99mTc-DPD Uptake Research Articles

DPD quantification correlates with ECV and disease severity in patients with ATTR-CM

Abstract Background The pathophysiological hallmark of transthyretin amyloid cardiomyopathy (ATTR-CM) is the deposition of amyloid within the myocardium. However, the association between myocardial amyloid load and quantitative cardiac 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) uptake is barely investigated. Purpose We aimed to investigate the relationship between quantitative cardiac 99mTc-DPD uptake and myocardial amyloid load, assessed by extracellular volume (ECV) on cardiac magnetic resonance (CMR) imaging, along with cardiac function in patients with ATTR-CM. Methods Forty ATTR-CM patients underwent 99mTc-DPD single-photon emission computed tomography/computed tomography (SPECT/CT) and CMR imaging. Results We observed significant correlations (r, Spearman's correlation coefficient) between the standardized uptake value (SUV) retention index and myocardial amyloid load (ECV: r=0.677, p<0.001; native T1 time: r=0.430, p=0.006), longitudinal cardiac function [right ventricular longitudinal strain (RV-LS): r=0.472, p=0.002], cardiac biomarkers (NT-proBNP: r=0.543, p<0.001; troponin T: r=0.401, p=0.011), exercise capacity [6-min walking distance (6MWD): r=-0.410, p=0.010] and disease stage [National Amyloidosis Centre (NAC) ATTR stage: r=0.479, p=0.002]. ATTR-CM patients were divided into two cohorts based on the median of the SUV retention index (low cardiac uptake: <5.19 mg/dL, n=20; high cardiac uptake: ≥5.19 mg/dL, n=20). We observed significant between-cohort differences in terms of ECV (p<0.001), native T1 time (p=0.011), RV-LS (p=0.007), NT-proBNP (p<0.001), troponin T (p=0.030), 6MWD (p=0.002) and NAC ATTR stage (I: p<0.001, II: p=0.030, III: p=0.021). Conclusions In ATTR-CM, quantitative cardiac 99mTc-DPD uptake correlates with myocardial amyloid load, longitudinal cardiac function, cardiac biomarkers, exercise capacity, and disease stage. DPD quantification may provide a valuable tool for quantifying and monitoring cardiac disease burden in affected individuals.Table.Baseline Characteristics.Figure.Correlations.

Reply: Recent Evidence on Cardiac 99mTc-DPD Uptake After Therapy with Tafamidis May Reveal the Road to an Ultra-Early Diagnosis in Patients with ATTR Amyloidosis.

Reply: Recent Evidence on Cardiac 99mTc-DPD Uptake After Therapy with Tafamidis May Reveal the Road to an Ultra-Early Diagnosis in Patients with ATTR Amyloidosis.

Correlation of 99mTc-DPD bone scintigraphy with histological amyloid load in patients with ATTR cardiac amyloidosis

Abstract Background The significance of measuring 99mTc-labelled-3,3-diphospono-1,2-propanodicarboxylic acid (99mTc-DPD) in transthyretin (ATTR) cardiac amyloidosis has not been adequately studied. This single-centre observational study evaluated the correlation between 99mTc-DPD scintigraphy and histological amyloid load in endomyocardial biopsy (EMB). Methods Twenty-eight patients with biopsy-proven ATTR amyloidosis and concomitantly available 99mTc-DPD scintigraphy were included. Visual Perugini scoring, and (semi-)quantitative analysis of cardiac 99mTc-DPD uptake by planar whole-body imaging and single photon emission computed tomography (SPECT/CT) using regions of interest (ROI) were performed. From this, heart-to-whole-body ratio (H/WB) and heart-to-contralateral-chest ratio (H/CL) were calculated. Histological amyloid load was quantified using two different staining methods. Results Increased cardiac tracer uptake was documented in all patients (planar: ROImean 129 ± 37 cps; SPECT/CT: ROImean 369 ± 142 cps). Histological amyloid load (19 ± 13 %) significantly correlated with Perugini score (r=0.69, p<0.001, Figure 1) as well as with cardiac 99mTc-DPD uptake (planar: r=0.64, p<0.001, Figure 2; H/WB: r=0.50, p=0.014; SPECT/CT: r=0.53, p=0.008; H/CL: r=0.43, p=0.037) (results are shown for correlations with Congo Red-staining). Conclusion In ATTR, cardiac 99mTc-DPD uptake significantly correlated with histological amyloid load in EMB. Further studies are needed to implement thresholds in cardiac 99mTc-DPD uptake measurements for risk stratification and guidance of therapy.

