Diphosphonate Scintigraphy Research Articles

18F]-florbetaben PET/CT is sensitive for cardiac AL amyloidosis.

Often differential diagnosis between AL and ATTR amyloidosis is difficult. Concerning ATTR, sensitive diagnostic tool, as diphosphonate scintigraphy, was validated, instead of no imaging approach is as accurate in AL. Cardiac ultrasound and circulating biomarkers may raise the clinical suspicion but biopsy remains the only option for diagnosis. We aimed to explore the sensitivity of 18F-Florbetaben PET respect to blood tests or periumbilical fat (POF), cardiac, bone marrow (BM) or other tissues biopsies in a cohort of 33 patients.

DON’T FORGET ABOUT CARDIAC AMYLOIDOSIS: WHEN RED FLAGS MATTER

Abstract Case Report A 78–year–old man came to our attention for worsening dyspnea, asthenia and frequent lipothymic episodes in the last few weeks. Nothing remarkable was reported in anamnesis except for periodic cardiological check–ups ascribed to hypertensive heart disease and moderate aortic stenosis. Other cardiovascular risk factors were obesity, previous smoking habits and dyslipidemia. A recent 24–hours ECG monitoring revealed slow permanent atrial fibrillation (AF) with 3–seconds pauses, frequent premature ventricular complexes (PVCs) and some PVCs couplets. On arrival, NT–proBNP was elevated (2952 pg/mL), while ECG showed AF with a heart rate of 50/m and low voltages in peripheral leads. Transthoracic echocardiogram revealed a biatrial dilatation, a severe left ventricular (LV) concentric hypertrophy with a preserved LV ejection fraction (EF) and a moderate aortic stenosis. In addition, a restrictive LV filling pattern, a decreased longitudinal myocardial contraction and an apical sparing of longitudinal strain were reported. Invasive coronary angiography was performed with evidence of normal coronary arteries. Given the echocardiographic suspicion of amyloidosis, a 99mTc–Hydroxymethylene diphosphonate (HMDP) scintigraphy was performed, showing a moderate cardiac uptake and an attenuated bone uptake (Perugini Score 2). Serum and urine immunofixation resulted negative. Genetic testing did not find any mutations in Transthyretin (TTR) gene. Therefore, the diagnosis of TTR wild–type amyloidosis was made. Before discharge, putting it all together, we opted to implant a leadless pacemaker in order to protect the patient from life–threatening bradyarrhythmias. Discussion Although it is currently considered rare, there is growing evidence that cardiac amyloidosis may be more common than once thought. First of all, it should be investigated in HFpEF–patients (heart failure with preserved EF) with LV hypertrophy. Despite several red flags (low QRS voltages, conduction disorders, elevated NT–proBNP, severe LV hypertrophy and aortic stenosis) and various medical consultations, our patient had to wait 4 years or more to be diagnosed with cardiac amyloidosis. Inevitably, a diagnostic delay means loss of time in treatment initiation. Earlier diagnosis would enable us to improve our patients’ survival and heart failure hospitalization. Awareness alone is not enough, we must be right on target too.

All that illuminates on radionuclide imaging is not a metastatic lesion: Role of complementary imaging

Radionuclide imaging is a non-invasive modality based on tracer physiology widely utilized in the diagnosis, staging, therapeutic evaluation, and monitoring of metastatic disease in a spectrum of malignancies. Calcific tendinopathy is a well-recognized disorder related to the deposition of calcium hydroxyapatite crystals within tendons. We describe a patient with urothelial carcinoma of the bladder revealing increased uptake at the left hip on 99mTc labeled methylene diphosphonate scintigraphy suggesting a metastatic lesion. Cross-sectional imaging with magnetic resonance imaging confirmed the accurate diagnosis of calcific tendinopathy of gluteus maximus insertion. This case report highlights the importance of a thorough clinical evaluation and complementary imaging in assessing benign pathologies which may mimic metastatic bone lesions.

