Scintigraphic Imaging Research Articles

Isolated Cardiac Paraganglioma Encasing Right Coronary Artery With Evidence of Succinyl Dehydrogenase Gene Mutation: Successful Management Using Multimodality Imaging

This report involves a young woman with isolated cardiac paraganglioma that was diagnosed using 68Gallium-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-octreotide positron emission tomographic scintigraphy. For the preoperative evaluation, multimodality imaging accurately described the anatomic location of the tumor and its relationship with the surrounding tissues. The patient underwent successful surgical resection of the tumor along with right coronary artery bypass grafting. The 2-month follow-up scintigraphy was normal. Next-generation sequencing evaluation revealed a novel germline mutation for the succinate dehydrogenase subunit B gene.

Radiological and surgical correlation of pelviureteric junction obstruction in positional anomalies of the kidney in children.

Pelviureteric junction obstruction, also known as ureteropelvic junction obstruction, is a congenital narrowing of the urinary excretory tract at the junction between the renal pelvis and the ureter and is a common cause of congenital pelvicalyceal dilatation. The outcome is variable, from spontaneous resolution to renal parenchymal function loss in cases of untreated high-grade obstruction. Abnormalities in renal ascent, rotation and vascularity can be associated with pelviureteric junction obstruction and easily overlooked radiologically. In this pictorial review, we explore the anatomical, radiological and surgical correlations of pelviureteric junction obstruction in the context of a normal kidney and a spectrum of renal abnormalities, including hyper-rotation (also known as renal malrotation), failed renal ascent, fusion anomalies and accessory crossing renal vessels. For each scenario, we provide technical tips on how to identify the altered anatomy at the first ultrasound assessment and correlation with scintigraphic, cross-sectional and postoperative imaging where appropriate. A detailed ultrasound protocol specifically to assess and characterise pelviureteric junction obstruction in paediatric patients is also offered.

Study of technetium pertechnetate (99mTcO4) thyroid scintigraphy imaging among patients presenting with thyrotoxicosis at a tertiary care hospital in Kathmandu, Nepal

Background: Thyroid disorders represent an important public health problem worldwide. Excess thyroid hormone in the circulation due to any cause is termed as thyrotoxicosis. There are many causes of thyrotoxicosis, and it is important to find the cause as this will determine the management of the condition. 99mTcO4scintigraphy is diagnostic tool to differentiate various causes of thyrotoxicosis. This study aims to study the age and gender distribution of different causes of thyrotoxicosis.
 Methods: This is a retrospective analysis of technetium pertechnetate(99mTcO4) thyroid scintigraphy reports done of patients having thyrotoxicosis from the period of January 01, 2016, to December 31, 2016, at the Nuclear Medicine unit of National Academy of Medical Sciences, Bir Hospital, Kathmandu. Gender and age group analysis of the data was done using SPSS program.
 Results: A total of 211 reports of 99m TcO 4 thyroid scintigraphy were included in the study. There were 61 male patients and 150 female patients. Various causes of thyrotoxicosis like thyroiditis, Graves’ disease, autonomous functioning thyroid nodule, toxic multinodular goiter was detected. Apart from toxic multinodular goiter, these disorders were more common in the age group 18-50 years and females.
 Conclusion: 99mTcO4 thyroid scintigraphy is one of the easy and highly effective tools for the differential diagnosis of thyrotoxicosis. Both thyroiditis and Graves’ disease are more predominant in the age group 18-50 years and in females. Further large community-based studies will be required for exact prevalence of the diseases in the population.

