Radiotracer Uptake Research Articles

Longitudinal PET/CT Imaging with Iodine ( 124I) Evuzamitide Reveals Organ Response to Plasma Cell Immunotherapy in a Patient with AL Amyloidosis

Background:Iodine-124-evuzamitide is a novel amyloidophilic peptide (p5+14), labeled with iodine-124, for detecting amyloid by positron emission/x-ray computed tomographic (PET/CT) imaging ( Pharmaceuticals 2023 Apr 21;16(4):629). PET is an inherently quantitative modality and thus 124I-evuzamitide may be useful for monitoring disease progression and response to therapy. Amyloid deposits can impact any organ in patients with light chain-associated amyloidosis (AL); thus, tissue-specific changes in amyloid load, based on PET/CT imaging, may be informative. Currently, response to therapy is assessed by anatomic imaging and measurement of serum or urinary biomarkers. However, the correlation between these metrics and concomitant changes in amyloid load remains enigmatic. Here, we report a case of a patient with AL amyloidosis, on long-term daratumumab therapy, who underwent longitudinal 124I-evuzamitide PET/CT imaging over 4 years (NCT03678259 and NCT05968846). Patient and Methods: A 70-year-old male presented with abnormal liver function tests, notably an elevated serum alkaline phosphatase (ALK) of 465 IU/L. Biopsies of both the liver and celiac nodes revealed the characteristic apple-green birefringence of Congo red stain, indicating the presence of amyloid. The patient began daratumumab immunotherapy 14 months prior to his enrollment in the 124I-evuzamitide imaging study and over the 4-year course of serial imaging. During this time, regular serial serum biomarkers were evaluated as standard of care. PET/CT images were acquired at 0, 23, and 45 months. For each imaging session, the patient received 2 mCi iodine-124-labeled tracer via intravenous injection and was imaged at 5 h post injection. Image data were assessed for visual uptake of radiotracer and quantified by manual 2D region-of-interest analysis where the semi-quantitative mean standard uptake value ratio (SUVR mean) was calculated using blood pool as the reference tissue. Results: Over the 45 months of evaluation, there was a 59% and 73% reduction in 124I-evuzamitide SUVR in the liver and spleen. This was accompanied by decreases in the weight-scaled organ volume (cc/kg) for both the liver (15.2%) and spleen (30.0%) based on segmentation of the organ volume from CT images. This reduction in radiotracer uptake coincided with a sustained decrease in serum FLC, from 38.3 mg/L to 19.1 mg/L, and a positive liver response, where ALK levels dropped from ~200 IU/L to ~120 IU/L. In contrast, renal radiotracer uptake increased slightly in the context of stable creatinine levels, and a modest decline in eGFR. Cardiac uptake of 124I-evuzamitide remained positive and relatively stable, concordant with serum NT-proBNP levels. These data suggest that organ-specific amyloid response, in the context of a sustained hematologic response, may occur independently and at different rates. Conclusion: Previous reports have demonstrated the resolution of AL amyloid. However, this is the first report using an amyloid-binding radiotracer, capable of visualizing all major organs including the heart, demonstrating the complex pattern of organ response and regression of AL amyloid in the context of concurrent biomarker improvement and changes in organ volume. PET/CT imaging using 124I-evuzamitide may, therefore, play a valuable role in both diagnosing amyloidosis and monitoring changes in organ-specific amyloid load. Additional longitudinal imaging studies are needed to support this clinical application.

Fibroblast Activation Protein–Targeted PET/CT With Al18F-NODA-FAPI-04 for In Vivo Imaging of Tendon Healing in Rat Achilles Tendon Injury Models

Background: Fibroblast activation protein (FAP) has shown high expression in inflammatory responses and fibrosis. Hypothesis: We speculated that FAP could serve as a diagnostic and monitoring target in the tendon healing process. Study Design: Controlled laboratory study. Methods: A total of 72 Sprague-Dawley rats were randomly divided into a tendon crush group and a half-partial tendon laceration group. Four rats in each group were injected with radiotracers weekly for 4 weeks after surgery, with aluminum fluoride–labeled 1,4,7-triazacyclononane-N,N′,N″-triacetic acid–conjugated FAP inhibitor (Al18F-NODA-FAPI-04) administered on the first day of each week and 18F-fludeoxyglucose (18F-FDG) on the next day. Small animal positron emission tomography (PET) imaging was performed, and tendon tissue was collected for pathology and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis each week after surgery. Results: One week after surgery, both radiotracers showed signal concentration at the lesion site, which was the highest radioactive uptake observed during 4 weeks postoperatively, consistent with the severity of the lesion. Consistent trends were observed for inflammatory cytokines during qRT-PCR analysis. Additionally, Al18F-NODA-FAPI-04 PET exhibited a more precise lesion pattern, attributed to its high specificity for naive fibroblasts when referring to histological findings. Over time, the uptake of both radiotracers at the injury site gradually decreased, with 18F-FDG experiencing a more rapid decrease than Al18F-NODA-FAPI-04. In the fourth week after surgery, the maximum standardized uptake values of Al18F-NODA-FAPI-04 in the injured lesion almost reverted to the baseline levels, indicating a substantial decrease in naive fibroblasts and inflammatory cells and a reduction in inflammation and fibrosis, especially compared with the first week. Corresponding trends were also revealed in pathological and qRT-PCR results. Conclusion: Our findings suggest that inflammation is a prominent feature during the early stage of tendon injury. Al18F-NODA-FAPI-04 PET allows accurate localization and provides detailed morphological imaging, enabling continuous monitoring of the healing progress and assessment of injury severity.

