Hydroxymethylene Diphosphonate Research Articles

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.

Equine skeletal scintigraphy: Comparing lesion detection ability of methylene diphosphonate and hydroxymethylene diphosphonate in the caudal cervical and proximal metacarpal/metatarsal regions.

Data regarding the lesion detection ability of different radiotracers are lacking in equine bone scintigraphy. In this prospective study, hydroxymethylene diphosphonate (HMDP) and methylene diphosphonate (MDP) were compared in horses with increased radiopharmaceutical uptake either in the caudal cervical region (CS group) or in the proximal metacarpal/metatarsal region (PMR group). Region of interest analysis was used to determine normal bone-to-soft tissue ratios, lesion-to-normal bone ratios and lesion-to-soft tissue ratios. Qualitative scoring and total count rates were recorded for each image. A total of 213 scintigrams were included. Within the PMR group, there were significantly higher lesion-to-normal bone ratios for MDP compared with HMDP (p=0.02). In the CS group, normal bone-to-soft tissue ratios were significantly higher for HMDP (p=0.01). The interobserver agreement with regard to the qualitative assessment of the scintigrams was poor. Paired studies, comparing the different radiotracers in the same patient, were not feasible. This study revealed minor differences between the two radiotracers, although thesehave no practical implications. Both radiopharmaceuticals are well suited for detecting lesions at the investigated sites using equine bone scintigraphy.

Stability of standardized uptake values for quantitative bone SPECT for jawbone lesions: a single-center cross-sectional study

BackgroundThe long time required for bone uptake of radiopharmaceutical material after injection for bone scintigraphy is a burden for patients with poor health. Thus, to assess whether the uptake time could be reduced for single-photon emission computed tomography (SPECT) of the jawbone, this study evaluated differences in maximum standardized uptake values (SUVmax) within patients using SPECT imaging at 2 and 3 hours after radiopharmaceutical injection.MethodsA total of 33 patients undergoing treatment or in post-treatment follow-up for medication-related osteonecrosis of the jaw, who visited our hospital between July 2020 and August 2021 and could receive SPECT twice on the same day, were enrolled in the study. Patients were injected with technetium-99 m hydroxymethylene diphosphonate (Tc-99 m HMDP) intravenously. The SUVmax for healthy parietal bones and jawbone lesions were calculated from the SPECT images using quantitative analysis software, and the SUVmax were compared between 2- and 3-hour uptake times.ResultsAfter exclusion, 30 patients were included in the study. In the 2-hour and 3-hour images, the median SUVmax of the parietal bones were 1.90 and 1.81, respectively, and those of the jawbone lesions were 9.25 and 9.39, respectively. The limits of agreement (LOA) ranged from − 0.33 to 0.25 in the parietal bones, and the %LOA ranged from − 9.8 to 17.3% in the jawbone lesions, showing high equivalence between the two uptake durations. The SUVmax showed no clinical differences between the 2- and 3-hour uptake durations for Tc-99 m HMDP SPECT of the jawbone.ConclusionsThe results of this study justify a 2–3-hour uptake window when performing quantitative SPECT of the jawbone. Therefore, the minimum uptake time can potentially be reduced to only 2 hours.

Clinical and Prognostic Implications of Right Ventricular Uptake on Bone Scintigraphy in Transthyretin Amyloid Cardiomyopathy.