517 RIGHT ATRIAL THROMBUS IN A PATIENT WITH CARDIAC AMYLOIDOSIS: A MULTIMODALITY IMAGING APPROACH

Abstract Case Presentation A 47-year-old man was referred to our outpatient clinic for dyspnea and chest pain. His past medical history was remarkable for an admission of acute congestive heart failure, occurred two weeks before presentation. On that occasion, the patient was discharged after a few days of diuretic therapy. Diagnostic Workup at presentation, the patient was symptomatic for dyspnea with signs of systemic congestion. The ECG showed sinus rhythm, inferolateral negative T waves and absent progression of R wave in precordial leads. Transthoracic echocardiography revealed markedly thickened left ventricular (LV) walls (maximum interventricular septum dimension 19 mm) with a granular-sparkling appearance of the myocardium, bi-atrial enlargement, preserved LV ejection fraction, restrictive mitral flow pattern thickened interatrial septum and atrio-ventricular valves. No significant valvular regurgitations were detected. Global LV longitudinal strain was significantly reduced (-9.4%), with relative apical sparing. Given the high suspicion for infiltrative disease we performed further investigations. The cardiac computed tomography (CCT) excluded significant coronary artery disease, but it raised the suspicion of a thrombus at the level of the right atrial appendage, that was confirmed by a transesophageal echocardiography showing a mobile round mass of 14×12 mm. Finally, tissue characterization by cardiac magnetic resonance exhibit a diffuse myocardial delayed enhancement, with a dark blood pool and, an increase in extracellular volume and T1 mapping values (1266.3 ms). Laboratory tests showed increased levels of creatinine, BNP and, lambda light chains. Bone scintigraphy imaging didn't identify any uptake of radiotracers at myocardial level. These findings were suggestive for cardiac light-chain (AL) amyloidosis. Accordingly, a treatment with warfarin, beta-blockers, steroid, and diuretics was initiated. Conclusions cardiac amyloidosis is an infiltrative disease characterized by the deposition of aggregates of amyloid fibrils in the myocardium. Multimodality imaging is pivotal to determine the diagnosis, assess the potential complications, and stratify the patients’ prognosis. Our case demonstrates that cardiac AL amyloidosis is associated with an increased thromboembolic risk, irrespective of the presence of atrial fibrillation. Moreover, although the left atrial appendage is most frequently the site of thrombus formation, it is advised to look for them also in uncommon sites as the right atrial appendage.

Comparison of the effect of miniaturized and standard percutaneous nephrolithotomy on renal function assessed with DMSA scintigraphy

Introduction and objectivesWe aimed to present a clinical study that compares standard and miniaturized percutaneous nephrolithotomy (PNL) effects on kidney function with scintigraphic imaging in primary kidney stone patients. Materials and methodsOne hundred four patients were included in this prospective study between May 2014 and February 2017. Eligible patients were divided into two groups miniaturized PNL (mPNL) and standard PNL (sPNL) with matched-pair analysis (1:1 scenario). Technetium-99m Dimercaptosuccinic Acid cortical scintigraphy imaging was performed before and after the operation. ResultsThere were no differences between the two groups in terms of success rate (mPNL (63.5%) vs. sPNL (71.2%), p=0.403), serum creatinine, glomerular filtration rate, split renal functions pre- and postoperatively (p≥0.05). There was no relationship between the type of operation and new scar formation (p=0.780). The rates of serious complication (grades 3 and 4 according to modified Clavien–Dindo Classification) were higher in sPNL (p=0.034). Stone burden, duration of operation, hemoglobin drop, multiple access, blood transfusion, and angioembolization were higher in patients with scarred kidneys (p<0.001, p=0.008, p=0.004, p<0.001, p=0.003, p=0.001, respectively). In multivariate analysis, only multiple access was found statistically significant for predicting new scar formation (p<0.001, OR: 24.28). ConclusionsMiniaturized and standard PNL are reliable and successful operations for treating large kidney stones. No significant difference was found between the operation types regarding a decrease in renal function.

Detection and Localisation of Abnormal Parathyroid Glands: An Explainable Deep Learning Approach

Parathyroid scintigraphy with 99mTc-sestamibi (MIBI) is an established technique for localising abnormal parathyroid glands (PGs). However, the identification and localisation of PGs require much attention from medical experts and are time-consuming. Artificial intelligence methods can offer an assisting solution. This retrospective study enrolled 632 patients who underwent parathyroid scintigraphy with double-phase and thyroid subtraction techniques. The study proposes a three-path approach, employing the state-of-the-art convolutional neural network called VGG19. Images input to the model involved a set of three scintigraphic images in each case: MIBI early phase, MIBI late phase, and 99mTcO4 thyroid scan. A medical expert’s diagnosis provided the ground truth for positive/negative results. Moreover, the visualised suggested areas of interest produced by the Grad-CAM algorithm are examined to evaluate the PG-level agreement between the model and the experts. Medical experts identified 545 abnormal glands in 452 patients. On a patient basis, the deep learning (DL) model attained an accuracy of 94.8% (sensitivity 93.8%; specificity 97.2%) in distinguishing normal from abnormal scintigraphic images. On a PG basis and in achieving identical positioning of the findings with the experts, the model correctly identified and localised 453/545 glands (83.1%) and yielded 101 false focal results (false positive rate 18.23%). Concerning surgical findings, the expert’s sensitivity was 89.68% on patients and 77.6% on a PG basis, while that of the model reached 84.5% and 67.6%, respectively. Deep learning in parathyroid scintigraphy can potentially assist medical experts in identifying abnormal findings.