Intratumoral 99mTc-DPD Uptake on Bone Scintigraphy in a Patient With Invasive Micropapillary Breast Carcinoma: A Pathologic Review.

Invasive micropapillary carcinoma (IMPC) is a rare and aggressive subtype of breast cancer with a poorer prognosis due to high local recurrence and lymphovascular invasion. Interestingly, IMPC often does not show suspicious patterns of calcifications related to malignancy on mammography. Therefore, the lack of suspicious calcifications makes it difficult to detect breast cancer on mammography. With only nonspecific calcifications on mammography, we observed an unusual intratumoral 99mTc-DPD uptake on whole-body bone scintigraphy in an IMPC breast cancer patient during the initial staging workup, and its characteristics were compared with mammographic findings and the postoperative pathologic features.

Reduction in 99mTc-DPD myocardial uptake with therapy of ATTR cardiomyopathy

Aims: Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis. Methods and results: ATTRv-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0–12.0) of treatment with RNAi therapeutics (patisiran: n = 5, inotersen: n = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, p = .028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, p < .001) in ATTRwt-CM patients (historical control cohort: n = 40) at follow-up [9.0 months (IQR: 7.0–10.0)] without beneficial impact on cardiac function. Conclusions: RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial 99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM.

Correlation of 99mTc-DPD bone scintigraphy with histological amyloid load in patients with ATTR cardiac amyloidosis

Background The significance of measuring 99mTc-labelled-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in transthyretin (ATTR) cardiac amyloidosis has not been adequately studied. This single-centre observational study evaluated the correlation between 99mTc-DPD scintigraphy and histological amyloid load in endomyocardial biopsy (EMB). Methods Twenty-eight patients with biopsy-proven ATTR amyloidosis and concomitantly available 99mTc-DPD scintigraphy were included. Visual Perugini scoring, and (semi-)quantitative analysis of cardiac 99mTc-DPD uptake by planar whole-body imaging and single photon emission computed tomography (SPECT/CT) using regions of interest (ROI) were performed. From this, heart-to-whole-body ratio (H/WB) and heart-to-contralateral-chest ratio (H/CL) were calculated. The histological amyloid load was quantified using two different staining methods. Results Increased cardiac tracer uptake was documented in all patients (planar: ROImean 129 ± 37 cps; SPECT/CT: ROImean 369 ± 142 cps). Histological amyloid load (19 ± 13%) significantly correlated with Perugini score (r = 0.69, p < .001) as well as with cardiac 99mTc-DPD uptake (planar: r = 0.64, p < .001; H/WB: r = 0.50, p = .014; SPECT/CT: r = 0.53, p = .008; H/CL: r = 0.43, p = .037) (results are shown for correlations with Congo Red-staining). Conclusion In ATTR, cardiac 99mTc-DPD uptake significantly correlated with histological amyloid load in EMB. Further studies are needed to implement thresholds in cardiac 99mTc-DPD uptake measurements for risk stratification and guidance of therapy.

Regression of Myocardial 99mTc-DPD Uptake After Tafamidis Treatment of Cardiac Transthyretin Amyloidosis.

Cardiac transthyretin amyloidosis is an infiltrative cardiomyopathy with high mortality. To date, there are no specific biomarkers to directly assess disease activity and response to specific treatments. Our aim was to evaluate scintigraphic changes after treatment with the transthyretin stabilizer tafamidis. Methods: We included patients who had undergone 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy before tafamidis initiation and after at least 9 mo. Tracer activity was assessed visually and quantitatively as SUVmax Results: The study included 14 patients who were on tafamidis for 44 ± 14 mo. We observed regression of Perugini grade in 5 patients, unchanged grade in 9 patients, and regression of mean heart-to-contralateral-lung ratio (P = 0.015) and SUVmax (P = 0.005). There were no changes in N-terminal pro-B-type natriuretic peptide or echocardiographic measures. Conclusion: Treatment with tafamidis results in regression of myocardial 99mTc-DPD uptake. 99mTc-DPD scintigraphy may provide useful imaging biomarkers to assess response to treatment.