Prevalence and prognosis of cardiac amyloidosis in patients who underwent diphosphonate scintigraphy for non-cardiological reasons

Transthyretin cardiac amyloidosis is a rare and currently underdiagnosed disease. Untreated, median survival since diagnosis is estimated to be between 3 and 5 years. Diphosphonate scintigraphy is one of the earliest positive examinations well before biological or clinical signs. The objective of this study is to determine the prevalence of cardiac involvement in patients who underwent disphophonate scintigraphy for non-cardiological reasons and to follow their prognosis. Our study is a retrospective, descriptive, monocentric study carried out at the university hospital of Poitiers. Collection of all scintigraphy with Technetium 99m-labelled disodium Hydroxymethylene Diphosphonate (HMDP-99mTc), performed at the Poitiers University Hospital between January 1, 2006 and January 1, 2012. 725 patients were included and all scintigraphy were reanalyzed and we retained only the Perugini 2 and 3 stage for the diagnosis of amyloidosis. The study focuses on the prevalence and the overall and detailed mortality of these patients at 5 years. In all, 20 scintigraphy showed Perugini scores of 2 or 3, i.e., a prevalence of about 1% in the study. The prevalence by age group was also studied: there is an age-related gradient: among patients over 70 years of age, it is calculated at 2.7% (20/725 patients); among patients over 80 years of age, it is calculated at 4.4% (14/316) (Fig. 1); and among patients over 90 years of age, it is calculated at 16.7% (4/24). No fixation was found in patients under 70-years-old. The overall 5-year mortality rate was calculated at 85%, the majority of which was due to cancer. The discovery of Perugini stage 2 and 3 cardiac staining on scintigraphy for non-cardiological reasons among the 725 patients analyzed is uncommon (1%). There is an age-related prevalence gradient (up to 16.7% over 90 years). Radiologists should refer patients to amyloidosis specialists for specific management, which would allow amyloidosis to be managed at an early stage to probably decrease hospitalizations and mortality.

Prevalence of amyloid transthyretin cardiomyopathy in elderly subjects from the general population: first results from the CATCH study

Abstract Background Amyloid transthyretin cardiomyopathy (ATTR-CM) has become treatable. Wild-type ATTR-CM is an age-related disorder. Establishing the exact prevalence of ATTR-CM in elderly subjects from the general population may be useful for healthcare providers and policy makers alike. Methods The Characterizing the burden of Amyloid Transthyretin CardiomyopatHy in the elderly (CATCH) study is a population screening on all subjects aged ≥65 years followed by general practitioners working in a part of Tuscany (Italy) where there is no cluster of variant ATTR. The study started on March 12, 2021 and is ongoing. The first step of the evaluation includes clinical history and physical examination, electrocardiogram, transthoracic echocardiogram, and blood sampling with measurement of N-terminal pro-B-type natriuretic peptide and high-sensitivity (hs) troponin T. The following elements are searched: 1) any clinical red flag of amyloidosis (history of carpal tunnel syndrome, lumbar spine stenosis, etc.), 2) interventricular septal thickness ≥12 mm or other echocardiographic red flags, 3) hs-troponin T higher than the upper reference limit (14 ng/L). Patients with any of these elements are referred to a second step including diphosphonate scintigraphy and the search for a monoclonal protein in the serum and urine. The standard diagnostic workup for CA is then followed until the diagnosis is confirmed or discarded. Results As of October 13, 2021, 514 subjects ≥65 years have been evaluated for possible participation. Among them, 135 (26%) could not be contacted, were reluctant to enter the study, died before being contacted, or were bedridden. Out of the other 379 subjects, 329 (87%) have already undergone the first step. Forty percent of individuals (n=132) have been referred to the second step. Thirteen subjects have declined (10%); 69 patients have undergone diphosphonate scintigraphy and the search for a monoclonal protein (while the other 50 are awaiting these exams). Two subjects showed an intense myocardial uptake of the diphosphonate tracer (Perugini score 2–3) and no monoclonal protein, and were then diagnosed with ATTR-CM. They were both women, aged 83 and 78 years, both mildly symptomatic for dyspnea (New York Heart Association II) and with unexplained hypertrophy. The search for TTR gene mutation was negative in the first case and is still ongoing in the second. Based on these preliminary data, the prevalence of ATTR-CM in the elderly population can be calculated as 2/266=0.8% (Figure 1). Conclusions The CATCH study is expected to enroll at least 1,000 subjects and will provide the first data on the epidemiology of ATTR-CM in elderly subjects. Based on an interim analysis, almost 1 in 100 individuals ≥65 years has ATTR-CM. Funding Acknowledgement Type of funding sources: None.