The extent of myocardial bone tracer uptake with technetium pyrophosphate, hydroxymethylene diphosphonate, and 3,3-diphosphono-1,2-propanodicarboxylate in transthyretin amyloid cardiomyopathy (ATTR-CM) might reflect cardiac amyloid burden and be associated with outcome. Consecutive patients with ATTR-CM who underwent diagnostic bone tracer scintigraphy with acquisition of whole-body planar and cardiac single-photon emission computed tomography (SPECT) images from the National Amyloidosis Centre and 4 Italian centers were included. Cardiac uptake was defined according to the Perugini classification: 0=absent cardiac uptake; 1=mild uptake less than bone; 2=moderate uptake equal to bone; and 3=high uptake greater than bone. Extent of right ventricular (RV) uptake was defined as focal (basal segment of the RV free wall only) or diffuse (extending beyond basal segment) on the basis of SPECT imaging. The primary outcome was all-cause mortality. Among 1422 patients with ATTR-CM, RV uptake accompanying left ventricular uptake was identified by SPECT imaging in 100% of cases at diagnosis. Median follow-up in the whole cohort was 34 months (interquartile range, 21 to 50 months), and 494 patients died. By Kaplan-Meier analysis, diffuse RV uptake on SPECT imaging (n=936) was associated with higher all-cause mortality compared with focal (n=486) RV uptake (77.9% versus 22.1%; P<0.001), whereas Perugini grade was not associated with survival (P=0.27 in grade 2 versus grade 3). On multivariable analysis, after adjustment for age at diagnosis (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04]; P<0.001), presence of the p.(V142I) TTR variant (HR, 1.42 [95% CI, 1.20-1.81]; P=0.004), National Amyloidosis Centre stage (each category, P<0.001), stroke volume index (HR, 0.99 [95% CI, 0.97-0.99]; P=0.043), E/e' (HR, 1.02 [95% CI, 1.007-1.03]; P=0.004), right atrial area index (HR, 1.05 [95% CI, 1.02-1.08]; P=0.001), and left ventricular global longitudinal strain (HR, 1.06 [95% CI, 1.03-1.09]; P<0.001), diffuse RV uptake on SPECT imaging (HR, 1.60 [95% CI, 1.26-2.04]; P<0.001) remained an independent predictor of all-cause mortality. The prognostic value of diffuse RV uptake was maintained across each National Amyloidosis Centre stage and in both wild-type and hereditary ATTR-CM (P<0.001 and P=0.02, respectively). Diffuse RV uptake of bone tracer on SPECT imaging is associated with poor outcomes in patients with ATTR-CM and is an independent prognostic marker at diagnosis.

Lights and Shadows of Clinical Applications of Cardiac Scintigraphy with Bone Tracers in Suspected Amyloidosis.

Radionuclide bone scintigraphy is the cornerstone of an imaging-based algorithm for accurate non-invasive diagnosis of transthyretin cardiac amyloidosis (ATTR-CA). In patients with heart failure and suggestive echocardiographic and/or cardiac magnetic resonance imaging findings, the positive predictive value of Perugini grade 2 or 3 myocardial uptake on a radionuclide bone scan approaches 100% for the diagnosis of ATTR-CA as long as there is no biochemical evidence of a clonal dyscrasia. The technetium-labelled tracers that are currently validated for non-invasive diagnosis of ATTR-CA include pyrophosphate (99mTc-PYP); hydroxymethylene diphosphonate (99mTc-HMDP); and 3,3-diphosphono-1,2-propanodicarboxylate (99mTc-DPD). Although nuclear scintigraphy has transformed the contemporary diagnostic approach to ATTR-CA, a number of grey areas remains, including the mechanism for binding tracers to the infiltrated heart, differences in the kinetics and distribution of these radiotracers, differences in protocols of image acquisition worldwide, the clinical significance of extra-cardiac uptake, and the use of this technique for prognostic stratification, monitoring disease progression and assessing the response to disease-modifying treatments. This review will deal with the most relevant unmet needs and clinical questions concerning scintigraphy with bone tracers in ATTR-CA, providing expert opinions on possible future developments in the clinical application of these radiotracers in order to offer practical information for the interpretation of nuclear images by physicians involved in the care of patients with this ATTR-CA.

Dynamic blood flow imaging with 99mTc-hydroxymethylene diphosphonate as a therapeutic response marker in patients with Raynaud's phenomenon.