Homing of radiolabelled xenogeneic equine peripheral blood-derived MSCs towards a joint lesion in a dog.

Osteoarthritis (OA) is a highly prevalent condition in dogs, causing a substantial reduction in quality of life and welfare of the animals. Current disease management focusses on pain relief but does not stop the progression of the disease. Therefore, mesenchymal stem cells (MSCs) could offer a promising disease modifying alternative. However, little is known about the behavior and the mode of action of MSCs following their administration. In the current case report, 99mTechnetium labelled xenogeneic equine peripheral blood-derived MSCs were intravenously injected in a 9 year old dog suffering from a natural occurring cranial cruciate ligament rupture. The biodistribution of the MSCs was evaluated during a 6-h follow-up period, using a full body scintigraphy imaging technique. No clinical abnormalities or ectopic tissue formations were detected throughout the study. A radiopharmaceutical uptake was present in the liver, heart, lung, spleen, kidneys and bladder of the dog. Furthermore, homing of the radiolabelled MSCs to the injured joint was observed, with 40.61 % higher uptake in the affected joint in comparison with the healthy contralateral joint. Finally, a local radioactive hotspot was seen at a part of the tail of the dog that had been injured recently. The current study is the first to confirm the homing of xenogeneic MSCs to a naturally occurring joint lesion after IV administration.

An automatic segmentation framework for computer-assisted renal scintigraphy procedure.

One of the techniques for achieving unique and reliable information in medicine is renal scintigraphy. A key step for quantitative renal scintigraphy is segmentation of the kidneys. Here, an automatic segmentation framework was proposed for computer-aided renal scintigraphy procedures. To extract kidney boundary in dynamic renal scintigraphic images, a multi-step approach was proposed. This technique is featured with key steps, namely, localization and segmentation. At first, the ROI of each kidney was estimated using Otsu's thresholding, anatomical constraint, and integral projection, which is done in an automatic process. Afterwards, the ROI obtained for the kidneys was used as the initial contours to create the final counter of kidneys using geometric active contours. At this step and for the segmentation, an improved variational level set was utilized through Mumford-Shah formulation. Using e.cam gamma camera system (SIEMENS), 30 data sets were used to assess the proposed method. By comparing the manually outlined borders, the performance of the proposed method was shown. Different measures were used to examine the performance. It was found that the proposed segmentation method managed to extract the kidney boundary in renal scintigraphic images. The proposed technique achieved a sensitivity of 95.15% and a specificity of 95.33%. In addition, the section under the curve in the ROC analysis was equal to 0.974. The proposed technique successfully segmented the renal contour in dynamic renal scintigraphy. Using all the data sets, a correct segmentation of the kidney was performed. In addition, the technique was successful with noisy and low-resolution images and challenging cases with close interfering activities such as liver and spleen activities.

Abstract 10063: Changes in Clinical Phenotype of Patients With ATTR Cardiac Amyloidosis During the Past 20 Years

Introduction: Diagnostic and therapeutic advances have led to increased awareness of transthyretin cardiac amyloidosis (ATTR-CA). We sought to characterise the change in clinical phenotype of patients with ATTR-CA over the last 20-years. Methods: We studied 1967 patients diagnosed with ATTR-CA at the National Amyloidosis Centre (NAC) from 2002-2021. Results: Analysis by 5-year quartiles revealed a substantial incremental increase in patients diagnosed, with the most marked increases seen in wild-type ATTR. Increased diagnoses were accompanied by greater proportions of patients referred following bone scintigraphy and cardiac magnetic resonance imaging (3% vs 44% vs 67% vs 76%, P&lt;0.001). Over time, median duration of symptoms prior to diagnosis diminished from 36-months between 2002-2006 to 12-months between 2017-2021 (P&lt;0.001) and a greater proportion of patients had milder disease at the time of diagnosis across the 5-yearly quartiles (NAC stage 1: 34% vs 42% vs 44% vs 53%, P&lt;0.001). The latter was associated with more favourable echocardiographic parameters of structure and function, including an incremental decrease in interventricular septal thickness(18.0±3.8mm vs 17.2±2.6mm vs 16.9±2.3mm vs 16.6±2.4mm, P=0.01), which was associated with improved survival. The improved survival associated with the year of diagnosis remained significant when censoring at trial or disease modifying medication start date (2012-2016 vs. 2017-2021: HR=1.05, 95%CI[1.03-1.07], P&lt;0.001). Conclusions: Increased awareness and advances in cardiac imaging have been associated with a substantial increase in diagnosis of ATTR-CA and at a progressively earlier stage of the disease, which has contributed to improved survival in recent years. These changes may have important implications for initiation and outcome of therapy and urgently need to be factored into clinical trial design.