P288 PREVALENCE OF AMYLOID TRANSTHYRETIN CARDIOMYOPATHY IN ELDERLY SUBJECTS FROM THE GENERAL POPULATION: FIRST RESULTS FROM THE CATCH STUDY

Abstract Background Amyloid transthyretin cardiomyopathy (ATTR–CM) has become treatable. Wild–type ATTR–CM is an age–related disorder. Establishing the exact prevalence of ATTR–CM in elderly subjects from the general population may be useful for healthcare providers and policy makers. Methods The Characterizing the burden of Amyloid Transthyretin CardiomyopatHy in the elderly (CATCH) study is a population screening on all subjects aged ≥65 years followed by general practitioners in a part of Tuscany (Italy) where there is no cluster of variant ATTR. The study started on March 12, 2021 and is ongoing. Patients with 1) any clinical red flag of amyloidosis, 2) interventricular septal thickness ≥12 mm or other echocardiographic red flags, and/or 3) hs–troponin T > 14 ng/L are referred to diphosphonate scintigraphy and search for a monoclonal protein. Results As of October 13, 2021, 514 subjects ≥65 years have been evaluated for possible participation. Among them, 135 (26%) could not be contacted, were reluctant to enter the study, died before being contacted, or were bedridden. Out of the other 379 subjects, 329 (87%) have already undergone the first step. Forty percent of individuals (n = 132) have been referred to the second step. Thirteen subjects have declined (10%); 69 patients have undergone diphosphonate scintigraphy and the search for a monoclonal protein (while the other 50 are awaiting these exams). Two subjects showed an intense myocardial uptake of the diphosphonate tracer (Perugini score 2–3) and no monoclonal protein, and were then diagnosed with ATTR–CM. They were both women, aged 83 and 78 years, both mildly symptomatic for dyspnea (New York Heart Association II) and with unexplained hypertrophy. The search for TTR gene mutation was negative in the first case and is still ongoing in the second. Based on these preliminary data, the prevalence of ATTR–CM in the elderly population can be calculated as 2/266=0.8%. Conclusions The CATCH study is expected to enroll at least 1,000 subjects and will provide the first data on the epidemiology of ATTR–CM in elderly subjects. Based on an interim analysis, almost 1 in 100 individuals ≥65 years has ATTR–CM.

Convolutional neural networks for detection of transthyretin amyloidosis in 2D scintigraphy images

BackgroundTransthyretin amyloidosis (ATTR) is a progressive disease which can be diagnosed non-invasively using bone avid [99mTc]-labeled radiotracers. Thus, ATTR is also an occasional incidental finding on bone scintigraphy. In this study, we trained convolutional neural networks (CNN) to automatically detect and classify ATTR from scintigraphy images. The study population consisted of 1334 patients who underwent [99mTc]-labeled hydroxymethylene diphosphonate (HMDP) scintigraphy and were visually graded using Perugini grades (grades 0–3). A total of 47 patients had visual grade ≥ 2 which was considered positive for ATTR. Two custom-made CNN architectures were trained to discriminate between the four Perugini grades of cardiac uptake. The classification performance was compared to four state-of-the-art CNN models.ResultsOur CNN models performed better than, or equally well as, the state-of-the-art models in detection and classification of cardiac uptake. Both models achieved area under the curve (AUC) ≥ 0.85 in the four-class Perugini grade classification. Accuracy was good in detection of negative vs. positive ATTR patients (grade < 2 vs grade ≥ 2, AUC > 0.88) and high-grade cardiac uptake vs. other patients (grade < 3 vs. grade 3, AUC = 0.94). Maximum activation maps demonstrated that the automated deep learning models were focused on detecting the myocardium and not extracardiac features.ConclusionAutomated convolutional neural networks can accurately detect and classify different grades of cardiac uptake on bone scintigraphy. The CNN models are focused on clinically relevant image features. Automated screening of bone scintigraphy images using CNN could improve the early diagnosis of ATTR.

541 Prevalence of amyloid transthyretin cardiomyopathy in elderly subjects from the general population: first results from the catch study