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

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

Correlation of Quantitative 99mTc DPD Scintigraphy With Echocardiographic Alterations in Left Atrial Parameters in Transthyretin Amyloidosis

Cardiac transthyretin amyloidosis (ATTR) patients have high rates of atrial arrhythmias. We evaluated echocardiographic structural and functional left atrial (LA) parameters and correlated these with technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) bone scintigraphy tracer uptake within the LA in ATTR patients. ATTR patients (wild-type, hereditary and asymptomatic transthyretin [TTR] variant carriers) who had undergone 99mTc-DPD and transthoracic echocardiogram (TTE) were selected. Quantitative 99mTc-DPD uptake analysis and echocardiographic evaluation of LA structural and functional parameters was performed. Forty (40) ATTR patients (wild-type n=17; hereditary ATTR and TTR variant carriers n=23; median age 68.8±22 years) were included. TTE parameters including indexed LA minimum (LAVmin) (r=0.66), and LA maximum volumes (LAVmax) (r=0.64), LA emptying fraction (LAEF) (r=-0.68), LA function index (LAFI) (r=-0.70) and reservoir strain (ƐR) (r=-0.70) (p<0.001 for all) demonstrated good correlation to LA tracer uptake. Normal LA volume (LAVmin and LAVmax) and function (LAEF, LAFI and ƐR) was observed in hereditary ATTR and TTR variant carriers without cardiac tracer uptake. The subgroup of ATTR patients with atrial fibrillation/flutter demonstrated increased LAVmin and LAVmax with further reduction in LA function (LAEF, LAFI and ƐR). Receiver operating characteristic curves demonstrated strong diagnostic accuracies for LA structural (LAVmin and LAVmax; area under the curve [AUC] of 0.83 and 0.84 respectively) and functional (LAEF, LAFI and ƐR; AUC 0.81, 0.88 and 0.85, respectively) parameters. Left atrial structural and functional parameters demonstrated good correlations with quantitative 99mTc-DPD tracer LA uptake. Echocardiography and 99mTc-DPD scintigraphy may have significant roles in identification and surveillance of ATTR patients likely to develop atrial arrhythmias.

99mTc-DPD myocardial uptake and regional longitudinal strain in aTTR amyloidosis cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND amyloid cardiomyopathy is characterized by a typical "apical sparing" pattern of systolic longitudinal strain (LS) as visualized by echocardiography. Strain is well preserved at the apex of the left ventricle (LV) with a gradient from apex to base and the greatest impairment in the basal segments. The reason of this distribution is not clear. It could be a function of different amount of amyloid deposition. SPECT images using Technetium 99m bone tracers have shown a distribution mimicking regional LS. PURPOSE to compare regional myocardial LS and myocardial distribution of 99m Technetium-DPD (99m Tc-DPD) uptake in patients affected by aTTR amyloidosis cardiomyopathy. METHODS between 2016-2021 70 patients referred to our Cardiology Unit with heart failure/shortness of breath on exertion and showing significant left ventricular hypertrophy at 2-D echocardiography underwent 99m Tc-DPD scintigraphy to test the presence of cardiac amyloid. Grade 2-3 myocardial uptake at 180 minutes in the absence of abnormalities in the analysis of serum free light chains and serum and urine protein electrophoresis with immunofixation was considered sufficient for the diagnosis of aTTR amyloidosis. When scintigraphy was positive a SPECT study was performed to obtain semi quantitative measurements of segmental myocardial uptake (expressed as % of total myocardial uptake). Regional mean count was calculated by using a 6 basal, 12 mid and 2 apical segmental model. All patients underwent standard and 2D speckle tracking echocardiography. Mean systolic LS was calculated for each of 18 segments and mean basal (6 segments), mean mid (6 segments) and mean apical (6 segments) LS was calculated. RESULTS 46/70 patients had a positive scan and fulfilled criteria for aTTR amyloidosis. 33/46 had SPECT analysis. Male/female ratio was 29/4, age = 80 ± 6 years; 9/33 aortic stenosis; 19/33 carpal tunnel; 25/33 wild-type aTTR (4/33 ongoing genetic test); LV mass-=228 ± 48 g/m2; RWT = 0,73 ± 0,14; EF= 53 ± 9; EF to GLS ratio= 5,6 ±1,8. ANOVA showed a significant difference between basal, mid and apical strain as well as between basal, mid and apical uptake (-5,5 ± 4,4; -9,6 ± 3,2; -15,9 ± 5,6; p &amp;lt; 0,001; 55 ± 14; 62 ± 10; 51 ± 11; p = 0,0019). Comparison between groups showed that mean LS at the apex was significantly lower compared to basal and mid mean LS (Bonferroni test, p &amp;lt; 0,001) (Fig 1). Apical myocardial uptake was significantly lower compared to mid segment but not to basal (Bonferroni test, p = 0,02, p = 0,6 respectively) (Fig 1). Spearman’s test showed a correlation between LS and myocardial 99m Tc-DPD uptake (p = 0,01, Rho = 0,24). CONCLUSIONS Our data show that in this group of patients with cardiac aTTR amyloidosis apical LS is significantly lower compared to basal and mid segments and apical myocardial 99m Tc-DPD uptake is significantly lower compared to mid segments; a correlation between myocardial 99m Tc-DPD uptake distribution and the degree of LS impairment is present. Abstract Figure.