Análisis de coste de pruebas de nueva generación en estadificación de pacientes con cáncer de próstata de alto riesgo

Introduction and objectiveNext-generation imaging tests, such as choline PET/CT and PSMA PET, have shown to increase sensitivity in the detection of nodal and metastatic disease in prostate cancer. However, their use implies an increase in diagnostic costs compared to conventional imaging (CI) tests such as CT and bone scan. The aim of our study was to determine which diagnostic pathway is more cost-effective in high-risk prostate cancer. Material and methodCost-effectiveness analysis of the available imaging tests (CI, Choline/PSMA PET) for the staging of high-risk prostate cancer. Sensitivity and specificity were estimated based on published evidence, and costs were collected from the Management Department. In order to carry out a cost-effectiveness analysis, five diagnostic pathways were proposed estimating the accurate diagnoses. ResultsPSMA PET was the most accurate diagnostic option. The CI diagnostic workup was the most economical and CI+PSMA the most expensive. Analyzing the diagnostic cost-effectiveness ratio, CI+PSMA proved to be the most expensive (€5627.30 per correct diagnosis) followed by PET PSMA (€4987.11), choline (€4599.84) and CI (€4444.22). ConclusionsPSMA PET is the most accurate strategy in staging distant disease in patients with high-risk prostate cancer. Radiotracer uptake tests such as CI have been shown to be the most cost-effective option, followed by choline and PSMA.

Longitudinal evaluation of cardiac and extracardiac amyloid load in patients with AL and ATTR amyloidosis, measured by 124I-AT-01 PET/CT imaging

Abstract Background The amyloid imaging agent, 124I-AT-01 (124I-p5+14), is being developed for the diagnosis and monitoring of amyloidosis, of any type, by PET/CT imaging (1,2). PET/CT is an intrinsically quantitative imaging modality, and this reagent could provide a facile, first-line method for the diagnosis of amyloidosis as well as permit quantitative longitudinal imaging for monitoring progression or regression of disease, notably in the heart, of all amyloid patients. Here we describe an interim analysis of a case series of AL and ATTR patients who have been imaged at least twice with 124I-AT-01 with a minimum of 12 months between imaging (NCT designation pending). Radiotracer uptake has been quantified for the heart, liver, spleen and kidneys and changes in uptake reported. Purpose The goal was to quantitatively assess changes in organ-specific radiotracer uptake in AL and ATTR patients with previous cardiac uptake using manual region-of-interest methods. Methods The study will enroll patients with AL (n=10) and ATTR (n=10) who were previously imaged more than 12 months prior and who had positive uptake of 124I-AT-01 in the heart. To date, six patients have been imaged twice and one has had three evaluations since 2019. Patients received 37 or 74 MBq 124I-AT-01 and PET/CT imaging was performed at ∼5 h post injection. A fully manual 2D region of interest analysis was performed on three representative image views of the heart in the transaxial plane as well as the liver, spleen and kidneys. The blood pool was used as a reference tissue to determine standard uptake value ratios (SUVRmean). Changes in cardiac uptake of radiotracer were compared with contemporaneous NTproBNP measurements. Results The PET images were of high quality and readily interpretable and quantifiable (Figure 1A). In this early analysis of the data, both AL (n=2) and ATTR (n=4) have been evaluated. The mean time between first and second imaging was 30.3 ± 8.9 months. In the patients with ATTR amyloidosis, there was an average of a 7.9 ± 10% decrease in cardiac uptake of 124I-AT-01 after an average of 32.5 months from the first scan, in patients on silencers or stabilizers. In the AL patients, one had a 10% decrease and the other a 12% decrease in heart uptake. In some, these changes correlated with serum NTproBNP levels. A notable decrease in 124I-AT-01 binding in both AL patients was observed in the liver (45% and 59%) and spleen (75% and 73%) with one example shown in Figure 1B. No cases of increased radiotracer uptake were observed in the heart, consistent with these patients being stabilised with standard of care therapy. Conclusion Changes in cardiac amyloid load, based on differential uptake of radiotracer, can be seen by longitudinal imaging and quantified using 124I-AT-01 PET/CT imaging. This technique may play a valuable role not only in the early and accurate diagnosis of amyloidosis but also for monitoring changes in organ-specific amyloid load.

Comparison of calculation algorithms between arithmetic mean of washout rate and total-count-based washout rate in single-photon emission computed tomography

Abstract Background Myocardial washout rate (WR) analysis of radiopharmaceuticals is utilized in nuclear cardiology to evaluate the clinical pathophysiology of the heart. WR is defined as the ratio of the difference between the count in the early image and the time-decay-corrected delayed image divided by the former. The arithmetic mean of washout rate (AMWR) of each segment is a commonly used algorithm for calculating WR from a polar map in single-photon emission computed tomography (SPECT). However, in this algorithm, uneven radiotracer uptake among segments affects WR calculation. Therefore, we newly formulated a modified algorithm for calculating WR based on the total count (TCWR). Purpose To clarify the usefulness of TCWR by comparing the calculation algorithms between TCWR and AMWR. Methods The WR of iodine-123-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) was calculated using TCWR and AMWR, and WR values using TCWR and AMWR were compared by disease. We focused on the patients with specific conditions that decreased BMIPP uptake in the early image — CD36 deficiency is a human loss-of-function genetic mutation model for BMIPP uptake, and old myocardial infarction (OMI) may present such a clinical phenotype. Also, patients with triglyceride deposit cardiomyovasculopathy (TGCV) were enrolled since a markedly decreased BMIPP WR (<10%) is one of the essential criteria for its diagnosis. Consecutive patients who underwent BMIPP scintigraphy were reviewed, and the analysis included patients without detectable cardiovascular diseases (normal) (n = 11), those with CD36 deficiency (n = 6), TGCV (n = 14), TGCV with OMI (n = 17), and non-TGCV with OMI (n = 10). Results WR values using TCWR and AMWR did not differ significantly in the following groups: normal, 27.4 ± 8.5 and 27.3 ± 8.5% (p = 0.97); CD36 deficiency, -3.2 ± 6.5 and -4.1 ± 7.4% (p = 0.81); TGCV, 2.4 ± 6.3 and 2.2 ± 6.3% (p = 0.93); and TGCV with OMI, -0.9 ± 7.6 and -3.7 ± 8.4% (p = 0.32). However, AMWR showed a lower WR than TCWR in non-TGCV with OMI (4.8 ± 8.7 and 18.9 ± 6.7%, p = 0.0008). Conclusions TCWR is suitable for calculating WR using SPECT polar maps even in cases with heterogeneous radiotracer uptake, such as OMIs. TCWR may be applied to measuring the WR of radiopharmaceuticals other than BMIPP in investigating the pathophysiology of heart diseases.Definition of calculation algorithms.Comparison of TCWR and AMWR.