Abstract Aims Amyloid transthyretin cardiomyopathy (ATTR-CM) has become treatable. Wild-type ATTR-CM is an age-related disorder. Establishing the exact prevalence of ATTR-CM in elderly subjects from the general population may be useful for healthcare providers and policy makers alike. Methods and results The characterizing the burden of Amyloid Transthyretin CardiomyopatHy in the elderly (CATCH) study is a population screening on all subjects aged ≥65 years followed by general practitioners working at the Casa della Salute in Terricciola, in an area of Tuscany where there is no cluster of variant ATTR. The study started on 12 March 2021 and is ongoing. The first step of the evaluation includes clinical history and physical examination, electrocardiogram, transthoracic echocardiogram, and blood sampling with measurement of N-terminal pro-B-type natriuretic peptide and high-sensitivity (hs) troponin T. The following elements are searched: (i) any clinical red flag of amyloidosis (history of carpal tunnel syndrome, lumbar spine stenosis, etc.), (ii) interventricular septal thickness ≥12 mm or other echocardiographic red flags, and (iii) hs-troponin T higher than the upper reference limit (14 ng/l). Patients with any of these elements are referred to a second step including diphosphonate scintigraphy and the search for a monoclonal protein in the serum and urine. The standard diagnostic workup for CA is then followed until the diagnosis is confirmed or discarded. As of 31 October 2021, 514 subjects ≥65 years have been evaluated for possible participation. Among them, 135 (26%) could not be contacted, were reluctant to enter the study, died before being contacted, or were bedridden. Out of the other 379 subjects, 329 (87%) have already undergone the first step. Forty percent of individuals (n = 132) have been referred to the second step. Thirteen subjects have declined (10%); 69 patients have undergone diphosphonate scintigraphy, and the search for a monoclonal protein (while the other 50 are awaiting these exams). Two subjects showed an intense myocardial uptake of the diphosphonate tracer (Perugini score 2–3) and no monoclonal protein, and were then diagnosed with ATTR-CM. They were both women, aged 83 and 78 years, both mildly symptomatic for dyspnoea (New York Heart Association II) and with unexplained hypertrophy. The search for TTR gene mutation was negative in the first case and is still ongoing in the second. Based on these preliminary data, the prevalence of ATTR-CM in the elderly population can be calculated as 2/266 = 0.8% (Figure). Conclusions The CATCH study is expected to enroll at least 1000 subjects and will provide the first data on the epidemiology of ATTR-CM in elderly subjects. Based on an interim analysis, almost 1 in 100 individuals ≥65 years has ATTR-CM.

High-sensitivity cardiac troponin T and NT-proBNP for ruling-in and ruling-out of cardiac amyloidosis

Abstract Background Cardiac amyloidosis (CA) is caused by the extracellular deposition of misfolded proteins into insoluble amyloid fibrils, the 2 most common forms being transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis. Chronic elevation of cardiac troponins and natriuretic peptides is common in CA and predicts worse outcome. The diagnostic yield of biomarkers of cardiac damage for CA has been less investigated. Purpose We aimed to evaluate the ruling-in/out values for the diagnosis of CA of high-sensitivity cardiac troponin T (hs-cTnT) and of N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP). Methods We studied 275 consecutive patients referred to two tertiary Centers in Italy (n=184) and France (n=91) with the clinical suspicion of CA due to the presence of a plasma cell dyscrasia or an unexplained left ventricular (pseudo)hypertrophy. CA was confirmed by the combination of suggestive features on imaging techniques (echocardiography, cardiac magnetic resonance, diphosphonate scintigraphy) and biopsy examination. All patients underwent a full baseline characterization including hs-cTnT and NT-proBNP. Biomarkers values corresponding to a negative likelihood ratio &amp;lt;0.1 or a positive likelihood ratio &amp;gt;10 were respectively chosen as rule-out and rule-in cut-offs for CA. Results CA was confirmed in 161 (59%) patients, who had either AL amyloidosis (n=96, 60%) or ATTR amyloidosis (n=65, 40%). At time of evaluation, 97 (35%) patients (34 CA vs. 63 controls, p=0.112) were hospitalized for decompensated heart failure. Patients with CA showed higher hs-cTnT (65 ng/L [44–122] vs. 31 [18–42], p&amp;lt;0.001) and NT-proBNP (4260 ng/L [2006–8911] vs. 1199 [468–3357], p&amp;lt;0.001) than those without CA. The area under the curve (AUC) values for hs-cTnT and NT-proBNP were 0.832 and 0.744 respectively (p=0.002 for the difference). The combination of the two biomarkers (AUC=0.836) improved discrimination over NT-proBNP (p=0.004), but not over hs-cTnT (p=0.423). A hs-cTnT value &amp;lt;15 ng/L (sensitivity=100%, negative predictive value=100%, true negatives=13, false negatives=0) and a NT-proBNP &amp;lt;550 ng/L (sensitivity=98%, negative predictive value=89%, true negatives=33, false negatives=4) were selected as rule-out cut-offs. A hs-cTnT level ≥80 ng/L (specificity=96%, positive predictive value=93%, true positives=71, false positives=5) was optimal for ruling in amyloidosis, while no rule-in cut-off could be selected for NT-proBNP. hs-cTnT values of either ≥80 or &amp;lt;15 ng/dL could effectively rule-in/out 89 (32%) patients. Conclusions Plasma hs-cTnT and NT-proBNP have diagnostic value in patients with suspected CA. Stand-alone hs-cTnT levels &amp;lt;15 or ≥80 ng/L may help to exclude or confirm the diagnosis of CA in up to one third of patients undergoing a diagnostic screening for the disease. Figure 1 Funding Acknowledgement Type of funding source: None