373 Utility of the early phase of DPD scintigraphy in the diagnosis of correlated TT-R cardiac amyloidosis

Abstract Aims The importance of cardiac scan with phosphonate-based radiotracers in the diagnosis of cardiac amyloidosis is now well established. Standard imaging is performed 3 h after tracer injection with a planar view on the cardiac region. This study sought to evaluate the predictive role of early-phase myocardial uptake (10 min after injection) of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) compared compared with standard late acquisition, in patients with suspected hereditary transthyretin-related cardiac amyloidosis (TTR-CA). Methods and results Fifty five patients with suspected of TTR-CA with typical aspects of the relative apical sparing at two-dimensional speckle-tracking echocardiography, reported as a specific pattern for cardiac amyloidosis, were enrolled after having signed informed written consent. They have been subjected to a 99mTc-DPD cardiac scintigraphy with planar acquisition at 10 min and 3 h after tracer injection (13 Mbq/Kg). Patients with cardiac uptake on the planar images concluded the examination with a SPECT-CT (cardiac protocol) to assess the affected myocardial segments. On planar images the heart-to-mediastinum-ratio was measured. Subsequently, the diagnosis of amyloidosis has to be confirmed with morphologic examinations such as biopsy and genetic tests. Of the enrolled patients with clinical and echocardiographic aspect of TTR-CA, 22 were positive for cardiac amyloidosis. All of them showed tracer uptake in both early and late images. In patients with positive results, the early-phase showed a Heart-to-mediastinum-ratio &amp;gt;1.2. SPECT/CT showed involvement of almost two myocardial segments: in all patients the ventricular septum showed significant tracer uptake. Conclusions Our small group of patients showed that 99mTc-DPD myocardial uptake intensity on early-phase scintigraphy can be used to anticipate the results of late images in diagnosis of TTR cardiac amyloidosis.

Correlation Between Quantitative Uptake of 99mTC-DPD and Echocardiographic Parameters in Cardiac ATTR: A Novel Follow-Up Strategy.

Aims: There has been a paradigm shift in diagnosis of cardiac transthyretin amyloidosis (ATTR) with non-invasive techniques including technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) bone scintigraphy. We evaluated structural and functional biventricular alterations by transthoracic echocardiography (TTE) and determined the correlation with 99mTc-DPD tracer uptake in ATTR.Materials and Methods: ATTR patients (wild-type, hereditary or asymptomatic transthyretin [TTR] variant carriers) with 99mTc-DPD and TTE were selected; 99mTc-DPD uptake was analyzed quantitatively. TTE assessment of left ventricle (LV) and right ventricle (RV) parameters was performed.Results: Forty ATTR patients (wild-type n = 17; hereditary ATTR and TTR variant carriers n = 23; median age 68.8 ± 22 years) were included. TTE parameters displaying good correlation with 99mTc-DPD tracer uptake included LV average wall thickness (r = 0.837), LV indexed mass (LVMI; r = 0.802), RV wall thickness (r = 0.610), average e' (r = −0.830), E/e' ratio (r = 0.786), LV global longitudinal strain (GLS; r = 0.714) and RV GLS (r = 0.632; p < 0.001 for all). Hereditary ATTR and TTR variant carriers without cardiac tracer uptake had normal echocardiographic parameters. Receiver operating characteristic curves demonstrated strong diagnostic accuracies for structural (LV wall thickness, LVMI and RV wall thickness; area under the curve (AUC) of 0.96 for all) and functional (LV and RV GLS; AUC of 0.86 and 0.88, respectively) parameters.Conclusion: Good correlations between TTE biventricular structural and functional parameters were demonstrated with quantitative 99mTc-DPD uptake. Echocardiography may potentially assume a significant role in longitudinal follow-up for monitoring disease progression and for evaluating treatment response.