Transthyretin amyloid cardiomyopathy among patients with hypertrophic cardiomyopathy: clinical, cardiac imaging, and electrocardiographic findings from the TTRACK study

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is often misdiagnosed as hypertrophic cardiomyopathy (HCM). Identifying ATTR-CM in patients with HCM is essential because treatment approaches vary, especially with the availability of disease-modifying therapies for ATTR-CM. In this analysis of the TTRACK study, we investigated clinical, cardiac imaging, and electrocardiogram (ECG) features of ATTR-CM that may heighten suspicion of amyloid disease and prompt further screening in patients with HCM. Purpose Explore the clinical, echocardiogram (echo), magnetic resonance imaging (MRI), and ECG findings of patients with HCM screened for ATTR-CM in the TTRACK study. Methods In this global, multicentre, non-interventional epidemiological study, the prevalence of ATTR-CM was assessed in patients ≥50 years of age with HCM of unknown aetiology (left ventricular [LV] maximum wall thickness ≥15 mm [echo]) using 99mTc-DPD/99mTc-PYP/99mTc-HMDP-labeled bone scintigraphy. Nuclear images were graded based on cardiac vs bone radiotracer uptake following the Perugini system. Monoclonal protein testing was performed to exclude light chain amyloidosis. Results Of 766 eligible patients with scintigraphy data, 521 (68.0%) had no cardiac uptake; 37 (4.8%) had low uptake (grade 1); and 208 (27.2%) had moderate/high uptake (grade 2/3). Among patients with moderate/high uptake (cardiac amyloidosis [CA]), 137 (65.9% of patients with CA; 17.9% of the overall cohort) had confirmed ATTR-CM. Comparing NYHA classification of patients with no cardiac uptake vs those with ATTR-CM, 33.8% and 25.0% were asymptomatic (NYHA class I). Marked numerical differences were observed in some echo findings of patients with no cardiac uptake vs ATTR-CM, including mean LV mass index (155.6 vs 177.0 g/m2) and the proportions of patients with preserved apical strain (57.9% vs 74.2%) and concentric hypertrophic pattern (38.8% vs 77.8%) (Table [A]). Although a smaller percentage of patients with ATTR-CM exhibited LV outflow tract (LVOT) obstruction than patients with no cardiac uptake, 12.5% of patients with ATTR-CM had LVOT obstruction (LVOT gradient >30 mmHg). A substantially lower proportion of patients with no cardiac uptake (54.7%) had late gadolinium enhancement on MRI than those with ATTR-CM (84.6%). Notable ECG differences were seen in PR interval (179.4 vs 196.9 ms) and the proportion with poor precordial R wave progression (21.9% vs 47.9%) (Table [B]). Conclusions In the TTRACK study, conducted in the largest cohort of patients with HCM ever screened for ATTR-CM, approximately 18% of patients ≥50 years of age with HCM had findings indicative of ATTR-CM. Noteworthy differences in some clinical, cardiac imaging, and ECG findings were seen between patients with HCM with and without ATTR-CM, but none appeared to be definitive. These findings suggest that broader screening for amyloid disease with scintigraphy should be considered among all patients with HCM.

Systemic Amyloid Response in Patients with AL Amyloidosis Assessed By Serial Iodine ( 124I) Evuzamitide PET/CT Imaging

Background: Immunoglobulin light chain (AL) amyloidosis is a systemic disorder. Fibrillar aggregates of monoclonal free light chains, or fragments thereof, can deposit in any organ or tissue. Invariably, more than one anatomic site is involved, including the heart, liver, spleen, kidneys, pancreas, nerves, gastrointestinal tract and vasculature. Cardiac and renal amyloidosis are clinically most ominous; however, amyloid in other sites significantly impacts quality of life and may cause other heretofore unappreciated clinical sequelae. This is also true of the other 17 types of systemic amyloidosis. The degree of amyloid distribution and the tissue-specific amyloid load can only be achieved by nuclear imaging. Moreover, monitoring changes in amyloid load in response to therapy would benefit from whole body quantitative molecular imaging techniques. Here we report a pilot study of eight ( n=8) patients with AL amyloidosis who underwent serial PET/CT imaging using a novel amyloid-binding, iodine-124-labelled peptide, designated iodine-124-evuzamitide. Data from a cohort of ten ( n=10) patients with transthyretin associated (ATTR) amyloidosis are also described for comparison (NCT05968846). Methods: The study plans to enroll 20 ( n=20) patients with AL ( n=10) and ATTR ( n=10) amyloidosis who were previously imaged more than 12 months prior and who had positive uptake of 124I-evuzamitide in the heart. To date, eight ( n=8) patients with AL and ten ( n=10) with ATTR amyloidosis have undergone repeat imaging since 2019. Between imaging sessions, patients with AL received immunotherapy ( n=2/8) or were untreated ( n=6/8). Patients were administered 37 or 74 MBq 124I-evuzamitide, and PET/CT imaging was performed at ~5 h post injection. Clinical chemistry parameters were collected contemporaneously. Images were interpreted by a single reviewer, experienced in evaluating this tracer, for positive uptake. A fully manual 2D region of interest (ROI) analysis was performed on three representative image views of the heart in the transaxial plane as well as the liver, spleen, and kidneys. The blood pool was used as a reference tissue to determine standard uptake value ratios (SUVR mean). Cardiac uptake of radiotracer was compared with serum NT-proBNP measurements. Pearson and Spearman correlations were used to test for associations. Results: The mean time between imaging sessions for patients with AL amyloidosis was 3.21±0.95 years and 2.96±0.87 years for the entire cohort. In the AL amyloid cohort, 88% ( n=7/8) had a reduction in cardiac radiotracer uptake. In one ( n=1) patient, a 92.9% increase in cardiac uptake was seen, which was readily visible in scaled maximum intensity PET images. In this patient, the liver, spleen, and kidney uptake also increased. In contrast to the heart, renal uptake of the radiotracer was increased in 62.5% ( n=5/8) of patients with AL, with three ( n=3) patients showing a >20% increase in the SUVR mean. A strongly positive, significant correlation between the change in the liver and spleen uptake was observed (Pearson r=0.88, p=0.004). The change in the cardiac radiotracer uptake correlated strongly with that of the spleen (Pearson r=0.74, p=0.04). For the entire cohort, AL and ATTR patients ( n=18), there was a significant moderate correlation between the change in cardiac SUVR mean and change in single point serum NTproBNP concentration (Spearman rho=0.57, p=0.01). Conclusion: AL amyloidosis, and indeed all types of systemic amyloid disease, is a complex systemic disorder. The amyloid response to treatment, or disease progression, remains enigmatic as compared to the hematologic and biomarker responses. Appreciating the changes in amyloid load may not only improve clinical management but may also illuminate aspects of pathogenesis. PET/CT imaging using 124I-evuzamitide may, therefore, play a valuable role in understanding, diagnosing, and monitoring changes in organ-specific amyloid load and amyloid response. Additional longitudinal imaging studies are needed to investigate these possibilities further.