Diphosphonate single-photon emission computed tomography in cardiac transthyretin amyloidosis

Abstract Background Planar diphosphonate scintigraphy is an established diagnostic tool for amyloid transthyretin (ATTR) cardiomyopathy. Characterization of the amyloid burden up to the segmental level by single photon emission computed tomography (SPECT) has not been evaluated so far. Methods Data from consecutive patients undergoing cardiac 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) SPECT and diagnosed with ATTR cardiomyopathy at a tertiary referral center from June 2016 to April 2019 were collected. Results Thirty-eight patients were included (median age 81 years, 79% men, 92% with wild-type ATTR). In patients with Perugini score 1, the most intense diphosphonate regional uptake was found in septal segments, particularly in infero-septal segments. Among patients scoring 2, the amyloid burden in the septum became more significant, and extended to inferior and apical segments. Finally, patients scoring 3 displayed an intense and widespread tracer uptake. All patients with Perugini score 1 had LGE in at least one antero-septal, one infero-septal, and one infero-lateral segment. All patients with score 2 displayed LGE in infero-septal, inferior, and infero-lateral segments. LGE became extensive in patients scoring 3, with all patients having at least one LGE-positive segment in each region. Conclusions When assimilating different Perugini grades to evolutive stages of the disease, amyloid deposition seem to progress from the septum to the inferior wall and then to the other regions and from the basis to the apex. The potential of segmental analysis might be particularly relevant in patients with very limited cardiac uptake at planar scintigraphy (Perugini score 1). Funding Acknowledgement Type of funding source: None

Diphosphonate single-photon emission computed tomography in cardiac transthyretin amyloidosis

BackgroundPlanar diphosphonate scintigraphy is an established diagnostic tool for amyloid transthyretin (ATTR) cardiomyopathy. Characterization of the amyloid burden up to the segmental level by single photon emission computed tomography (SPECT) has not been evaluated so far. MethodsData from consecutive patients undergoing cardiac 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) SPECT and diagnosed with ATTR cardiomyopathy at a tertiary referral center from June 2016 to April 2019 were collected. ResultsThirty-eight patients were included (median age 81 years, 79% men, 92% with wild-type ATTR). In patients with Perugini score 1, the most intense diphosphonate regional uptake was found in septal segments, particularly in infero-septal segments. Among patients scoring 2, the amyloid burden in the septum became more significant, and extended to inferior and apical segments. Finally, patients scoring 3 displayed an intense and widespread tracer uptake. All patients with Perugini score 1 had LGE in at least one antero-septal, one infero-septal, and one infero-lateral segment. All patients with score 2 displayed LGE in infero-septal, inferior, and infero-lateral segments. LGE became extensive in patients scoring 3, with all patients having at least one LGE-positive segment in each region. ConclusionsWhen assimilating different Perugini grades to evolutive stages of the disease, amyloid deposition seem to progress from the septum to the inferior wall and then to the other regions and from the basis to the apex. The potential of segmental analysis might be particularly relevant in patients with very limited cardiac uptake at planar scintigraphy (Perugini score 1).

Skeletal Changes in Hypoparathyroidism: X-ray to Bone Scintigraphy.

Parathyroid hormone (PTH) is a key in maintaining calcium homeostasis. Decreased PTH will result in decreased bone remodeling and increased bone density. The major cause is iatrogenic injury to parathyroid gland. X-ray and dual-energy X-ray absorptiometry are used to identify the skeletal changes. Typical skeletal changes are metaphyseal sclerosis in long bones and sclerosis of vertebrae and pelvic bones. 99mTc methylene diphosphonate scintigraphy is used to identify metabolic bone diseases. There are no typical scan findings in case of hypoparathyroidism. We like to report an interesting image of skeletal scintigraphy in case of hypoparathyroidism.

P2729NT-proBNP and high-sensitivity cardiac troponin T to diagnose cardiac amyloidosis