Quantitation vs visual assessment of 99mTc-DPD cardiac uptake in patients with suspected cardiac amyloidosis

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Universitary Clinic Hospital of Valencia Aim Cardiac uptake of 99mTc-DPD has proved its diagnostic efficacy in transthyretin cardiac amyloidosis(ATTR). We compared the usual visual assessment with two quantitative methods to evaluate cardiac activity and its possible relation with clinical follow-up. Methods We have studied 37 successive patients(p):32 men, 52-90 y/o (79.6 ± 9.3), submitted by suspected cardiac amyloidosis TTR by echo/cardiac MRI. After IV administration of 21.5 ± 3.4mCi of 99mTc-DPD, we obtained early (at 5min) and late (at 3h) whole body(WB) planar images and late SPECT. We assessed cardiac uptake in planar images by visual score (0-absent, 1-cardiac uptake lower than bone uptake, 2-equal, 3- higher than bone uptake), considering 2-3 score compatible with ATTR in absence of abnormal light chains on serum-urine. We obtained quantitative evaluation by heart/contralateral thoracic activity ratio (H/CL) in late images and from early and late WB images the heart retention(HR) ratio and heart/whole body(HWB) activity ratio. Clinical follow-up (12.4 ± 8.3 months) considering as cardiac events(CE): cardiac death and heart failure(HF) admissions. Results Visual score 0(11p), 1(2p), 2(4p) and 3(20p), considering group1(0-1) not suggestive of ATTR and group2(2-3) compatible with ATTR. SPECT showed biventricular uptake with septal predominance in group2. H/CL index was 2.23 ± 0.54(group2) vs 1.05 ± 0.10(group1) p &amp;lt; 0.001), according to published(≥1.5 compatible with ATTR). HR and HWB ratios were also significantly higher in group2 vs group1, respectively 6 ± 3.14vs2.17 ± 0.4(p &amp;lt; 0.001) and 6.51 ± 1.97vs2.65 ± 0.49(p &amp;lt; 0.001). There were a trend to higher values in p with visual score3 than 2, not reaching statistically significant(only 4p with visual score2). There were significant correlation between H/CL-HR(r:0.66,p &amp;lt; 0.01), H/CL-HWB(r:0.85,p &amp;lt; 0.001) and HR-HWB(r:0.85,p &amp;lt; 0.001). After follow-up we detected 6 CE(3p with HF admission, 3p cardiac death): 5p with visual score3 and one with 2, all 6p with high mean values of H/CL: 2.28 ± 0.76, HR: 6.02 ± 3.4 and HWB:5.97 ± 1.69. Conclusion We have found excellent correlation between visual score and the evaluated methods of quantitation of 99mTc-DPD cardiac uptake in our patients referred by suspected cardiac amyloidosis. These quantitative methods could be a helpful tool to correctly identify some patients with doubtful activity and could be useful in the follow-up evaluation, although it is necessary to study a greater number of patients.

Scintigraphic and echocardiographic evaluation of patients with cardiac transthyretin amyloidosis and first-degree relatives

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Pfizer Research Grant (ID#57165999) Background Misfolding of transthyretin (TTR) is the source of two distinct forms of amyloidosis (ATTR): acquired or wild-type (ATTRwt) and hereditary (ATTRm), which is transmitted in an autosomal dominant inheritance with a variable penetrance. Types of transthyretin (TTR) gene mutations display genetic and ethnic variability. Purpose The aim of this prospective study was to assess the TTR gene variants, echocardiographic parameters and regional left ventricle 99mTc-DPD uptake among patients with ATTR and first-degree relatives. Methods We present data based on evaluation of first 25 patients (13 (52%) females), including 10 (40%) index patients with ATTR (age 66.4 ± 13 years) and 15 (60%) first-degree relatives who were studied between June 2020 and February 2021. Analysis included clinical data, free light chain blood immunoglobulins and urine immunofixation, transthoracic echocardiography (TTE) with global longitudinal strain (GLS) analysis, single-photon emission computed tomography (SPECT) with 3,3-disphono-1,2-propanodicarboxylic acid (DPD), genetic testing by an amplicon-based next-generation TTR sequencing approach, and in selected cases cardiac or soft tissue biopsy. Results Overall, 6 index patients were diagnosed with ATTRm and 4 with ATTRwt presenting mixed, cardiac or neuropathic phenotype. There were detected following types of TTR variants - Phe53Leu, Ala101Val, Glu112Lys, Glu109Lys. Nine out of 10 index patients were diagnosed with amyloid cardiomyopathy (CA) with grade 2-3 tracer uptake in SPECT and symptomatic heart failure (NYHA 2.2 ± 1.1; NT-proBNP value 2224 ± 2799 pg/ml). In both ATTRm and ATTRwt there were patients presenting with either focal or diffuse tracer pattern evaluated by SPECT technique. In TTE there was marked left ventricle (LV) hypertrophy with maximum wall thickness of 22 ± 5 mm and LV mass value index value of 382 ± 111 g/m2. All patients with CA had abnormal global longitudinal strain (GLS, -14.5 ± 5%) and diastolic dysfunction (EA 1.56 ± 0.76, E/E’ 16 ± 11). None of relatives expressed tracer uptake in scintigraphy. Overall, 5 first-degree relatives were diagnosed with Phe53Leu variant, among them two patients presented with decreased GLS value. Conclusions Patients with ATTR presented in TTE with LV hypertrophy, decreased GLS value, diastolic dysfunction and grade 2-3 in scintigraphy with either focal or diffuse tracer uptake in SPECT technique. None of first-degree relatives expressed increased tracer uptake in scintigraphy. However, some of relatives who were diagnosed with pathogenic TTR variant presented with decreased GLS value.