Structural and Functional Cardiac Parameters in Patients with AL Amyloidosis Correlate with Uptake of the Amyloidophilic Radiotracer Iodine ( 124I) Evuzamitide

Background: The deposition of fibrillar aggregates of monoclonal free light chains in the heart is a characteristic feature of light chain associated (AL) amyloidosis. Cardiac amyloid is the major cause of morbidity and mortality in these patients. Structural and functional sequelae of cardiac amyloidosis can be appreciated clinically using echocardiography, cardiac magnetic resonance imaging, and measurement of serum NT-proBNP and troponins. These measures are not particularly amyloid-specific, and the correlation between parameters derived from these evaluations and amyloid burden remain enigmatic. The iodine-124 labeled peptide (p5+14), iodine ( 124I) evuzamitide, is a novel radiotracer that is being evaluated for the detection of systemic amyloidosis, of any type, by PET/CT imaging. As an amyloid binding peptide, this radiotracer has the potential to serve as a first line diagnostic agent capable of providing whole body semi-quantitative estimation of organ-specific amyloid load. Nascent studies of the relationship between 124I-evuzamitide uptake and established clinical parameters in patients with amyloidosis are underway. Here we report a single site, open label pilot study of 18 ( n=18) patients with AL ( n=8) and ATTR amyloidosis ( n=10) that evaluates the cardiac uptake of 124I-evuzamitide with contemporaneous echocardiographic and serum biomarkers (NCT05968846). Methods: The data described herein was collected as part of an open label single site repeat imaging study that plans to enroll up to 20 ( n=20) patients with AL ( n=10) and ATTR ( n=10) amyloidosis. To date, eight ( n=8) patients with AL and ten ( n=10) with ATTR amyloidosis have undergone 124I-evuzamitide PET/CT imaging with contemporaneous transthoracic echocardiography and assessment of serum NTproBNP within ~30 h of imaging. Patients received 37 or 74 MBq 124I-evuzamitide, and PET/CT imaging was performed at ~5 h post injection. Images were interpreted by a single reviewer, experienced in evaluating this tracer, for positive cardiac uptake. A fully manual 2D region of interest (ROI) analysis was performed encompassing the free left ventricular (LV) wall, LV lumen and interventricular septum (IVS). Blood pool was used as a reference tissue to determine standard uptake value ratios (SUVR mean) and to control for the rate of tracer clearance from the central compartment. Cardiac uptake of radiotracer was compared with free LV wall thickness (cm), IVS thickness (cm), global longitudinal strain (GLS, %), and serum NT-proBNP (pg/mL) measurements. Pearson and Spearman correlations were used to test for associations between variables. Results: Patients with AL amyloidosis were 2012 Mayo Stage I ( n=2/8) or Stage II ( n=6/8). The mean serum NTproBNP was 672.9±762.4 pg/mL (min=98, max=2327). With singular exception, all patients with AL amyloidosis had visually evident cardiac uptake of 124I-evuzamitide in the PET/CT images. In patients with AL amyloidosis ( n=8), the SUVR mean (encompassing the LV, lumen and IVS) correlated strongly with LV thickness (cm) (Pearson r=0.83, p=0.011) and GLS (%) (Pearson r=0.74, p=0.037), but not the IVS thickness (cm) (Pearson r=0.57, p=0.142). In contrast, in patients with ATTR ( n=10), there was no significant correlation of SUVR mean with GLS ( p=0.395), but a moderate significant correlation of SUVR mean with the LV ( p=0.037) and IVS ( p=0.017) thickness was observed. Similarly, in this pilot cohort, we observed a strong positive correlation between serum NTproBNP and cardiac SUVR mean (Pearson r=0.81, p=0.015), but not for patients with ATTR amyloidosis (Pearson r=0.58, p=0.079). Conclusion: Serum NTproBNP is a validated and qualified measure of overall survival for patients with AL amyloidosis (PMID: 27416985). Global longitudinal strain, with or without inclusion of other structural parameters such as left atrial volume, is a strong predictor of survival in patients with AL amyloidosis (PMID: 29111123, PMID: 37143609). PET/CT imaging using 124I-evuzamitide is a promising technique for diagnosing and monitoring AL and other types of amyloidosis. In light of these early results that demonstrate a strong relationship between validated metrics of all cause mortality in patients with AL, larger studies should seek to evaluate similar relationships with some metric of 124I-evuzamitide uptake in the heart, and indeed other organs.