We evaluated the predictive value of dynamic blood flow scintigraphy with 99mTc-HDP (hydroxymethylene diphosphonate) for therapeutic response in patients with Raynaud's phenomenon (RP). Eighty patients who underwent dynamic blood flow scintigraphy using the one-hand chilling method were enrolled. We analyzed the quantitative variables as the ratio of chilled fingers to ambient fingers (CAfinger), that of the chilled hand to ambient hand (CAhand), and that of chilled fingers to ambient palm (FPR) (CAFPR) at 15 and 30s after 99mTc-HDP bolus injection. Total cumulative radioactivity counts for 180s were obtained. We evaluated the clinical utility of these quantitative parameters with other clinical variables, including RP severity, therapeutic compliance, types of RP, and scintigraphic interpretation of findings in patients with RP. Fifty-two patients showed poor therapeutic response. There were significant differences between good- and poor-therapeutic responder groups in RP intensity (p = 0.003), CAfinger15s (p = 0.008), CAfinger30s (p = 0.002), CAfinger180s (p = 0.011), CAhand15s (p = 0.008), CAhand30s (p = 0.007), CAhand180s (p = 0.017), CAFPR30s (p = 0.004), and CAFPR180s (p = 0.002). After multivariate logistic regression analysis, only CAfinger30s (p = 0.002) had an independent predictive value of the therapeutic response. 99mTc-HDP dynamic blood flow scintigraphy could be helpful in predicting the therapeutic response in patients with RP.

Estimated population prevalence of cardiac transthyretin amyloidosis as an incidental finding on bone scintigraphy in a university hospital in Colombia

Abstract Background Cardiac uptake in bone scintigraphy is highly sensitive and specific for transthyretin cardiac amyloidosis (ATTR), allowing a useful noninvasive diagnostic pathway even before echocardiographic or electrocardiographic abnormalities are present. Early diagnosis translates into early treatment and, thus, improves morbidity and mortality. In Colombia, ATTR diagnosis is still delayed or missed, and no studies have described incidental cardiac uptake on bone scintigraphy. Regarding health resources, the economic impact derived from the treatment of CA in Latam requires rigorous patient selection. This study aims to bridge this gap and improve the local clinical context. Methods We performed a retrospective cohort study which included all patients older than 65 who underwent bone scintigraphy using 99m Technetium labeled hydroxy-methylene- diphosphonate (HMDP) between January 2020 to December 2022 at our institution. Two independent physicians screened the bone scans, which a Nuclear Imaging specialist following the American Society of Nuclear Radiology guidelines then graded. Bone scans indicated for suspicion of ATTR were excluded. The prevalence of cardiac uptake and demographic characteristics were assessed. Results A total of 1206 patients were analyzed. Thirty-eight were excluded due to suspected CA. The study population, therefore, consisted of n=1168 patients with musculoskeletal (58%) and oncologic (40%) indications for scintigraphy. 55% of the sample were men; the median age was 75. Cardiac uptake was found in 1.5% of patients, from which 28% had Grade Perugini 1, 17% had Grade Perugini 2, and 56% had Grade Perugini 3. Among patients with incidental uptake, 78% were men, with a median age of 84 years; 17% had heart failure, 11% had aortic stenosis, 11% had dysautonomia, 6% had polyneuropathy, 22% had spinal stenosis, and 17% had carpal tunnel syndrome. Conclusion We describe the first South American cohort of incidental cardiac uptake in HMDP scintigraphy. The observed incidence in this cohort was 1.5%, in concordance with previously published data in other continents. Bone scintigraphy is highly available in all regions of Colombia, allowing the identification of subclinical ATTR before severe functional impairment occurs and prompt treatment initiation in CA patients. The development of reference centers for the healthcare of CA patients allows the incorporation of clinical pathways that facilitate the approach of patients with incidental myocardial uptake in bone scans requested for non-cardiac causes, which warrant further clinical assessment and follow-up.Clinical characteristicsIncidental cardiac uptake

Radiopharmaceutical extravasation in bone scintigraphy: a cross-sectional study.