99mTc-DPD scintigraphy in immunoglobulin light chain (AL) cardiac amyloidosis.

AimsTechnetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD scintigraphy) is recognized as highly accurate for the non-invasive diagnosis of transthyretin (ATTR) cardiac amyloidosis (CA). A proportion of patients with immunoglobulin light chain (AL) CA have also been reported to show cardiac 99mTc-DPD uptake. Herein, we assessed the frequency and degree of cardiac 99mTc-DPD uptake and its clinical significance among patients with AL CA.Methods and resultsBetween 2010 and 2017, 292 consecutive patients with AL CA underwent 99mTc-DPD scintigraphy and were included in this study: 114 (39%) had cardiac 99mTc-DPD uptake: grade 1 in 75%, grade 2 in 17%, and grade 3 in 8% of cases. Patients with cardiac 99mTc-DPD uptake had poorer cardiac systolic function and higher N-terminal pro-brain natriuretic peptide. No differences were noted in cardiac magnetic resonance parameters between patients with and without cardiac 99mTc-DPD uptake (N = 19 and 42, respectively). Patients with cardiac 99mTc-DPD uptake showed a trend to worse survival than those with no uptake (log-rank P = 0.056). Among 22 patients who underwent serial 99mTc-DPD scintigraphy, 5 (23%) showed reduction in the grade of cardiac uptake.ConclusionsIn this large cohort of patients with AL CA, 99mTc-DPD scintigraphy ∼40% of cases showed cardiac uptake, including grade 2–3 in 10% of all patients (25% of those with cardiac 99mTc-DPD uptake). Cardiac 99mTc-DPD uptake was associated with poorer cardiac function and outcomes. These data highlight the critical importance of ruling out AL amyloidosis in all patients with cardiac 99mTc-DPD uptake to ensure such patients are not assumed to have ATTR CA.

Regional cardiac uptake of 99-Tc-DPD is a novel powerful and independent prognostic marker in cardiac ATTR wild type amyloidosis

Abstract Background Skeletal scintigraphy with bone tracers is a key tool for cardiac ATTR diagnosis. However its prognostic value has not been systematically assessed. Purpose We evaluated the prognostic relevance of a quantitative method to assess regional 99mTc-DPD uptake by SPECT in the heart of ATTRwt patients. Methods All ATTRwt patients (n=229) undergoing clinical assessment and bone scintigraphy at our center (from 2012 to 2019) were enrolled. Theyreceived approximately 700 MBq of 99mTc-DPD. Planar whole body acquisition 10' after the injection followed by cardiac SPECT after 3 hours were performed. SPECT data were reconstructed into 64x64 matrices with an ordered-subset expectation maximization algorithm. For each wall region and for the apex, a circular region of interest (ROI, 20 pixels) was manually drawn and a value equating to the number of counts contained in the ROI was obtained. Partial correlation of ln-transformed ROI and biomarkers was retrieved from a multivariable regression model, while controlling for each cardiac wall region. Multivariable Cox regression was used to assess the prognostic role of lnROI while adjusting for wall region, NT-proBNP, cTnI and eGFR. Hazard ratios and 95% confidence intervals (HR, 95% CI) were computed. The Harrell's c statistic was reported for model discrimination. The interaction of biomarker and regional wall on survival was assessed; also, to account for intra-subject correlation of measures, within subject robust standard errors were computed. Results Median follow-up was 21 months (IQR 11, 40) and 39 (17%) patients died. Median age was 76 years (IQR, 72–80), NT-proBNP 2944 ng/L (IQR, 1815–5319), cTnI 0.095 ng/L (IQR, 0.062–0.144) and eGFR 62 mL/min (IQR, 51–77). ROI did not correlate with any of NT-proBNP, eGFR, age, cTnI or mLVWT (R&amp;lt;1% in all cases). All analyses were adjusted for cardiac wall. At the multivariable Cox regression (Harrell's c=0.75), there was a linear increase in the risk of death associated with lnROI (HR 2.14, P=0.014), which was independent of cardiac wall region, NTproBNP, cTnI and eGFR. Only cTnI maintained a significant prognostic value. The association of lnROI and mortality was not modified by the site of measurement test for interaction with cardiac wall p=0.818). At the predefined subgroup analysis, the risk of death was similar for all walls; we computed the optimal cut-off for 12 months survival at the apex (a region usually lately involved) to 4193 (AUC: 0.68, sensitivity 80%, specificity 68%). At the multivariable Cox regression (Harrell's c 0.76), apex ROI&amp;gt;4193 was an independent predictor of death (HR 3.60, 95% CI 1.45–8.93, p=0.006) and outperformed all the biomarkers tested. Conclusions Quantitative assessment of ROI uptake at cardiac SPECT is a powerful predictor of survival in ATTRwt patients, independent of and outperforming the other known prognostic factors. This observation warrants validation with prolonged follow-up and in independent patient series. Funding Acknowledgement Type of funding source: None