Cardiac Amyloid Detection by PET/CT Imaging of Iodine (124I) Evuzamitide (124I-p5+14): A Phase 1/2 Study

BackgroundThe noninvasive detection of cardiac amyloid, as well as deposits in other vital organs, is critical for early diagnosis and quantitative disease monitoring. Positron emission tomography is an intrinsically quantitative imaging modality suitable for high-resolution amyloid detection. ObjectivesThis study sought to evaluate the safety and efficacy of a novel amyloid-reactive peptide, designated p5+14, labeled with iodine-124 (124I), in patients with diverse types of systemic amyloidosis. MethodsIn a single-site, open label phase 1/2 study (NCT03678259), the safety, biodistribution, and sensitivity of a single intravenous infusion of 124I-evuzamitide was assessed in patients with systemic amyloidosis (n = 50), asymptomatic transthyretin sequence variant carriers (n = 2), and healthy volunteers (n = 5). Subjects were administered 1.4 ± 0.2 mg of 124I-evuzamitide (71.5 ± 12.4 MBq) and positron emission tomography/x-ray computed tomography images acquired at 5.2 hours (Q25-Q75: 4.9-5.4 hours) postinfusion. Images were assessed visually and semi-quantitatively for positive uptake of radiotracer in the heart and other major organs. ResultsUptake of 124I-evuzamitide in the heart and other abdominothoracic organs was consistent with the patient’s clinical presentation and the type of amyloidosis. The patient- and cardiac-associated sensitivity for imaging and clinical observations was 93.6% (95% CI: 82.8%-97.8%) and 96.2% (95% CI: 81.8%-99.8%), respectively. Semi-quantitative uptake of the radiotracer correlated significantly with serum N-terminal pro–B-type natriuretic peptide measurements in patients with light chain–associated amyloidosis. Cardiac uptake was not observed in any healthy volunteers. The agent was well tolerated, with 1 drug-related adverse event and no deaths. Conclusions124I-evuzamitide is an amyloid-binding radiotracer capable of detecting cardiac amyloid in patients with high sensitivity.

Initial evaluation and external validation of 68Ga-PSMA-11 PET/CT in tubarial gland characterization

IntroductionRadiotracer 68Ga-PSMA-11 used in PET/CT scans allows for identification and localization of gland tissue. It allows for their consideration in clinical scenarios and to design further and stronger research to answer pertinent questions regarding their function and implications. We aimed to externally validate first reported findings of location, size, and ligand uptake of the tubarial glands using 68Ga-PSMA-11 PET/CT. Materials and MethodsA cross-sectional study was performed with 68Ga-PSMA-11 PET/CT studies of patients with prostate cancer confirmed diagnosis from the database of the Radiology Department from 2018 to 2022. The maximum cephalocaudal length (CCL) in the tubarial glands and the Maximum Standardized Uptake Value (SUVmax) of major glands were recorded. ResultsA total of 202 patients were included (mean age 67.43 ± 8.5). The mean CCL of the tubarial glands was 37.38 ± 9.84 and a SUVmax of 6.56 ± 2.14. The rest of the glands were as follows: parotid 15.12 ± 4.43, submandibular 16.82 ± 5.43 and sublingual 5.84 ± 3.24. No differences were found between laterality. A weak correlation between age and SUVmax of tubarial glands was identified. Tubarial glands had a similar 68Ga-PSMA-11 uptake to that of sublingual glands. ConclusionThis study corroborates the existence of a conglomerate of glands in the nasopharynx roof, near the posterolateral pharyngeal recess. It serves as validation in a different population with similar results in previous research. Without 68GA-PSMA-11 PET/CT the abundance, configuration and potential clinical relevance of these glands would probably not have been identified. Radiotracer uptake was similar amongst the major salivary glands, with a more similar uptake to that shown by the sublingual gland.

Sacroiliac Joint Index in Healthy Pakistani Population and Patients with Sacroiliitis Using Technetium-99m Methylene Diphosphonate Bone Scintigraphy

Objective: To determine the values of the Sacroiliac Joint Index (SI Index) in normal population and patients with sacroiliitis (SI) and the correlation of normal values with age and gender. Study Design: Prospective longitudinal study. Place and Duration of Study: Nuclear Medical Centre, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Dec 2020 to Jul 2022. Methodology: A total of 140 patients (Group-I consisting of 129 cancer patients having no clinical or radiological evidence of SI referred for metastatic/staging workup and Group-II consisting of 11 patients with clinical, laboratory and radiological diagnosis of ankylosing spondylitis) who underwent whole body bone scintigraphy using Technetium Pertechnetate (Tc-99m) labelled Methylene Diphosphonate (MDP) were included. The SI Index was calculated for each patient using the sacroiliac joint (SIJ) to sacrum radiotracer uptake ratio using the ROI method. Results: The mean SI Index was 1.02±0.09, (range: 0.87-1.24) in normal individuals while 1.28±0.09 (range: 1.15-1.53) in patients with SI. A significant statistical difference was observed in both groups for the SI Index (p-<0.001). In addition, the SI Index was significantly associated with age (p=0.016) in the normal population. Conclusion: The SI Index quantification using bone scintigraphy is a sensitive and cost-effective method for detecting SI. In addition, the SI Index differs according to age, so a different cut-off value should be used for each group.

Incidental 68Ga-DOTATATE uptake in thyroid nodules: Is guideline-directed management still appropriate?