Abstract Background Cardiac amyloidosis (CA) is characterized by the accumulation of misfolded proteins into amyloid fibrils, leading to cardiomyocyte toxicity, extracellular volume expansion and ventricular pseudohypertrophy. As a consequence of such processes, natriuretic peptides and cardiac troponins are chronically elevated in CA and hold significant prognostic value. The diagnostic yield of these biomarkers for CA has never been explored so far. Methods Plasma levels of N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured in 230 patients referred to a tertiary centre with the clinical suspicion of cardiac amyloidosis. The final diagnosis was established according to current protocols, which include clinical, electrocardiographic, biohumoral, instrumental (echocardiography, cardiac magnetic resonance, diphosphonate scintigraphy), and biopsy examinations. Results Patients were aged 79 (interquartile interval 73–83) years and were predominantly males (n=147, 64%). Mean left ventricular (LV) ejection fraction was 55% (48–62%), and mean LV mass indexed was 150 (120–178) g/m2. CA was confirmed in 86 patients (37%), who had either light chain (AL) amyloidosis (n=25, 29%) or transthyretin (ATTR) amyloidosis (n=61, 71%). Alternative diagnoses were hypertensive cardiopathy (n=69, 48%), valvular disease (n=27, 19%), hypertrophic cardiomyopathy (n=18, 13%), or left ventricular hypertrophy with unknown or multifactorial mechanisms. Patients with CA showed higher NT-proBNP (5507 ng/L [2348–10326] vs. 1332 [392–3752], p&lt;0.001) and hs-cTnT (65 ng/L [48–114] vs. 35 [21–52], p&lt;0.001) than those without CA. The area under the curve (AUC) values for NT-proBNP and hs-cTnT were 0.712 and 0.775 respectively (p=0.062 for the difference). The combination of the two biomarkers improved discrimination over NT-proBNP alone (p=0.011), but not over hs-cTnT (p=0.470) (Figure). A NT-proBNP level &lt;600 ng/L or a hs-cTnT level &lt;17 ng/L were optimal for ruling out amyloidosis, with a negative predictive value of 95% in both cases. Patients with AL amyloidosis had higher NT-proBNP and hs-cTnT than those with ATTR (10809 ng/L [6292–17483] vs. 3084 [1841–7624], p=0.014; 130 ng/L [64–211] vs. 61 [48–95], p=0.006). The difference was even more prominent when biomarker levels were normalized for LV mass (NT-proBNP/LV mass, 33.9 ng/L/g [20.4–53.8] vs. 10.0 [5.8–23.5], p=0.002; hs-cTnT/LV mass, 0.48 ng/L/g [0.25–0.71] vs. 0.19 [0.14–0.26], p=0.001). NT-proBNP and hs-cTnT could effectively discriminate patients with AL amyloidosis among subjects with clinical suspicion of CA (AUC values of 0.787 and 0.805 respectively) (Figure). Figure 1 Conclusions Plasma NT-proBNP and hs-cTnT have diagnostic value in patients with suspected CA. In the subgroup with CA, both biomarkers are higher in patients with AL amyloidosis even when normalizing for LV mass, possibly because of a greater cardiotoxic effect of light-chain fibrils.

Adefovir Dipivoxil-induced Fanconi's Syndrome and Osteomalacia Following Multiple Bone Fractures in a Patient with Chronic Hepatitis B

We herein present the case of a 66-year-old Japanese man with Fanconi's syndrome. He had been receiving adefovir dipivoxil (ADV) for the treatment of entecavir (ETV)-resistant chronic hepatitis B (CHB) for four years in his 8-year treatment of hepatocellular carcinoma (HCC), but was referred to our hospital after increased levels of bone pain in his ribs, knees, and ankles. Renal dysfunction, hypophosphatemia, and increased levels of bone alkaline phosphatase were found by a hematology test after admission for treatment of HCC. Radiography and 99m Tc-labeled hydroxymethylene diphosphonate (HMDP) scintigraphy revealed multiple insufficiency fractures in the ribs, knees, ankles, and heels. After switching from ADV to tenofovir disoproxil fumarate (TDF) and treatment with calcitriol and sodium dihydrogenphosphate, the patient's serum phosphate levels slightly increased and renal dysfunction did not improve, but after six months his clinical symptoms disappeared. To detect and prevent adverse effects from ADV, physicians and pharmacists should carefully monitor renal function and serum phosphate levels in patients with hepatitis B virus (HBV) treated for a long time with ADV.

Tc-99m hydroxymethylene diphosphonate scintigraphy, computed tomography, and magnetic resonance imaging of osteonecrosis in the mandible: Osteoradionecrosis versus medication-related osteonecrosis of the jaw.