Radiation dose measurement on bone scintigraphy and planning clinical management

Abstract Radiation has been used in a variety of different fields since its discovery. It is very important in medial sector for both diagnosis and also for treatment. In this study, the radiation dose rate emitted to the environment after radiopharmaceutical injection was determined using patients undergoing bone scintigraphy imaging. Radiation dose rate measurements were performed at different distances from the patient and at different levels of the patient. Measurements were done at different times to determine the relationship between radiation dose rate and time. The radiation dose rate emitted by the patient was measured after an average of 10.21, 42.36, and 76.28 min of injection. In order to see the relationship between radiation dose rate and distance, measurements were done at 25, 50, 100, and 200 cm distance from the patient. The measured average radiation dose rate at 1 m distance from the patients’ chest level and 10.21 min after radiopharmaceutical injection was 16.27 μSv h−1. Then, the average radiation dose rate decayed down to 13.65 μSv h−1 after 42.36 min, while the measured average radiation dose rate after 76.28 min was lower as 12.41 μSv h−1 at 100 cm from patient’s chest level.

Imaging Aerosol Deposition with Two-Dimensional Gamma Scintigraphy.

Several imaging modalities have been employed to quantify lung dose and the distribution of the dose of orally inhaled aerosols in vivo. Two-dimensional (2D, or planar) imaging using gamma scintigraphy is the most widely used of these modalities. Two-dimensional gamma scintigraphy studies are accomplished using a single- or dual-headed gamma camera. The formulation to be tested is admixed with the gamma emitting radioisotope 99mtechnetium, which serves as a surrogate for the drug. This article provides details as to how 2D gamma scintigraphy images should be acquired and analyzed using recently standardized methods. Based on the new guidelines, the investigator should confirm that the drug formulation is unchanged with the addition of the radioisotope, determine the amount of radioactivity needed for inhalation to obtain appropriate radioactivity counts in the lungs, perform quality control procedures for the gamma camera, identify the lung borders of the study subject using a reference image such as an X-ray computed tomography scan, a ventilation scan, or a transmission scan, acquire a lung transmission image to correct for attenuation of radioactivity by lung tissue, instruct the subject how to inhale the radiolabel-drug mixture and record associated breathing parameters, acquire anterior and/or posterior views of the lungs and any other regions of interest (i.e., oropharynx, stomach) and assess the acquired images for total and regional dose to the lungs. Total dose should be assessed after identification of the right lung border and appropriate correction for tissue attenuation. Regional dose should be quantified as a normalized outer/inner deposition ratio (O/I) and expressed as the penetration index (PI). Mass balance should be performed as needed. By following the standardized methods, 2D gamma scintigraphy data from studies in different laboratories may be compared and combined, leading to multi-center studies and more rapid development of new medications and devices for inhaled therapies.

RF24 | PSUN116 Once-weekly semaglutide delays a late phase gastric emptying of solid meal measured by repeated scintigraphic imaging in obese women with PCOS

Abstract Background GLP-1 agonism have the potential to affect gastric emptying (GE), yet the reports for subcutaneous semaglutide, currently the most effective GLP-1 RA approved for weight management, remain inconclusive. It has been demonstrated that once-weekly semaglutide either had no effect on GE or it delayed GE only within the first hour, without late phase retention. Notably, those conclusions were made by an indirect method of estimation of GE through ingestion, absorption and determination of plasma level of paracetamol. Furthermore, in most previous studies with once weekly semaglutide, GE has been evaluated as a part of the composite outcome. The indirect method with paracetamol was shown to be appropriate for evaluation of kinetics of liquid meals, whereas it might lead to inaccurate estimation of late phase GE. Scintigraphic evaluation is considered as a reference method for the purpose. Aim This is the first study that evaluates the effect of once weekly subcutaneous semaglutide on late phase GE of a solid meal by scintigraphy in obese women with PCOS without other comorbidities as a primary outcome. Materials and Methods A single-blind, placebo-controlled trial was conducted in 20 women with PCOS and obesity, without diabetes and other comorbidities, randomized to once weekly subcutaneous semaglutide 1 .0 mg (S) or placebo (P) for 8 weeks. Gastric emptying was assessed by scintigraphy after ingestion of 99mTC colloid in pancake labelled with radiopharmaceutical that maintained a stable binding within gastric environment by scintigraphy using sequential static imaging and dynamic acquisition. Estimation of GE was obtained by repeated imaging of remaining 99mTC activity (RA) at fixed time intervals over 4 hours and the half time (T1/2) of gastric emptying had been calculated. Additionally, we evaluated anthropometric, metabolic, hormonal and appetite parameters. Results At 30 min after ingestion significant difference in RA was observed between semaglutide group and placebo (92.5% in S vs. 89% in P (p=0,05)) and persisted throughout the observation period up to 4 hour (37% in S vs. 0% in P (p=0,002)). T1/2 was significantly longer in S as compared to P (171 min vs 118 min, respectively (p&amp;lt;0.001)). In addition, semaglutide led to significant decrease in weight, waist and neck circumference, HbA1c and androgen levels. Subjective ratings of appetite suppression correlated with T1/2. Conclusion Once weekly semaglutide 1.0 mg resulted in a significant late-phase retention of solid meal measured by repeated scintigraphic imaging. This effect correlated with appetite suppression and likely contributed to weight loss. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:18 p.m. - 1:23 p.m.