BackgroundFluorodeoxyglucose uptake on positron emission tomography imaging has been shown to be an independent risk factor for malignancy in thyroid nodules. More recently, a new positron emission tomography radiotracer—Gallium-68 DOTATATE—has gained popularity as a sensitive method to detect neuroendocrine tumors. With greater availability of this imaging, incidental Gallium-68 DOTATATE uptake in the thyroid gland has increased. It is unclear whether current guideline-directed management of thyroid nodules remains appropriate in those that are Gallium-68 DOTATATE avid. MethodsWe retrospectively reviewed Gallium-68 DOTATATE positron emission tomography scans performed at our institution from 2012 to 2022. Patients with incidental focal Gallium-68 DOTATATE uptake in the thyroid gland were included. Fine needle aspiration biopsies were characterized via the Bethesda System for Reporting Thyroid Cytopathology. Bethesda III/IV nodules underwent molecular testing (ThyroSeq v3), and malignancy risk ≥50% was considered positive. ResultsIn total, 1,176 Gallium-68 DOTATATE PET scans were reviewed across 837 unique patients. Fifty-three (6.3%) patients demonstrated focal Gallium-68 DOTATATE thyroid uptake. Nine patients were imaged for known medullary thyroid cancer. Forty-four patients had incidental radiotracer uptake in the thyroid and were included in our study. Patients included in the study were predominantly female sex (75%), with an average age of 62.9 ± 13.9 years and a maximum standardized uptake value in the thyroid of 7.3 ± 5.3. Frequent indications for imaging included neuroendocrine tumors of the small bowel (n = 17), lung (n = 8), and pancreas (n = 7). Thirty-three patients underwent subsequent thyroid ultrasound. Sonographic findings warranted biopsy in 24 patients, of which 3 were lost to follow-up. Cytopathology and molecular testing results are as follows: 12 Bethesda II (57.1%), 6 Bethesda III/ThyroSeq-negative (28.6%), 1 Bethesda III/ThyroSeq-positive (4.8%), 2 Bethesda V/VI (9.5%). Four nodules were resected, revealing 2 papillary thyroid cancers, 1 neoplasm with papillary-like nuclear features, and 1 follicular adenoma. There was no difference in maximum standardized uptake value between benign and malignant nodules (7.0 ± 4.6 vs 13.1 ± 5.7, P = .106). Overall, the malignancy rate among patients with sonography and appropriate follow-up was 6.7% (2/30). Among patients with cyto- or histopathology, the malignancy rate was 9.5% (2/21). There were no incidental cases of medullary thyroid cancer. ConclusionThe malignancy rate among thyroid nodules with incidental Gallium-68 DOTATATE uptake is comparable to rates reported among thyroid nodules in the general population. Guideline-directed management of thyroid nodules remains appropriate in those with incidental Gallium-68 DOTATATE uptake.

Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution.

Various cellular sources hamper interpretation of positron emission tomography (PET) biomarkers in the tumor microenvironment (TME). We developed an approach of immunomagnetic cell sorting after in vivo radiotracer injection (scRadiotracing) with three-dimensional (3D) histology to dissect the cellular allocation of PET signals in the TME. In mice with implanted glioblastoma, translocator protein (TSPO) radiotracer uptake per tumor cell was higher compared to tumor-associated microglia/macrophages (TAMs), validated by protein levels. Translation of in vitro scRadiotracing to patients with glioma immediately after tumor resection confirmed higher single-cell TSPO tracer uptake of tumor cells compared to immune cells. Across species, cellular radiotracer uptake explained the heterogeneity of individual TSPO-PET signals. In consideration of cellular tracer uptake and cell type abundance, tumor cells were the main contributor to TSPO enrichment in glioblastoma; however, proteomics identified potential PET targets highly specific for TAMs. Combining cellular tracer uptake measures with 3D histology facilitates precise allocation of PET signals and serves to validate emerging novel TAM-specific radioligands.

SAT534 A Rare Case of Poorly Differentiated Thyroid Cancer With Extraordinary Limitations to Treatment

Abstract Disclosure: N. Shahid: None. L. Rudman: None. H. Maldonado Rivera: None. J. Chambi-Torres: None. J.A. Gonzalez: None. S. Valepu: None. A. Barco: None. N.H. Shaaban: None. E. Angueira: None. Background: Poorly differentiated thyroid cancer (PDTC) is a rare and aggressive form of follicular epithelial cell derived thyroid carcinoma, representing 3-5% of all thyroid cancers. As a subtype, PDTC is in a category that is between well differentiated thyrocyte malignancies and undifferentiated (anaplastic) thyroid carcinomas. Current guidelines for treatment of PDTC are not well defined. Case presentation: A 56-year-old male with a history of PDTC was admitted to the hospital directly from a correctional facility due to concern for metastasis. Patient had a total thyroidectomy performed just two months ago that revealed PDTC on surgical pathology. Recommendations at that time were to complete a full body PET-CT and follow up with radiation oncology for radiation and chemotherapy. Patient was also discharged on Synthroid 175 mcg daily for TSH suppression. However, the patient did not have any follow up appointments scheduled while at the facility. PET-CT showed stable FDG avid 2.4 cm lower right neck mass and 2 cm focus of mildly increased activity in the right lobe of the liver. On admission, a triple phase MRI liver protocol was ordered and showed a 15 mm hepatic lesion that was arterially enhancing with persistent enhancement in venous and delayed phase without dropping signal on T2 fat and additional hyperintensity on T2. Bilateral 1.7 cm adrenal nodule was also identified with relative hypointensity on T2. FNA of right neck mass was performed but did not yield sufficient tissue for pathology. Subsequent right neck exploration and skin biopsies were obtained and revealed benign fibroadipose tissue with focal fat necrosis in the thyroid and lobular capillary hemangioma in right back, left chest, and right abdomen. Patient’s status as an inmate continued to delay radiation and chemotherapy for PDTC with possible metastasis. The decision was made with the hematology/oncology inpatient consult team to perform RAI treatment with 138 mCI of I-131. Synthroid was held in anticipation of the RAI and whole body scan was ordered for 1 week after administration of I-131. Post ablation whole body scan showed intense radiotracer uptake over the region of the left and right thyroid glands and normal uptake in the stomach, small bowel, and urinary bladder. No other areas of radiotracer uptake were found. Conclusion: Diagnosis and treatment of PDTC is challenging and the social constraints as an inmate make it even more difficult to initiate appropriate therapy with radiation oncology follow up. Our case illustrates the implications of RAI ablation after total thyroidectomy in staging and therapy of PDTC. Given the intermediate histologic characteristics of PDTC, further investigation is required in the setting of metastasis and exploration of the benefits of early aggressive therapy, such as external beam radiotherapy. Presentation Date: Saturday, June 17, 2023