PurposeTo present characteristic findings of Tc-99m hydroxymethylene diphosphonate (HMDP) scintigraphy, computed tomography (CT), and magnetic resonance (MR) imaging for osteonecrosis in the mandible, especially osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ).Materials and MethodsThirteen patients with MRONJ and 7 patients with ORN in the mandible underwent Tc-99m HMDP scintigraphy, CT, and MR imaging (T1-weighted images [T1WI], T2-weighted images [T2WI], short inversion time inversion recovery images [STIR]), diffusion-weighted images [DWI], and apparent diffusion coefficient [ADC] mapping). The associations of scintigraphy, CT, and MR imaging findings with MRONJ and ORN were analyzed using the chi-square test with the Pearson exact test.ResultsThirteen patients with MRONJ and 7 patients with ORN in the mandible showed low signal intensity on T1WI and ADC mapping, high signal intensity on STIR and DWI, and increased uptake on scintigraphy. Periosteal bone proliferation on CT was observed in 69.2% of patients with MRONJ (9 of 13) versus 14.3% of patients with ORN (1 of 7) (P=0.019).ConclusionThis study presented characteristic imaging findings of MRONJ and ORN on scintigraphy, CT, and MR imaging. Our results suggest that CT can be effective for detecting MRONJ and ORN.

Imaging cardiac innervation in hereditary transthyretin (ATTRm) amyloidosis: A marker for neuropathy or cardiomyopathy in case of heart failure?

BackgroundNuclear imaging modalities using 123Iodine-metaiodobenzylguanidine (123I-MIBG) and bone seeking tracers identify early cardiac involvement in ATTRm amyloidosis patients. However, little is known whether results from 123I-MIBG scintigraphy actually correlate to markers for either cardiac autonomic neuropathy or cardiomyopathy. MethodsAll TTR mutation carriers and ATTRm patients who underwent both 123I-MIBG and 99mTechnetium-hydroxymethylene diphosphonate (99mTc-HDP) scintigraphy were included. Cardiomyopathy was defined as NT-proBNP > 365 ng/L, and cardiac autonomic neuropathy as abnormal cardiovascular reflexes at autonomic function tests. Late 123I-MIBG heart-to-mediastinum ratio (HMR) < 2.0 or wash-out > 20%, and any cardiac 99mTc-HDP uptake were considered as abnormal. Results39 patients (13 carriers and 26 ATTRm patients) were included in this study. Patients with cardiomyopathy, with or without cardiac autonomic neuropathy, had lower late HMR than similar patients without cardiomyopathy [median 1.1 (range 1.0-1.5) and 1.5(1.2-2.6) vs 2.4 (1.4-3.8) and 2.5 (1.5-3.7), respectively, P < 0.001]. Late HMR and wash-out (inversely) correlated with NT-proBNP r = − 0.652 (P < 0.001) and r = 0.756 (P < 0.001), respectively. Furthermore, late HMR and wash-out (inversely) correlated with cardiac 99mTc-HDP uptake r = − 0.663 (P < 0.001) and r = 0.617 (P < 0.001), respectively. ConclusionIn case of heart failure, 123I-MIBG scintigraphy reflects cardiomyopathy rather than cardiac autonomic neuropathy in ATTRm patients and TTR mutation carriers. 123I-MIBG scintigraphy may already be abnormal before any cardiac bone tracer uptake is visible.

Cardiac denervation evidenced by MIBG occurs earlier than amyloid deposits detection by diphosphonate scintigraphy in TTR mutation carriers.

Cardiac involvement in familial transthyretin (TTR) amyloidosis is of major prognostic value, and the development of early-diagnostic tools that could trigger the use of new disease-modifying treatments is crucial. The aim of our study was to compare the respective contributions of 99mTc-diphosphonate scintigraphy (DPD, detecting amyloid deposits) and 123I-MIBG (MIBG, assessing cardiac sympathetic denervation) in patients with genetically proven TTR mutation referred for the assessment of cardiac involvement. We prospectively studied 75 consecutive patients (classified as symptomatic or asymptomatic carriers), using clinical evaluation, biomarkers (troponin and BNP), echocardiography, and nuclear imaging. Patients were classified as having normal heart-to-mediastinum (HMR) MIBG uptake ratio 4h after injection (defined by HM4 ≥ 1.85) or abnormal HM4 < 1.85, and positive DPD uptake (grade ≥ 1 of Perugini classification) or negative DPD uptake. Among 75 patients, 49 (65%) presented with scintigraphic sympathetic cardiac denervation and 29 (39%) with myocardial diphosphonate uptake. When MIBG was normal, DPD was negative except for two patients. Age was an independent predictor of abnormal scintigraphic result of both MIBG and DPD (HR 1.08 and 1.15 respectively), whereas echocardiographic-derived indicators of increased left ventricular filling pressure (E/e' ratio) was an independent predictor of abnormal MIBG (HR 1.33) and global longitudinal strain of positive DPD (HR 1.45). In asymptomatic patients (n = 31), MIBG was abnormal in 48% (n = 15) among whom 50% had a normal DPD; all those with a normal MIBG (n = 16) had a normal DPD. In TTR mutation carriers, cardiac sympathetic denervation evidenced by decreased MIBG uptake is detected earlier than amyloid burden evidenced by DPD. These results raise the possibility of a diagnostic role for MIBG scintigraphy at an early stage of cardiac involvement in TTR-mutated carriers, in addition to its well-established prognostic value.