Histological validation of cardiac 99mTc-DPD uptake in patients with cardiac transthyretin amyloidosis

Abstract Background Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal disease caused by the extracellular deposition of misfolded ATTR protein in the myocardium. In an era where new therapies are rapidly emerging, development of non-invasive imaging modalities to quantify amyloid burden over time is of utmost importance. Although endomyocardial biopsy (EMB) remains the gold standard in amyloid detection and typing, 99mTc-DPD scintigraphy is a widely available and accurate tool for non-invasive diagnosis of cardiac ATTR amyloidosis. However, it remains to be determined whether the degree of cardiac 99mTc-DPD uptake correlates with the histological amyloid infiltration on EMB – thus, justifying 99mTc-DPD scintigraphy as a disease monitoring tool. Aim This single-centre observational study aimed to compare the extent of histologic amyloid burden on EMB with the quantification of cardiac 99mTc-DPD uptake on scintigraphic planar images and SPECT/CT acquisitions in cardiac ATTR amyloidosis. Methods 26 patients with cardiac ATTR amyloidosis were enrolled. Patients were included in case of (1) EMB-proven ATTR amyloidosis and (2) availability of 99mTc-DPD scintigraphy (reference activity: 550 MBq). Visual interpretation using the Perugini score, quantitative analysis of cardiac 99mTc-DPD uptake by planar whole-body imaging and SPECT/CT using regions of interest (ROI) were performed, and heart to whole-body ratio (H/WB) was measured. Histological amyloid load was quantified as percentage of the analysed myocardial tissue using Sulfated Alcyan Blue staining and the Fiji-ImageJ programme. Pearson's and Spearman's correlation were used for correlation analysis and assessment of agreement. Results ATTR patients had a median age of 77 [73–79] years and were predominantly male (85%). An abnormal Perugini score (i.e. 2 or 3) was present in 25 patients (96%), whereas 1 patient was assigned Perugini score 1 (4%). Increased cardiac tracer uptake was documented in all patients, both on 99mTc-DPD planar scintigraphy (ROImean 129±37) and SPECT/CT (ROImean 369±142). Histologic amyloid burden on EMB was 32±19% on average. It significantly correlated with Perugini score (r=0.56 p=0.003), as well as with cardiac 99mTc-DPD uptake (planar: r=0.54 p=0.006, SPECT/CT: r=0.48 p=0.018) and H/WB (r=0.41 p=0.046). Conclusion We have demonstrated a good correlation between histological amyloid infiltration on EMB and cardiac 99mTc-DPD uptake on scintigraphic planar images and SPECT/CT scans, illustrating the potential of 99mTc-DPD scintigraphy to yield reliable quantitative information on cardiac amyloid burden. Further investigations with a larger number of patients are needed to confirm our findings and to implement thresholds in cardiac 99mTc-DPD uptake for being used for guiding disease and therapy management. Funding Acknowledgement Type of funding sources: None.

