up. Conclusions. Routine use of nuclear renal scans in children following initial urinary tract infection diagnosis would result in increased imaging costs and radiation doses as compared to initial cystogram and ultrasound. Further data are required to clarify the long-term clinical implications of this increase.

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.

Nuclear medicine has an important role in the care of newborns and children less than 1 y old. Patients in this age group present with a spectrum of diseases different from those of older children or adults. These patients can benefit from the full range of nuclear medicine studies. In these young children, nuclear medicine studies are more likely to be used to evaluate a wide range of congenital conditions but also can be helpful for evaluating acquired conditions such as infection, cancer, and trauma. This review first will cover the general aspects of nuclear medicine practice with these patients, including the special considerations that can help achieve successful diagnostic imaging. These topics will include clinical indications, imaging technology, instrumentation, software, positioning and immobilization, sedation, local and general anesthesia, radiopharmaceutical doses, radiation risk, and dose reduction. The review then will discuss the specific nuclear medicine studies that typically are obtained in patients in this age group. With extra care and attention to the special needs of this population, nuclear medicine departments can successfully study patients less than 1 y old.

Molecular imaging with positron emission tomography (PET) plays an important role in the diagnosis and management of patients with brain tumors and epilepsy. The clinical uses of FDG are discussed, as well as the research applications of novel PET tracers. Where applicable, single-photon emission computed tomography (SPECT) is also discussed.

The purpose of this study was to assess 18F-FDG uptake in children with a newly diagnosed diffuse intrinsic brain stem glioma (BSG) and to investigate associations with progression-free survival (PFS), overall survival (OS), and MRI indices. Methods: Two Pediatric Brain Tumor Consortium (PBTC) therapeutic trials in children with newly diagnosed BSG were designed to test radiation therapy combined with molecularly targeted agents (PBTC-007: phase I/II study of gefitinib; PBTC-014: phase I/II study of tipifarnib). Baseline brain 18F-FDG PET scans were obtained in 40 children in these trials. Images were evaluated by consensus between 2 PET experts for intensity and uniformity of tracer uptake. Associations of 18F-FDG uptake intensity and uniformity with both PFS and OS, as well as associations with tumor MRI indices at baseline (tumor volume on fluid-attenuated inversion recovery, baseline intratumoral enhancement, diffusion and perfusion values), were evaluated. Results: In most of the children, BSG 18F-FDG uptake was less than gray-matter uptake. Survival was poor, irrespective of intensity of 18F-FDG uptake, with no association between intensity of 18F-FDG uptake and PFS or OS. However, hyperintense 18F-FDG uptake in the tumor, compared with gray matter, suggested poorer survival rates. Patients with 18F-FDG uptake in 50% or more of the tumor had shorter PFS and OS than did patients with 18F-FDG uptake in less than 50% of the tumor. There was some evidence that tumors with higher 18F-FDG uptake were more likely to show enhancement, and when the diffusion ratio was lower, the uniformity of 18F-FDG uptake appeared higher. Conclusion: Children with BSG for which 18F-FDG uptake involves at least half the tumor appear to have poorer survival than children with uptake in less than 50% of the tumor. A larger independent study is needed to verify this hypothesis. Intense tracer uptake in the tumors, compared with gray matter, suggests decreased survival. Higher 18F-FDG uptake within the tumor was associated with enhancement on MR images. Increased tumor cellularity as reflected by restricted MRI diffusion may be associated with increased 18F-FDG uniformity throughout the tumor.