Tc-99m Hydroxymethylene diphosphonate (HMDP) bone scintigraphy is commonly used to diagnose bone disorders. We aimed to quantify and characterize the occurrence of radiopharmaceutical extravasation in bone scintigraphy, using Tc-99m HMDP, as well as to compare the visual classification of the events with an independent analysis using image processing software. We conducted a cross-sectional study, using data from a total of 400 (9.1%) exams, randomly selected from all the procedures performed in 2018 in the Portuguese Institute of Oncology of Porto, Portugal. Prevalence estimate and the corresponding 95% confidence interval (CI) was computed for the presence of extravasation. Odds ratios and 95% CI were computed to quantify the association between demographic and clinical characteristics, and the occurrence of extravasation. The prevalence of Tc-99m HMDP extravasation was 26.5% (95% CI: 22.4-31.0). Those from an inpatient setting had almost seven-fold higher odds of extravasation than those from an outpatient setting. When the wrist was used for administration, there was three times more odds of extravasation when compared to the use of hand. There were statistically significant differences in the median scores of extravasations severity obtained from image processing software according to the different grades attributed by visual appreciation ( P < 0.001). Tc-99m HMDP extravasation occurred in one out of four patients, being more frequent among those from an inpatient setting and when the wrist was used for administration. Visual appreciation of the extravasation seems to be acceptable to classify its severity.

A computer program to assess the bone scan index for Tc-99m hydroxymethylene diphosphonate: evaluation of jaw pathologies of patients with bone metastases using SPECT/CT

This study aimed to evaluate the jaw pathologies of patients with bone metastases using a computer program to assess the bone scan index (BSI) for Tc-99m hydroxymethylene diphosphonate (HMDP) with single-photon emission computed tomography/computed tomography (SPECT/CT). Ninety-seven patients with jaw pathologies (24 with bone metastases and 73 without) were evaluated. High-risk hot spots and BSI in the patients were evaluated using the VSBONE BSI (ver.1.1) analysis software for Tc-99m HMDP that scanned SPECT/CT and automatically defined the data. The two groups were compared using the Pearson chi-square test and Mann-Whitney U test for high-risk hot spots and BSI, respectively. A P value of <0.05 was considered statistically significant. High-risk hot spot occurrence was significantly correlated to bone metastases [sensitivity, 21/24 (87.5%); specificity, 40/73 (54.8%); accuracy, 61/97 (62.9%); P < 0.001]. The number of high-risk hot spots was higher in patients with bone metastases (5.96 ± 10.30) than in those without (0.90 ± 1.50; P < 0.001). Furthermore, the BSI for patients with bone metastases (1.44 ± 2.18%) was significantly higher than for those without (0.22 ± 0.44%; P < 0.001). A computer program that assessed BSI for Tc-99m HMDP may be useful in the evaluation of patients with bone metastases using SPECT/CT.

Applying Pix2pix to Translate Hyperemia in Blood Pool Image into Corresponding Increased Bone Uptake in Delayed Image in Three-Phase Bone Scintigraphy.

Delayed images may not be acquired due to severe pain, drowsiness, or worsening vital signs while waiting after blood pool imaging in three-phase bone scintigraphy. If the hyperemia in the blood pool image contains information from which increased uptake on the delayed images can be inferred, the generative adversarial network (GAN) can generate the increased uptake from the hyperemia. We attempted to apply pix2pix, a type of conditional GAN, to transform hyperemia into increased bone uptake. We enrolled 1464 patients who underwent three-phase bone scintigraphy for inflammatory arthritis, osteomyelitis, complex regional pain syndrome (CRPS), cellulitis, and recent bone injury. Blood pool images were acquired 10min after intravenous injection of Tc-99m hydroxymethylene diphosphonate, and delayed bone images were obtained after 3h. The model was based on the open-source code of the pix2pix model with perceptual loss. Increased uptake in the delayed images generated by the model was evaluated using lesion-based analysis by a nuclear radiologist in areas consistent with hyperemia in the blood pool images. The model showed sensitivities of 77.8% and 87.5% for inflammatory arthritis and CRPS, respectively. In osteomyelitis and cellulitis, their sensitivities of about 44% were observed. However, in cases of recent bone injury, the sensitivity was only 6.3% in areas consistent with focal hyperemia. The model based on pix2pix generated increased uptake in delayed images matching the hyperemia in the blood pool image in inflammatory arthritis and CRPS.