S1058 A Scintigraphic Study to Evaluate the Safety, Tolerability, and Functions of a Drug Delivery System (DDS) Device in Healthy Subjects in Fasted State

Introduction: The clinical remission in moderate to severe ulcerative colitis (UC) and Crohn’s disease has plateaued at ∼15-20% even with the approval of multiple biologics/drugs. The ATLAS study demonstrated that the lack of adequate amount of drug at the diseased site is responsible for limited clinical benefit. The Drug Delivery System (DDS) is an ingestible electronic targeted delivery device containing a localization system to identify colon entry (S4 calls) based on the gastrointestinal (GI) anatomy and deliver a bolus dose of a therapeutic compound to the colon mucosa to improve efficacy and reduce systemic toxicity. This was an open-label and single-center study to evaluate the safety and tolerability, and functions of a DDS device using gamma scintigraphy in normal healthy volunteers (NHV) in the fasted state. Methods: Each subject was fasted overnight for a minimum of 8 hrs. and dosed with a single DDS device before resuming a normal diet at 4 hrs. post-dosing. Each capsule was filled with radioactive marker 111In-DTPA to identify DDS localization and to visualize payload release; water radiolabeled with 99mTc-DTPA was co-administered with the DDS to delineate GI landmarks by gamma scintigraphy. The GI transit of DDS and delivery location were confirmed by serial scintigraphy imaging and compared with the localization data in the recovered capsule. Results: Twelve male subjects were enrolled and treated in the study. There were no reported device-related adverse events in any subject who completed the study. GI transit metrics of DDS were consistent with GI residence times observed amongst NHV. There was no early release of the radio payload prior to S4 calls being made by all 12 devices. Ten of twelve devices (83%) showed correct localization calls in the colon, confirmed by scintigraphy image analysis. In addition, among devices that showed release of the 111In-DTPA payload, the dispersion of the radioactive marker completely covered the colon over time and spread to match the 99mTc-DTPA water coverage area from the site of DDS release throughout the remainder of the colon (Figure). Conclusion: This study demonstrated that DDS was well-tolerated and had a favorable safety profile, and the device functioned as intended in identifying and releasing drug payload in the colon. DDS provides more precise dosing with a liquid formulation at a pre-determined location in the GIT and delivers therapeutics to the site of disease to improve efficacy.Figure 1.: Cumulative distribution of radiotracer 111In-DTPA release from Drug Delivery System (DDS) post-dose A. the first release of 111In-DTPA was observed post-dose in the cecum/ascending colon. B. Distribution of released 111In-DTPA over time in the colon.

S1061 A Scintigraphic Study to Evaluate the Localization and Delivery Function of a Drug Delivery System (DDS) Device in Patients With Active Ulcerative Colitis (UC) in a Fasted State

Introduction: The clinical remission in moderate to severe ulcerative colitis (UC) and Crohn’s has plateaued at ∼15-20% even with the approval of multiple biologics/drugs. Altas study clearly demonstrated that the lack of adequate amount of drug at the diseased site is responsible for limited clinical benefit. The Drug Delivery System (DDS) is an ingestible electronic targeted delivery device containing a localization system to identify colon entry based on the gastrointestinal (GI) anatomy and deliver a bolus dose of a therapeutic compound to the colon mucosa to improve efficacy and reduce systemic toxicity. DDS was shown to be well-tolerated and functioned as intended in identifying and releasing radiotracer in the colon of normal healthy volunteers (NHV). Here, we aim to evaluate the safety and functionality of DDS in active UC patients in a fasted state. Methods: Patients with endoscopy and histology confirmed UC and active UC status defined as having Mayo score ≥ 2 or elevated Fecal Calprotectin Protein or high sensitivity C-reactive protein within one month of the screening visit were eligible for the study. Each patient was fasted overnight and dosed with a single DDS capsule prior to resuming a normal diet. Each capsule was filled with radioactive marker 111In-DTPA to independently identify DDS localization and to visualize payload release; water radiolabeled with 99mTc-DTPA was co-administered with the DDS to delineate GI landmarks by gamma scintigraphy. The GI transit of DDS and delivery location of the radiotracer were confirmed by serial gamma scintigraphy imaging. Results: This is a preliminary analysis of an ongoing study of active UC patients with Mayo scores between 3-8 enrolled and dosed in the study. GI transit metrics of DDS were consistent with the variable GI motility and the frequent bowel movements observed among active UC patients. DDS device demonstrated correct localization identification of colon entry and release of radiotracer in the colon regardless of variable GI motility, the level of inflammation, or blood in the colon of UC patients compared to NHV (Table), confirmed by gamma scintigraphy image analysis. The dispersion of the radiotracer adequately covered the colon from the site of release throughout the remainder of the colon. Conclusion: This result demonstrated that DDS functioned as intended in identifying and releasing the payload in the colon regardless of GI motility or disease status. Table 1. - GI transits, Residence Time, and Radiotracer (111In-DTPA) Delivery Location of DDS Device post-dose in Active UC patients (PM-602) and Normal Healthy Volunteers (NHV) (PM-601) Subject Mayo score Gastric emptying time (min) Small intestine Residence time (min) Arrival Time at Cecum (min) 1st Capsule release In-111 (min) Capsule location at the time of 1st capsule release Capsule Recovery Time (hrs) No. of Bowel Movements required to recover Capsule 602-116-001 6 104 169 273 324 Cecum 47.67 3 602-116-002 3 23 122 145 190 Cecum 26.50 3 602-116-003 8 38 292 330 354 Cecum 32.83 5 601-NHV (N = 11)* Median N/A 29 228 270 368 Cecum/Asc Colon/Splenic Flexure 23.99 1 (n=6)2 (n=4)3 (n=1) *Excluded one subject due to anomalous transit of the DDS device from the stomach to the duodenum and then back into the stomach.