To perform a preliminary evaluation of the image quality of pediatric technetium 99m ((99m)Tc) methylene diphosphonate (MDP) bone single photon emission computed tomography (SPECT) by using iterative reconstruction-ordered subset expectation maximization with three-dimensional resolution recovery (OSEM-3D)-and to assess whether any improvements with use of this technique could lead to a reduction in patient dose or a shortening in imaging time.Institutional advisory board approval was obtained for this investigation. Fifty (99m)Tc-MDP SPECT studies of the spine were evaluated (36 female and 14 male patients; mean age, 15.5 years). Each study was acquired by using a dual-detector camera, with each detector rotating 360°. By using filtered back projection (FBP) and OSEM-3D, images were reconstructed from data generated by both detectors. Likewise, OSEM-3D was used to reconstruct data from a single detector simulating half the administered radiopharmaceutical activity. Two nuclear medicine physicians, blinded to the patient data, reviewed the images for image quality in four different categories by using a four-point scale: artifacts (category 1), lesions (category 2), noise (category 3), and image sharpness (category 4).Compared with FBP, images reconstructed by using OSEM-3D with one or two detectors showed significant improvement in image quality with regard to lesion detection, noise level, and image sharpness (P.02, .01, and .001, respectively). With OSEM-3D, no significant differences were observed when either one or two detectors were used.Improved image quality of skeletal SPECT with either a 50% reduction in radiation dose or a 50% reduction in acquisition time or combination of the two can be achieved by using OSEM-3D.

OBJECTIVE. Athletes can have pain derived from fractures or alternate pathology. Skeletal scintigraphy may detect abnormalities before anatomic imaging and provides a practical tool for whole-body imaging. However, study interpretation in children can be challenging. This pictorial essay describes a technique for pediatric skeletal scintigraphy and reviews findings commonly encountered in athletes.CONCLUSION. Skeletal scintigraphy complements anatomic findings in pediatric athletes. Familiarity with imaging technique and study interpretation can improve diagnosis.

Background: The primary function of integrin β7 is the recruitment and retention of lymphocytes to the inflamed gut. The aim of this study was to investigate the possibility of imaging colitis radioimmunodetection by targeting the β7 integrin with a radiolabeled antibody. Methods: FIB504.64, a monoclonal antibody that binds to β7 integrin, was conjugated with a bifunctional chelator and labeled with 64Cu. The antibody (50 μg, 7 MBq) was injected into C57BL/6 mice with experimentally induced colitis (n = 6). MicroPET images were collected at 1, 24, and 48 hours postinjection and the biodistribution was measured at 48 hours by tissue assay. Data were also obtained for a 64Cu-labeled nonspecific isotype-matched antibody in mice with colitis and 64Cu-labeled FIB504.64 in healthy mice (n = 5–6). Results: The microPET images showed higher uptake of 64Cu-labeled FIB504.64 in the gut of mice with colitis than for either of the controls. This observation was confirmed by the 48-hour ex vivo biodistribution data: the percentage of injected dose per gram of tissue (%ID/g ± SD) (large intestine) colitis mice with 64Cu-labeled FIB504.64, 6.49 ± 2.25; control mice with 64Cu-labeled FIB504.64, 3.64 ± 1.12; colitis mice, 64Cu-labeled nonspecific antibody 3.97 ± 0.48%ID/g (P < 0.05 between groups). Conclusions: The selective uptake of 64Cu-labeled FIB504.64 antibody in the gut of animals with colitis suggests that integrin β7 may be a promising target for radioimmunodetection of this disease, which would aid diagnosis, assessment, and therapy guidance of this disease. Inflamm Bowel Dis 2010

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.

Fluorine-18-labeled rhodamine B was developed as a potential positron emission tomography (PET) tracer for the evaluation of myocardial perfusion, but preliminary studies in mice showed no accumulation in the heart suggesting that it was rapidly hydrolyzed in vivo in mice. A study was therefore undertaken to further evaluate this hypothesis.[(18)F]Fluoroethylrhodamine B was equilibrated for 2 h at 37 degrees C in human, rat and mouse serum and in phosphate-buffered saline. Samples were removed periodically and assayed by high-performance liquid chromatography. Based on the results of the stability study, microPET imaging and a biodistribution study were carried out in rats.In vitro stability studies demonstrated that [(18)F]fluoroethylrhodamine B much more stable in rat and human sera than in mouse serum. After 2 h, the compound was80% intact in rat serum but30% intact in mouse serum. The microPET imaging and biodistribution studies in rats confirmed this result showing high and persistent tracer accumulation in the myocardium compared with the absence of uptake by the myocardium in mice thereby validating our original hypothesis that (18)F-labeled rhodamines should accumulate in the heart.[(18)F]Fluoroethylrhodamine B is more stable in rat and human sera than it is in mouse serum. This improved stability is demonstrated by the high uptake of the tracer in the rat heart in comparison to the absence of visible uptake in the mouse heart. These observations suggest that (18)F-labeled rhodamines are promising candidates for more extensive evaluation as PET tracers for the evaluation of myocardial perfusion.