Transthyretin Cardiac Amyloidosis: Patient Characteristics in Our Region

Introduction Transthyretin cardiac amyloidosis (ATTR) is an increasingly recognized cause of heart failure (HF). The prevalence is not exactly known and a significant underdiagnosis is suspected. The objective of our study is to identify the characteristics of patients with this diagnosis in our region. Methods Prospective single-center study that included all patients (p) with cardiac ATTR diagnosis from March 2016 to January 2020. Clinical, analytical and diagnostic imaging data were collected. Results 44p were included with cardiac ATTR diagnosis confirmed by 99mTc-DPD scintigraphy (84% with intense cardiac 99mTc-DPD uptake and 16% moderate). The mean age at diagnosis was 83 years, 77% were men and 52% were in atrial fibrillation. The most frequent form of presentation was HF (61% of patients) and left ventricular hypertrophy (32%). Only 7% was a casual finding. The mean left ventricular ejection fraction was 53%, the mean thickness of the interventricular septum was 16.5 mm and the posterior wall was 13.5 mm. Only 4.5% of the cases presented signs of obstruction. Aortic stenosis was present in 25% of patients, being severe in 11% of cases. The left ventricular myocardial deformation or strain pattern was analyzed by echocardiogram in 29 patients (64%) and 97% of the patients had a compatible pattern with amyloidosis. A genetic study was performed in 68% of the individuals (30p) and 98% had the natural or wild-type form of the disease. All patients aged 80 years or older had no mutations in the TTR gene. The only patient with a familial form was diagnosed at age 76. During a median follow-up of 14 months 77% of patients had or developed HF symptoms, 57% in NYHA functional class II. 6 patients (13.5%) died during follow-up (18.5% with diagnosis due to HF and 7.1% with diagnosis due to left ventricular hypertrophy, p = 0.47). Conclusions Left ventricular myocardial strain assessment by echocardiogram is the initial diagnostic technique that provides the most value when suspecting cardiac ATTR amyloidosis. In our series the genetic study provides little value in patients older than 80 years with a compatible echocardiogram and 99mTc-DPD scintigraphy.

The Prognostic Value of Quantitative Bone SPECT/CT Before 223Ra Treatment in Metastatic Castration-Resistant Prostate Cancer.

Radiolabeled bisphosphonates such as 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) typically show intense uptake in skeletal metastases from metastatic castration-resistant prostate cancer (mCRPC). Extensive bone involvement is regarded as a risk factor for mCRPC patients treated with 223Ra-dichloride (223Ra). The aim of this study was to quantify 99mTc-DPD uptake by means of SPECT/CT before 223Ra and compare the results with the feasibility of treatment and overall survival (OS). Methods: Sixty consecutive mCRPC patients were prospectively included in this study. SPECT/CT of the central skeleton covering the skull to the mid-femoral level was performed before the first cycle of 223Ra. The bone compartment was defined by means of low-dose CT. Emission data were corrected for scatter, attenuation, and decay supplemented by resolution recovery using dedicated software. The Kaplan-Meier estimator, U test, and Cox regression analysis were used for statistics. Results: Total 99mTc-DPD uptake of the central skeleton varied between 11% and 56% of injected dose (%ID) or between 1.8 and 10.5 %ID/1,000 mL of bone volume (%ID/L). SUVmean ranged from 1.9 to 7.4, whereas the SUVmax range was 18-248. Patients unable to complete 223Ra treatment because of progression and/or cytopenia (n = 23) showed significantly higher uptake (31.9 vs. 25.4 %ID and 6.0 vs. 4.7 %ID/L; P < 0.02). OS after 223Ra (median, 15.2 mo) was reduced to 7.3 mo in cases of skeletal uptake that was 26 %ID or higher, as compared with 30.8 mo if lower than 26 %ID (P = 0.008). Similar results were obtained for %ID/L and SUVmean SUVmax did not correlate with survival. %ID/L was identified as an independent prognostic factor for OS (hazard ratio, 1.381 per unit), along with number of previous treatment lines. Conclusion: Quantitative SPECT/CT of bone scans performed at baseline is prognostic for survival in mCRPC patients treated with 223Ra.