Evaluation of activity kinetics in breast milk and calculation of the resulting effective radiation dose after 99mTc-MIBI scintigraphy of a breastfeeding women.

In breastfeeding women, the indication for scintigraphic imaging is strongly restricted due to potential transition of the radiopharmaceutical to the child via breast milk. The potential activity uptake of the breastfed child depends on the chemical compound of the radio pharmaceutical as well as biokinetics and metabolism in the maternal body. In the presented case 99mTc-MIBI scintigraphy was performed in a breastfeeding woman with sonographically suspicious thyroid nodules. Breastfeeding was interrupted for 30 hours and the breast milk during this period was collected and analysed to determine the excreted activity and the potentially resulting dose to the breastfed child. Activity concentration in the first breast milk sample (1.83 hours after administration of 500 MBq 99mTc-MIBI) was 380 Bq/mL, resulting in an absolute activity of 50 kBq for a sample size of 132 mL. Subsequently activity concentration decreased to 6 Bq/mL (29.8 hours p.i.). The calculated effective half-life of the secretion of 99mTc-MIBI via breast milk was 4.7 hours. The potentially resulting effective dose for the breastfed child was 13.4 µSv (ICRP80: dose coefficient: 0.13 mSv/MBq for 99mTc). Time activity curve showed a rapid decrease of the 99mTc-MIBI activity secreted to the breast milk. More than 90 % of the total secreted activity is attributable to the first 12 hours after administration. Therefore, an interruption of breastfeeding of 24 hours seems to be adequate.

99m Tc]Tc-HYNIC-EcgDf21: A defensin short analogue with potential application in infection foci imaging.

Opportunistic infections are a problem of great relevance in public health and the precise detection and localization of infection in the early stages of the disease is of great importance for patient management as well as cost containment. Our proposal seeks to contribute to developing a new agent that meets the needs of diagnosis and follow-up of fungal and bacterial infections, focused on the design of a radiotracer with the potential for recognition of hidden infection foci. Defensins are plant antimicrobial peptides that not only show activity against plant pathogens but also against human ones. A short analogue of EcgDf1 defensin, EcgDf21d (NH2 -ERFTGGHCRGFRRRCFCTKHC-COOH), was labelled through the formation of a 99m Tc-HYNIC complex which was assessed for physicochemical and biological behaviour both in vitro and in vivo. The [99m Tc]Tc-HYNIC-EcgDf21 labelling procedure rendered a single product with remarkably high RCP and stability in the labelling milieu. The Log p value indicated that [99m Tc]Tc-HYNIC-EcgDf21 has a hydrophilic behaviour, confirmed by the biodistribution profiles. The optimal uptake value was obtained for Candida albicans infection model reaching a lesion/muscle ratio of 3, this correlates with in vitro binding studies, and the lesion can be definitely observed in the scintigraphic images.

Bladder Paraganglioma Presenting as Post-Micturition Syncope.