To compare two methods of reconstructing technetium 99m (99mTc) dimercaptosuccinic acid (DMSA) renal single photon emission computed tomographic (SPECT) data--ordered subset expectation maximization with three-dimensional resolution recovery (OSEM-3D) and filtered back projection (FBP)--in children in terms of improving image quality and reducing the radiopharmaceutical activity and radiation dose.The institutional review board approved this retrospective study and waived the requirement for informed patient consent. Fifty sequential pediatric patient 99mTc-DMSA SPECT studies of 98 kidneys were retrospectively analyzed by using a dual-detector gamma camera. FBP reconstruction with data from both detectors was compared with OSEM-3D reconstruction with half the gamma photon counts (ie, data from only one detector). Two nuclear medicine physicians blinded to the patients' medical histories and reconstruction techniques evaluated the studies. Scores for image quality, renal size, and relative function were compared by using paired t tests. Total scores for renal cortical defects were compared by using the Wilcoxon signed rank test. The kappa coefficient was calculated as an indicator of the concordance between the OSEM-3D and FBP reconstruction methods.Image quality was significantly enhanced with OSEM-3D (P.001, paired t test). Cortical defects were identified better on OSEM-3D images than on FBP images. Of the 98 kidney SPECT studies analyzed, 19 showed identical cortical defects and 75 showed none at both OSEM-3D and FBP. In four kidneys, OSEM-3D depicted cortical defects that were not seen with FBP. No significant difference in relative renal function between the two methods was observed (P = .973).Compared with FBP, OSEM-3D yielded superior image quality in the evaluation of 99mTc-DMSA renal SPECT data, with the potential for markedly reduced radiation doses and/or shorter scanning times for patients.

Universally applied standards for administering radiopharmaceutical doses in children do not presently exist. Hence, pediatric radiopharmaceutical dosimetry varies considerably from institution to institution and is generally based on the recommended adult dose adjusted for body mass. Methods: We surveyed 13 pediatric hospitals in North America to obtain objective data on dosimetry practices for 16 pediatric nuclear medicine examinations, including the minimum total radiopharmaceutical administered dose per examination, the total administered dose based on body mass, and maximum total doses in children. Results: The reported administered doses of radiopharmaceuticals to children vary over a relatively large range, especially with respect to minimum total administered doses. Conclusion: This survey has identified a broad range of administered doses directly leading to variability in radiation-absorbed doses to patients. The nuclear medicine community should develop pediatric standards for radiopharmaceutical administered doses and reduce radiation exposure in children, such as through the use of modern software reconstruction techniques.

Although (18)F-labeled NaF was the first widely used agent for skeletal scintigraphy, it quickly fell into disuse after the introduction of (99m)Tc-labeled bone-imaging agents. Recent comparative studies have demonstrated that (18)F-fluoride PET is more accurate than (99m)Tc-diphosphonate SPECT for identifying both malignant and benign lesions of the skeleton. Combining (18)F-fluoride PET with other imaging, such as CT, can improve the specificity and overall accuracy of skeletal (18)F-fluoride PET and probably will become the routine clinical practice for (18)F-fluoride PET. Although (18)F-labeled NaF and (99m)Tc-diphosphonate have a similar patient dosimetry, (18)F-fluoride PET offers shorter study times (typically less than 1 h), resulting in a more efficient workflow, improved patient convenience, and faster turnarounds of reports to the referring physicians. With the widespread availability of PET scanners and the improved logistics for the delivery of (18)F radiopharmaceuticals, prior limitations to the routine use of (18)F-fluoride bone imaging have largely been overcome. The favorable imaging performance and the clinical utility of (18)F-fluoride PET, compared with (99m)Tc-diphosphonate scintigraphy, support the reconsideration of (18)F-fluoride as a routine bone-imaging agent.