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.

99mTc Bone-Avid Tracer Cardiac Scintigraphy: Role in Noninvasive Diagnosis of Transthyretin Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is an overlooked cause of heart failure, with substantial morbidity and mortality. The emergence of several novel therapies has fueled the interest in early and accurate diagnosis of ATTR-CA so that potentially life-saving pharmacologic therapy can be administered in a timely manner. The most promising imaging modality and biomarker is SPECT imaging with technetium 99m (99mTc)-radiolabeled bone-seeking tracers, which have high specificity in the diagnosis of ATTR-CA, potentially obviating biopsy. In this article, the authors provide a focused review on the use of 99mTc pyrophosphate (PYP), 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), and hydroxymethylene diphosphonate (HMDP) for diagnosis of ATTR-CA, present a systematic approach to interpretation of the scans, and highlight several common pitfalls to illustrate important diagnostic principles for accurate interpretation of these images. The authors indicate when to use endomyocardial biopsy for the diagnosis of cardiac amyloidosis and conclude with a section on quantitation of 99mTc-PYP/DPD/HMDP imaging.

Comparison of maximum and mean standardized uptake values of jaw pathologies with bone SPECT/CT: an especial focus on medication-related osteonecrosis of the jaw.

To investigate the comparison of maximum and mean standardized uptake values (SUVs) of jaw pathologies with bone Single-photon emission computed tomography/computed tomography (SPECT/CT), and a special focus on medication-related osteonecrosis of the jaw (MRONJ). Eighty-nine patients with jaw pathologies (63 MRONJ, 13 chronic osteomyelitis, 11 osteoradionecrosis and 2 primary intraosseous carcinoma) underwent bone SPECT/CT scans acquisition at 4 h after intravenous injection of Tc-99m hydroxymethylene diphosphonate in this prospective study. The evaluation of mean and maximum SUVs of jaw pathologies were performed using Q. Metrix and Xeleris workstation and defined the data automatically. Statistical analyses were performed by Pearson's correlation coefficient for comparison of maximum and mean SUVs and Mann-Whitney U-test for SUVs of MRONJ. A P value lower than 0.05 was considered to indicate statistical significance. Maximum SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 17.6 ± 8.4, 21.7 ± 7.1, 11.9 ± 4.8 and 26.6 ± 7.0, respectively. Mean SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 10.1 ± 4.9, 11.9 ± 3.3, 7.0 ± 2.8 and 10.1 ± 4.5, respectively. The maximum SUV of jaw pathologies was significantly correlated with the mean SUV (Y = 0.494X + 1.228; R2 = 0.786; P < 0.001). Furthermore, maximum and mean SUVs of MRONJ had significant differences in underlying diseases, medication and staging. The maximum and mean SUVs with bone SPECT/CT can be an effective tool for the quantitative evaluation of jaw pathologies, especially MRONJ.

Clinical Usefulness of SPECT/CT for Assessing Postoperative Outcomes After Medial Opening-Wedge High Tibial Osteotomy.