A 22-year-old woman presented with a 12-year history of intensifying paroxysms of anxiety, palpitations and recurrent syncope following micturition. The patient was referred to endocrinology upon discovery of hypertension. An extended family history revealed metastatic phaeochromocytoma and paraganglioma in two grand-uncles. Clinical examination revealed hypertension, with a mean 24-hour ambulatory blood pressure of 150/100 mmHg. Supine plasma normetanephrines were markedly elevated with a raised 3-methoxytyramine, while plasma metanephrines were normal. Computed tomography identified a 4.4 cm mass at the right inferolateral margin of the bladder wall. Scintigraphic imaging confirmed unifocal bladder lesion uptake with no additional metastatic lesions. Following pre-operative alpha blockade, the patient underwent a partial cystectomy. Histology confirmed a paraganglioma, and SDHB staining was lost in neoplastic cells consistent with an SDHB-related paraganglioma. Plasma normetanephrine, 3-methoxytyramine and blood pressure returned to normal postoperatively. Genetic screening identified a germline heterozygous SDHB gene variant c.723C>G. Bladder paragangliomas are a rare but important differential to consider when investigating post-micturition syncope. An extended family history should be sought and suspicion for a genetic cause should be raised, especially when the condition presents at a young age. This is the first reported case describing phaeochromocytoma or paraganglioma with the SDHB gene variant c.723C>G.LEARNING POINTSBladder paragangliomas are a rare neuroendocrine tumour which should be considered when assessing patients with haematuria and hypertension, headache, palpitations, sweating and facial pallor with micturition.This case highlights the importance of a thorough clinical history with an extended family history and examination in the setting of micturition syncope, which can rarely occur with bladder paraganglioma.Young age at presentation, a family history of phaeochromocytoma and paraganglioma (PPGL), unusual paraganglioma location, mutifocality and aggressive disease should raise the suspicion for a genetic predisposition to PPGL.

99mTc-Pyrophosphate Scintigraphy Can Image Tracer Uptake in Skeletal Trunk Muscles of Transthyretin Cardiac Amyloidosis.

99mTc-pyrophosphate (99mTc-PYP) uptake in the skeletal muscles is minimal in patients with transthyretin cardiac amyloidosis (ATTR-CA) when assessed qualitatively and quantitatively. We previously demonstrated moderate- to high-grade 99mTc-PYP uptake in the subcutaneous abdominal fat of some patients with ATTR-CA and showed that this abnormal finding could reflect the regional amyloid burden of this tissue. We aimed to investigate the frequency of 99mTc-PYP uptake in skeletal trunk muscles of patients with ATTR-CA. Chest- and abdomen-centered 99mTc-PYP scintigraphy images were obtained 2 hours after IV injections of the tracer (20 mCi) in 36 patients with ATTR-CA. The frequency of 99mTc-PYP uptake in the following 11 skeletal trunk muscles was investigated: pectoralis major, deltoid, subscapularis, infraspinatus, trapezius, latissimus dorsi, erector spinae, psoas major, abdominal oblique, rectus abdominis, and the gluteus muscles. Ten of the 11 muscles were involved in patients with the highest number of 99mTc-PYP uptake in the skeletal trunk muscles examined, whereas no muscle was involved in a patient with the least uptake. The muscle with the highest rate of 99mTc-PYP uptake, observed in 34 of 36 patients (94.4%), was the abdominal oblique. No tracer uptake was observed in the psoas major. The frequency of radiotracer uptake in the remaining examined muscles was between those of abdominal oblique and psoas major muscles. Radiotracer uptake was often detectable in some skeletal trunk muscles of ATTR-CA, although the muscles of patients examined and the skeletal trunk muscles of 1 patient showed heterogeneity in the uptake of 99mTc-PYP.

Nuclear Molecular Imaging of Disease Burden and Response to Treatment for Cardiac Amyloidosis

Simple SummaryCardiac amyloidosis (CA) is characterized by extracellular infiltration and deposition of amyloid fibrils primarily derived from the circulating transthyretin protein (TTR) or immunoglobulin light chain (AL). With the development of non-invasive diagnostic approaches and the emergence of new pharmacotherapeutic treatments for CA, the transformative effects of bone scintigraphy have been important in diagnosing TTR-CA. Positron emission tomography (PET) imaging is another promising, non-invasive option for the diagnosis of CA and may help differentiate between ATTR and AL amyloidosis. Bone-seeking single-photon emission tomography/computed tomography (SPECT/CT) quantification and amyloid-targeting PET imaging could be useful as a new strategy for disease burden and therapy monitoring to provide more insights into therapy response assessed by quantifying the amyloid burden in CA.Cardiac amyloidosis (CA) is a heterogeneous group of diseases in which extracellular insoluble amyloid proteins are deposited in specific organs and tissues locally or systemically, thereby interfering with physiological function. Transthyretin protein (TTR) and light chain (AL) amyloidosis are the most common types of cardiac amyloidosis. Radionuclide bone scintigraphy has recently become the most common non-invasive test for the diagnosis of TTR-CA but is of limited value for the diagnosis of AL-CA. PET has proved promising for the diagnosis of CA and its applications are expected to expand in the future. This review summarizes the current bone scintigraphy and amyloid-targeting Positron emission tomography (PET) imaging, the binding imaging properties of radiotracers, and the values of diagnosis, prognosis, and monitoring therapy response in CA.