The advancement of positron emission tomography (PET) depends on the development of new radiotracers that will complement 18 F-FDG. Copper-64 ( 64 Cu) is a promising PET radionuclide, particularly for antibody-targeted imaging, but the high in vivo lability of conventional chelates has limited its clinical application. The objective of this work was to evaluate the novel chelating agent SarAr (1- N -(4-aminobenzyl)-3, 6,10,13,16,19-hexaazabicyclo[6.6.6] eicosane-1,8-diamine) for use in developing a new class of tumor-specific 64 Cu radiopharmaceuticals for imaging neuroblastoma and melanoma. The anti-GD2 monoclonal antibody (mAb) 14.G2a, and its chimeric derivative, ch14.18, target disialogangliosides that are overexpressed on neuroblastoma and melanoma. Both mAbs were conjugated to SarAr using carbodiimide coupling. Radiolabeling with 64 Cu resulted in >95% of the 64 Cu being chelated by the immunoconjugate. Specific activities of at least 10 μCi/μg (1 Ci = 37 GBq) were routinely achieved, and no additional purification was required after 64 Cu labeling. Solid-phase radioimmunoassays and intact cell-binding assays confirmed retention of bioactivity. Biodistribution studies in athymic nude mice bearing s.c. neuroblastoma (IMR-6, NMB-7) and melanoma (M21) xenografts showed that 15–20% of the injected dose per gram accumulated in the tumor at 24 hours after injection, and only 5–10% of the injected dose accumulated in the liver, a lower value than typically seen with other chelators. Uptake by a GD2-negative tumor xenograft was significantly lower (64 Cu-SarAr-mAb system described here is potentially applicable to 64 Cu-PET imaging with a broad range of antibody or peptide-based imaging agents.

Children generally are at greater risk from radiation exposure due to their greater sensitivity to radiation and the longer time frame after exposure during which effects can manifest themselves. Thus, reducing radiation exposure is a major concern in pediatric nuclear medicine imaging. Lower administered activities (AA) can reduce patient radiation exposure, but also result in reduced diagnostic accuracy. Typically, the administered activity for diagnostic nuclear medicine imaging of children is based on patient weight, but our previous studies have shown that weight alone may not be sufficient to accurately determine an optimal patient-specific AA. The ultimate goal of this work is to investigate the tradeoff between image quality and radiation risk as a function of AA, patient age, gender and body habitus that can be used to guide dosing of dimercaptosuccinic acid (DMSA) SPECT, a common pediatric nuclear medicine procedure for assessing renal function. In this work we created a model of kidney function defects and used it to generate defects for a population of anthropomorphic reference phantoms with realistic age-dependent variations in anatomy and pharmacokinetic model based organ uptakes. The population includes 90 phantoms modeling both genders, variations in height and weight, and ages from newborn to 15 years. The defects generated were projected using an analytic projection code that models physical image degrading effects and were scaled with variations in organ uptake based on a new kinetic model fit to published data and parameters extracted from pediatric SPECT images. Combined with a previously-generated database of projections, the defect database will be used in image quality studies to determine the relationship between image quality, administered activity, and patient height and weight. In conjunction with already-calculated risk estimates, these will provide data to inform guidelines for pediatric dosing of DMSA.