Lung uptake during 99mTc-hydroxymethylene diphosphonate scintigraphy in patient with TTR cardiac amyloidosis: An underestimated phenomenon

BackgroundFull body scintigraphy using bone tracers plays an important role in defining the type of amyloidosis and in diagnosing the heart involvement (cardiac amyloidosis, CA). No study has been conducted to explore lung retention (LR) in CA and its correlation to heart retention (HR).We evaluated LR in patients undergoing 99mTc-HMDP scintigraphy during evaluation for suspected CA. Methods and resultsWe enrolled 93 suspected CA patients. Patients underwent a complete diagnostic work up. After diagnostic process 82 patients resulted affected by certain CA (20 AL and 62 TTR), while 11 subjects showed left ventricular hypertrophy (LVH) not caused by CA. 99mTc-HMDP cardiac uptake was evaluated using the Perugini visual score while the modified Janssen score was used for LR estimation (grade 0 no uptake, grade 1 less than ribs, grade 2 more than ribs). Results99mTc-HMDP LR was observed in 1/20 AL patient (5%), while 36/62 (58%) TTR patients showed LR with 29 grade 1 (47%) and 7 grade 2 (11%). No LR was observed in patients with LVH and no CA. LR was not evident in patients without HR, present in 1/3 (33%) of the patients with Perugini 1 HR and 11/24 (46%) and 26/36 (72%) of the patients showing respectively a Perugini 2 and a Perugini 3. Conclusion99mTc-HMDP scintigraphy shows LR in about 60% of TTR subjects, related to the grade of HR. In AL amyloidosis LR is less frequent than in TTR amyloidosis suggesting an aetiological tropism that seems comparable to the already known TTR related cardiac tropism.

Coexistent Superscan and Lincoln Sign on Bone Scintigraphy

A 70-year-old man underwent Tc-methylene diphosphonate scintigraphy for staging of adenocarcinoma prostate. Scintigraphy revealed diffuse increased tracer uptake in skeletal system along with faint renal visualization, a pattern compatible with metastatic superscan. The scintigraphy also revealed increased radiotracer uptake in the body of the mandible-Lincoln sign or black beard sign. Radiological imaging revealed sclerotic lesions throughout the skeleton including the mandible, confirming widespread skeletal metastases. Lincoln sign is previously described in monostotic Paget disease of the mandible and in contiguous spread of oral malignancy. We describe this pattern in distant metastatic involvement from carcinoma prostate with coexistent superscan pattern.

Accuracy of 99mTc-Hydroxymethylene diphosphonate scintigraphy for diagnosis of transthyretin cardiac amyloidosis

Background and AimEither 99mTechnetium diphosphonate (Tc-DPD) or pyrophosphate (Tc-PYP) scintigraphy plays a relevant role in diagnosing transthyretin cardiac amyloidosis (CA), and labeled radiotracers have been extensively studied in diagnosing CA. Few studies have analyzed and validated 99mTc-Hydroxymethylene diphosphonate (Tc-HMDP). Our aim was to validate the diagnostic accuracy of Tc-HMDP total-body scintigraphy in a cohort of patients with biopsy-proven transthyretin CA. Methods and ResultsWe retrospectively evaluated all patients undergoing 99mTc-HMDP total-body scintigraphy, in adjunct to a comprehensive diagnostic work-up for suspected CA. Sixty-five patients were finally diagnosed with CA, while it was excluded in 20 subjects with left ventricular hypertrophy of various etiologies. Twenty-six patients had AL-CA, 39 had TTR CA (16 TTRm, 23 TTRwt). At Tc-HMDP scintigraphy, 2 AL patients showed a Perugini score grade 1 heart uptake, while 24 showed no uptake. All TTR patients showed Tc-HMDP uptake, with three patients showing a Perugini score grade 1, 16 grade 2, and 20 grade 3, respectively. No uptake was observed in patients with left ventricular hypertrophy. A positive Tc-HMDP scintigraphy showed a 100% sensitivity and a 96% specificity for TTR CA identification. ConclusionsTc-HMDP scintigraphy is as accurate as Tc-DPD or Tc-PYP, and may therefore de facto be considered a valuable tool for the diagnosis of TTR CA.