Uptake of 68Ga-PSMA in Avascular Necrosis of the Femoral Head in a Patient With Prostate Cancer.

A 69-year-old man with prostate cancer treated with radical prostatectomy underwent 68Ga-PSMA PET/CT due to biochemical recurrence. Increased radiotracer uptake in the prostate bed suggestive of local recurrence was detected. The right hip also displayed increased 68Ga-PSMA activity, which was consistent with the avascular necrosis findings on MRI.

FRI263 Challenges In Management Of Biochemically Silent Pheochromocytoma

Abstract Disclosure: G. Gannamani: None. T. Gourdin: None. J.K. Fernandes: None. Background: Incidental adrenal tumors are a common radiological finding. Biochemical work up is important as functioning adrenal tumors increase mortality and morbidity. Missing diagnosis of Pheochromocytoma can result in fatal outcomes. There have been case reports with asymptomatic and mildly elevated biochemical markers or symptomatic but no biochemical evidence which pose challenges in diagnosis. Here we describe a case of Metastatic Pheochromocytoma which was biochemically silent. Case Description: 61-year-old female with incidental finding of left adrenal mass measuring 8.7 x 5.6 x 5.7 cm on CT (Computed Tomography) scan for back pain 10 years prior to presentation. She was told no further testing was needed then as she was asymptomatic. She now has uncontrolled hypertension requiring multiple anti-hypertensives that prompted further work up. Biochemical work up at outside facility reported as normal aldosterone, renin activity, AM cortisol, ACTH, DHEA-S, plasma metanephrine and normetanephrine, epinephrine, norepinephrine, and dopamine. Elevated Chromogranin A of 5608 (normal < 93 ng/mL). Repeat CT Abdomen showed multiple enhancing lesions in liver, large lobulated adrenal mass measuring 15 x 10 x 14 cm (previously 8.7 x 5.6 x 5.7 cm) with central necrosis, absolute washout is 63%. This mass extended into gastro-hepatic space, obliterating fat space between the left adrenal mass and tail of pancreas was also reported. Imaging was concerning adrenal malignancy vs Pheochromocytoma. Further work up with MRI (Magnetic Resonance Imaging) Abdomen showed 14 cm centrally necrotic mass suggestive of adrenal neoplasm with loco-regional involvement. CT chest with bilateral pulmonary nodules and diffuse sclerotic and lucent bone lesions concerning osseous metastatic disease. Liver biopsy positive for metastatic neuroendocrine neoplasm consistent with Pheochromocytoma, immunohistochemical stains positive for Synaptophysin, Chromogranin, S100, GATA3, Inhibin. Dotatate PET CT with large centrally necrotic left adrenal mass. Abnormal radiotracer uptake in left kidney, stomach, gastrohepatic lymph nodes, widespread osseous lesions suggesting metastatic disease. She was not a surgical candidate given extension of mass and metastasis to multiple organs. Treatment started with Sunitinib (Tyrosine kinase inhibitor), plan to repeat imaging in 4-6 months hoping for tumor shrinkage.

FRI504 Ectopic Hyperactive Mediastinal Thyroid Tissue: A Case Report

Abstract Disclosure: C. Dimech: None. G. Jaiswal: None. A. Bhargava: None. Ectopic thyroid tissue is usually located along the normal path of the caudal migration of thyroid tissue during embryonic life. Substernal goiters are thought to occur by either the enlargement of ectopic mediastinal thyroid tissue (primary mediastinal goiter) or abnormal extension of thyroid issue into the superior mediastinum (secondary mediastinal goiter). Typically these goiters remain asymptomatic, and rarely result in hyperthyroidism or local compression of the surrounding area. We report a case of an 89-year-old Caucasian female with history of a multinodular goiter status post right hemithyroidectomy, who initially presented for subclinical hyperthyroidism. Further evaluation revealed negative thyroid stimulating antibodies. A thyroid ultrasound demonstrated a surgically absent right lobe, with a small heterogenous left lobe. A nuclear medicine radioactive iodine uptake and scan showed hypermetabolic residual thyroid tissue with a large area of increased radiotracer uptake projecting over the right anterior chest, concerning for ectopic thyroid tissue. A subsequent chest CT without contrast revealed an approximately 5 centimeter partially calcified anterior mediastinal/retrosternal mass. Given the patient’s age and co-morbidities, a decision was made to treat the hyperthyroidism with methimazole and monitor the ectopic tissue for worsening symptoms of compression. In cases with severe compressive symptoms, or difficult to treat hyperthyroidism, a surgical option must be considered. Presentation: Friday, June 16, 2023

THU665 Unilateral Graves’ Disease In A Bilobar Thyroid Gland: Unusual Cause Of Hyperthyroidism