Purpose Cardiovascular status was assessed in 48 Hodgkin's disease (HD) survivors at a median of 14.3 years (range, 5.9 to 27.5 years) after diagnosis because they may be at increased risk for cardiovascular abnormalities. Patients and Methods Patients completed the Short-Form 36 quality-of-life instrument and were screened by echocardiography, exercise stress testing, and resting and 24-hour ECG. Results All patients received mediastinal irradiation (median, 40.0 Gy; range, 27.0 to 51.7 Gy) at a median age of 16.5 years (range, 6.4 to 25.0 years). Four patients received an anthracycline. Although every patient described their health as good or better, and none had symptomatic heart disease at screening, all but one had cardiac abnormalities on screening. Restrictive cardiomyopathy was suggested by reduced average left ventricular (LV) dimension (P < .001) and mass (P < .001), without increased LV wall thickness. Significant valvular defects were present in 42%; 75% had conduction defects. One survivor developed complete heart block shortly after the study visit. Autonomic dysfunction was suggested by a monotonous heart rate in 57%, persistent tachycardia in 31%, and blunted hemodynamic responses to exercise in 27%. Peak oxygen uptake (VO2max) during exercise, a predictor of mortality in heart failure, was significantly reduced (< 20 mL/kg/m2) in 30% of survivors. VO2max was correlated with increasing fatigue, increasing shortness of breath (both, r = −0.35; P = .02), and decreasing physical component score on the SF-36 (r = 0.554; P = .00017). Conclusion A variety of unsuspected, clinically significant cardiovascular abnormalities are common in long-term survivors of HD who are treated at a young age with mediastinal irradiation. We recommend serial, comprehensive cardiac screening of HD survivors who fit this profile.

We evaluated whether findings on voiding cystourethrography suggesting ureteropelvic junction (UPJ) obstruction coexists with vesicoureteral reflux (VUR) are associated with parameters on dynamic renal scintigraphy that support significant obstruction.We reviewed records of 44 patients referred for scintigraphy after voiding cystourethrography performed at age 1 day to 9.4 years (mean 7 months, median 1.7 months) showed VUR and findings suggestive of UPJ obstruction (blockage of contrast material at the UPJ, contrast dilution in the renal pelvis, slow renal pelvic drainage). Results were correlated with Society for Fetal Urology hydronephrosis grade and ureteral morphology.Halftime was in the obstructive range (20 minutes or greater) for 7 of 47 kidneys (15%). The prevalence of a post-furosemide pelvicaliceal drainage halftime in the obstructive range increased with hydronephrosis grade (0% grade 1, 17% grade 2, 50% grade 3 to 4, p = 0.002) but did not vary with ureteral morphology (p = 0.08). In 12 of 38 cases (31%) where suspected UPJ obstruction was unilateral and a contralateral kidney was present differential uptake of the affected kidney was less than 45%. The prevalence of differential uptake less than 45% was higher in patients with than without ureteral dilatation (48% vs 12%, p = 0.02) but did not vary with hydronephrosis grade (p = 0.93).In children with VUR and suspected coexisting UPJ obstruction dynamic renal scintigraphy may support significant obstruction when hydronephrosis is at least moderate in degree or ureteral dilatation is present but is unlikely to do so if neither is observed.

Pediatric applications of nuclear medicine provide invaluable information in the diagnosis and follow-up of many disorders. However, radiopharmaceutical administered activities in children have not been standardized in North America until recently. Over the years, individual groups and institutions

Purpose: Expectations concerning the likelihood that vesicoureteral reflux will resolve during a given interval are predominantly based on experience with children younger than 5 years. We assess the natural course of vesicoureteral reflux in girls older than 5 years.Materials and Methods: We reviewed the diagnostic and followup cystograms, medical records and renal imaging studies of 200 girls with vesicoureteral reflux, of whom 97 were diagnosed before age 60 months and 103 were diagnosed at or after age 60 months. Vesicoureteral reflux was considered to have resolved when a followup radionuclide cystogram demonstrated no reflux.Results: Vesicoureteral reflux demonstrated at or after age 60 months by a radionuclide or radiographic examination (index study) resolved in 43% of cases during a mean followup interval of 41 months. The yearly percent chance of resolution approached or exceeded 20% through age 11 years. For girls with moderate vesicoureteral reflux on the index study unilateral moderate vesico...