Background:Qualitative studies have explored changes in Tc-99m hydroxymethylene diphosphonate (HDP) uptake on single-photon emission computed tomography and computed tomography (SPECT/CT) as a result of offloading after medial opening-wedge high tibial osteotomy (MOWHTO) in patients with medial compartment knee osteoarthritis. However, whether changes in the Tc-99m HDP uptake on SPECT/CT reflect the degree of clinical improvement in postoperative outcomes, especially when using minimal clinically important differences (MCIDs), has not been investigated.Purpose:To investigate the association between changes in Tc-99m HDP uptake on SPECT/CT and MCID-based improvement on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score in patients who underwent MOWHTO.Study Design:Cross-sectional study; Level of evidence, 3.Methods:The study included 35 knees in 31 patients who underwent MOWHTO. SPECT/CT was performed preoperatively and 3 years postoperatively with clinical and radiological assessments. On SPECT/CT, the knee joint was divided into 10 regions, and the radiotracer uptake amount of each region was divided by the uptake amount of the reference zone. Patients were divided into 2 groups based on whether they achieved the MCID of 16.1 points on the WOMAC at 3 years postoperatively, and changes in uptake amount on SPECT/CT were compared between the groups.Results:At 3 years postoperatively, 22 patients achieved the MCID on the WOMAC (62.9%; above-MCID group) and 13 patients did not (37.1%; below-MCID group). In the above-MCID group, significant improvement was observed in the WOMAC after MOWHTO (from 55.8 to 19.6; P < .05); however, significant improvement was not observed in the below-MCID group (from 38.8 to 32.3; P = .100). Based on mean change of uptake on SPECT/CT in each region, the above-MCID group showed significantly greater reduction of uptake on SPECT/CT than the below-MCID group in the femoral anteromedial compartment (P = .004), tibial anteromedial compartment (P = .009), and tibial anterolateral compartment (P = .031).Conclusion:Reduction in radiotracer uptake on SPECT/CT of the knee joint reflected clinical improvement in patient-reported outcomes following MOWHTO.

Mechanism of bisphosphonate-related osteonecrosis of the jaw (BRONJ) revealed by targeted removal of legacy bisphosphonate from jawbone using competing inert hydroxymethylene diphosphonate.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) presents as a morbid jawbone lesion in patients exposed to a nitrogen-containing bisphosphonate (N-BP). Although it is rare, BRONJ has caused apprehension among patients and healthcare providers and decreased acceptance of this antiresorptive drug class to treat osteoporosis and metastatic osteolysis. We report here a novel method to elucidate the pathological mechanism of BRONJ by the selective removal of legacy N-BP from the jawbone using an intra-oral application of hydroxymethylene diphosphonate (HMDP) formulated in liposome-based deformable nanoscale vesicles (DNV). After maxillary tooth extraction, zoledronate-treated mice developed delayed gingival wound closure, delayed tooth extraction socket healing and increased jawbone osteonecrosis consistent with human BRONJ lesions. Single cell RNA sequencing of mouse gingival cells revealed oral barrier immune dysregulation and unresolved proinflammatory reaction. HMDP-DNV topical applications to nascent mouse BRONJ lesions resulted in accelerated gingival wound closure and bone socket healing as well as attenuation of osteonecrosis development. The gingival single cell RNA sequencing demonstrated resolution of chronic inflammation by increased anti-inflammatory signature gene expression of lymphocytes and myeloid-derived suppressor cells. This study suggests that BRONJ pathology is related to N-BP levels in jawbones and demonstrates the potential of HMDP-DNV as an effective BRONJ therapy.

Equine skeletal scintigraphy: Comparing normal bone-to-soft tissue ratio 2 and 4 hours after injection with either hydroxymethylene diphosphonate ormethylene diphosphonate.

In equine skeletal scintigraphy, there is no information about the possible influence of different phosphonate compounds on image quality. This prospective randomised study determined bone uptake changes and image quality for hydroxymethylene diphosphonate (HDP) and methylene diphosphonate (MDP) in equine patients at different time points. Scintigraphic images of the radius and the tibia of 20 horses were acquired at 2 and 4 hours after injection of either technetium-labelled HDP or MDP. Three regions of interest were identified-in the bone diaphysis, adjacent soft tissue and background area-to determine the normal bone-to-soft tissue ratio (BSR). Qualitative analysis was performed using a modified scoring system. In terms of BSR and count rates, HDP showed a slightly better incorporation into bone compared to MDP, but significant differences were only detected for count rates at 4 hours after injection (p = 0.048). The radiopharmaceutical used did not influence qualitative image scoring, which was correlated with the BSR (ρ = 0.49; p ≤ 0.001). The choice of HDP or MDP for equine skeletal scintigraphy does not seem to substantially affect BSR and qualitative image scoring. Further studies with a larger sample size, including the evaluation of lesion detection ability for both bone-seeking agents, are needed.