Abstract Disclosure: K.H. Alaybaa: None. O. Alhuzaim: None. Introduction: Graves' disease (GD) is an autoimmune condition that affects both thyroid gland lobes. GD patients with unilateral thyroid scan uptake are rare. These patients present with classic Graves' symptoms, occasionally with Graves' ophthalmopathy characteristics and increased thyroid hormones, and scintigraphic assessment reveals radiotracer uptake in only one lobe of the thyroid gland. Patient Findings: In this case, a 48-year-old female presented with symptoms and signs indicative of thyrotoxicosis. Lab results revealed that thyroid-stimulating hormone (TSH) was undetectable, while free thyroxine (T4) and free triiodothyronine (T3) were in the high-normal range. Positive results were observed for both thyroid-stimulating immunoglobulin and TSH receptor antibodies. Ultrasonography of the thyroid gland revealed an enlarged left lobe with heterogeneous echotexture and a hyperemic gland without any focal lesions, distinct nodules, or cysts. The NM TC-99M thyroid scintigraphy revealed enlarged and increased radioisotopes uptake in the left thyroid lobe and decreased uptake in the right thyroid lobe, with no hot or cold nodules. The calculated thyroid uptake is 4.5 percent (normal range: 0.5% to 3.5 percent). The most likely diagnosis was unilateral GD. The patient was administered carbimazole and within eight weeks had improved clinically and biochemically. Summary: This patient has thyrotoxicosis symptoms and positive autoantibodies. Tc99m uptake was increased in the left thyroid lobe and decreased in the right thyroid lobe. The left thyroid lobe was hypervascular and enlarged on ultrasonography, indicating the presence of unilateral GD. Unilateral GD is a rare disease with a poorly understood pathophysiology. Presentation: Thursday, June 15, 2023

FRI260 Adrenal Hemangioma, Mimicker Or Malignant?

Abstract Disclosure: C. Pham: None. C.E. Chiu: None. B. Barnett: None. Background: Adrenal hemangioma is a rare condition that can mimic other adrenal pathologies. Clinical Case: A 49 year old male with history of heart failure presented with cardiogenic shock requiring inotropes and heart transplant evaluation. On CT patient was noted to have a 2.2 cm left adrenal nodule containing calcifications. Initial tests had indeterminate 1 mg overnight DST, normal plasma free metanephrines and elevated plasma free normetanephrines 2.06 nmol/L (0-0.89 nmol/L). PRA was 22.82 ng/mL/hr (0.25-5.82 ng/ml/hr) with aldosterone 10.8 ng/dL (<16 ng/dL) on spironolactone. 24 hour urine tests showed normal free cortisol 9.8 mcg/24hr (4-50 mcg/24hr) and elevated total metanephrines at 1245 mcg/24hr (182-739 mcg/24hr), metanephrines at 303 mcg/24hr (58-283 mcg/24hr), and normetanephrines at 942 mcg/24hr (88-649 mcg/24hr). Adrenal CT demonstrated HU of 59 units on noncontrast phase, with -86.7% absolute washout and -17.6% relative washout. I-123 MIBG Scan was obtained with no radiotracer uptake noted. Patient underwent laparoscopic adrenalectomy for definitive diagnosis and was found to have adrenal hemangioma with CD31 and ERG with hemosiderin laden macrophages on pathology. Adrenal hemangioma is rare and can mimic other adrenal pathology. Most patients present with abdominal symptoms such as flank pain or are found to have an adrenal incidentaloma on imaging. CT findings are associated with heterogenous internal structure, peripheral patchy enhancement, or calcifications, which are also seen in malignancy and pheochromocytoma. In all cases, HU if recorded are noted to be >10 on the unenhanced phase and <60% absolute washout. In one case series of 52 adrenal hemangiomas, only 3 patients had positive biochemical tests and on average were 11 cm in size. Formal diagnosis is made pathologically. Treatment for adrenal hemangioma is typically resection for symptomatic relief, with some patients with small lesions electing to observe. In all surgical cases reviewed in a case series adrenalectomy was pursued as opposed to needle biopsy due to large size of lesion and concern for possible malignancy. In this specific case, biochemical testing was falsely positive given the patient’s presentation of cardiogenic shock and inotropes causing elevated catecholamine levels and given imaging findings could not fully rule out pheochromocytoma. Given the small size of lesion, the patient in a non-transplant setting likely could have pursued close observation as opposed to resection. Conclusion: Adrenal hemangioma can have imaging characteristics that can mimic several other adrenal pathological conditions, such as malignancy or pheochromocytoma. Treatment through surgical management is likely not necessary in patients with hemangioma, though would be important in ruling out other adrenal pathology. Presentation: Friday, June 16, 2023

The Biodistribution and Utility of 99mTc-Ethylenedicysteine-Deoxyglucose (99mTc-Glucosamine) in the Identification of Active Disease in Patients with Rheumatoid Arthritis—a Single Center Prospective Study

PurposeOur objectives were to investigate the utility of 99mTc-ethylenedicysteine-deoxyglucose (ECDG) in identifying active disease in the joints of patients with rheumatoid arthritis (RA), as well as to evaluate the biodistribution of this radiopharmaceutical.MethodsA prospective study was conducted at the Department of Nuclear Medicine of the University of the Free State/Universitas Academic Hospital in Bloemfontein, South Africa. Twenty-two participants from the rheumatology department diagnosed with RA according to the ACR/EULAR classification criteria were enrolled. Participants were injected with 20–25 mCi of 99mTc-ECDG. Flow, blood pool, whole body, delayed static, and SPECT/CT images were acquired. Known sites of disease were qualitatively assessed for intensity of uptake, and disease severity was graded (Grade 0–3).ResultsTwenty-two participants were studied. The median (interquartile range) age was 59 (49–68) years, and the majority (n = 21; 95.5%) were females. There was abnormal increased uptake of 99mTc-ECDG noted in majority of the sites of known disease, including unknown sites. SPECT/CT imaging localized radiotracer uptake specifically to the synovial space. Similar biodistribution of radiotracer was noted in all patients, irrespective of disease severity or fasting status.Conclusion99mTc-ECDG can efficiently assess disease activity in the joints of patients with RA. It accumulates in sites of both clinical and subclinical disease and might be a very useful tool for the rheumatologist in the management of patients with RA.