Radiopharmaceutical Supply Disruptions and the Use of 99mTc-99 Hydroxymethylene Diphosphonate as an Alternative to 99mTc-Pyrophosphate for the Diagnosis of Transthyretin Cardiac Amyloidosis: An ASNC Information Statement

Radiopharmaceutical Supply Disruptions and the Use of 99mTc-99 Hydroxymethylene Diphosphonate as an Alternative to 99mTc-Pyrophosphate for the Diagnosis of Transthyretin Cardiac Amyloidosis: An ASNC Information Statement

Prognostic significance of incidental suspected transthyretin amyloidosis on routine bone scintigraphy

BackgroundTransthyretin amyloidosis (ATTR) is an occasional incidental finding on bone scintigraphy. We studied its prognostic impact in elderly patients. MethodsThe study population consisted of 2000 patients aged over 70 years who underwent bone scintigraphies with clinical indications in three nuclear medicine departments (Kymenlaakso, Jorvi and Meilahti hospitals) in Finland. All studies were performed using 99mTechnetium labeled hydroxymethylene diphosphonate (HMDP). ATTR was suspected in patients with ≥grade 2 Perugini grade uptake (grade 0-3). Heart-to-contralateral ratio (H/CL) of ≥ 1.30 was considered positive for ATTR. The overall and cardiovascular mortality were obtained from the Finnish National Statistical Service. ResultsThere were a total of 1014 deaths (51%) and 177 cardiovascular deaths (9%) during median follow-up of 4 ± 2 years. ATTR was suspected in 69 patients (3.6%) of which 54 (2.7%) had grade 2 and 15 (.8%) had grade 3 uptake and in 47 patients (2.4%) by H/CL ratio. In multivariate analyses age, bone metastasis, H/CL ratio and grade 3 uptake were independent predictors of overall and cardiovascular mortality. Grade 2 uptake was a predictor of cardiovascular mortality. ConclusionsA suspected ATTR as an incidental finding on bone scintigraphy predicts elevated overall and cardiovascular mortality in elderly patients.

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.

Abstract 233: A Network Meta-analysis Comparing The Performance Of Magnetic Resonance Imaging, Positron Emission Tomography And Bone Scintigraphy Techniques In Detecting Cardiac Amyloidosis

Aims: Diagnosing cardiac amyloidosis with non-invasive imaging studies can be challenging. We aims to systematically review the published literature and compare the performance of magnetic resonance (CMR), positron emission tomography (PET) and bone scintigraphy (BS) for diagnosis of cardiac amyloidosis. Methods: Medical electronic databases were searched for studies evaluating the diagnostic performance of CMR, PET or BS in diagnosing cardiac amyloidosis where histopathological examination of endomyocardial biopsy tissue or extra-cardiac organs were used as reference standards. We evaluated; CMR: extracellular volume (ECV), late gadolinium enhancement (LGE), T1 mapping; PET: F18-Amyloid, F18-Sodium Fluoride (NaF), and C11-PIB; BS: Technetium-99m (Tc) hydroxymethylene diphosphonate (Tc-HMDP), Tc-3,3-diphosphono-1,2-propanodicarboxylicacid (Tc-DPD), Tc- pyrophosphate (Tc-PYP). Methodological quality was assessed using a Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). To summarize sensitivity, specificity, and superiority, we used an arm-based hierarchical model which expresses the logit transformed sensitivity and specificity as the sum of fixed effects for test, correlated study-effects to model the inherent correlation between sensitivity and specificity and a random error associated with various tests evaluated in each study. Results: Of the 2871 studies identified, 39 studies met the inclusion criteria. Sensitivity and specificity and Superiority of the various imaging modalities in diagnosing cardiac amyloidosis were calculated (Figure). Study quality assessed by QUADAS-2 was generally good with negligible evidence of bias. Conclusion: Various non-invasive imaging modalities have been studied for diagnosing cardiac amyloidosis with varying sensitivity and specificity. Comparative studies may be warranted to improve non-invasive diagnostic algorithms of suspected cardiac amyloidosis.