397a Quantitative 99mTc-DPD Scintigraphy Correlation with Structural and Functional Changes on Echocardiography in Transthyretin Amyloidosis

Cardiac involvement portends poor prognosis in transthyretin amyloidosis (ATTR); increase in LV wall thickness and altered LV function are common manifestations. Our aim was to determine the correlation of LV structural (LVH and wall thickness) and functional changes (LVEF and global longitudinal strain (GLS)) on TTE with Technetium-3-3 Diphosono-1-2 propanodicarboxylic acid (99mTc-DPD) scintigraphy uptake. Hereditary and wild-type ATTR patients with TTE and 99mTc-DPD were selected. Offline measurements performed included LV average wall thickness (AWT = IVS+ PW/2), LV mass indexed (LVMI), LVEF and LV GLS. 99mTc-DPD LV uptake intensity was quantified with reference to aortic arch blood pool with custom software in Interactive Data Language (using a cut-off value of >1.1 for positive findings). Spearman rank correlation, Fisher’s Exact test and ROC curves were performed. The study cohort included 40 patients (male 75%, median age 69±22 years) with a median time difference between imaging of 7 days (IQR=100 days). 99mTc-DPD LV uptake >1.1 was evident in 75% of ATTR patients. Increased AWT (r=0.84), LVMI (r=0.80), reduction in GLS (r=0.71) (p<0.001 for all) were great predictors for increased 99mTc-DPD uptake, while reduction in LVEF (r=-0.55, p<0.001) had moderate prediction of increased uptake (Figure 1). Alterations in LV structure (increased LV AWT and LVMI) with reduced LV function in cardiac ATTR were associated with increased 99mTc-DPD uptake. Therefore, TTE could assess for LVH progression or reduction in LV function for longitudinal follow up of ATTR patients.

Quantitative bone SPECT/CT: high specificity for identification of prostate cancer bone metastases

PurposeBone scintigraphy with 99mTc-labeled diphosphonates can identify prostate cancer bone metastases with high sensitivity, but relatively low specificity, because benign conditions such as osteoarthritis can also trigger osteoblastic reactions. We aimed to investigate the diagnostic performance of 99mTc-2,3-dicarboxy propane-1,1-diphosphonate (99mTc-DPD) uptake quantification by single-photon emission computed tomography coupled with computed tomography (SPECT/CT) for distinguishing prostate cancer bone metastases from spinal and pelvic osteoarthritic lesions.MethodsWe retrospectively assessed 26 bone scans from 26 patients with known prostate cancer bone metastases and 13 control patients with benign spinal and pelvic osteoarthritic changes without known neoplastic disease. Quantitative SPECT/CT (xSPECT, Siemens Symbia Intevo, Erlangen, Germany) was performed and standardized uptake values (SUVs) were quantified with measurements of SUVmax and SUVmean (g/mL) in all bone metastases for the prostate cancer group and in spinal and pelvic osteoarthritic changes for the control group. We used receiver operating characteristics (ROC) curves to determine the optimum SUVmax cutoff value to distinguish between bone metastases and benign spinal and pelvic lesions.ResultsIn total, 264 prostate cancer bone metastases were analyzed, showing a mean SUVmax and SUVmean of 34.6 ± 24.6 and 20.8 ± 14.7 g/mL, respectively. In 24 spinal and pelvic osteoarthritic lesions, mean SUVmax and SUVmean were 14.2 ± 3.8 and 8.9 ± 2.2 g/mL, respectively. SUVmax and SUVmean were both significantly different between the bone metastases and osteoarthritic groups (p ≤ 0.0001). Using a SUVmax cutoff of 19.5 g/mL for prostate cancer bone metastases in the spine and pelvis, sensitivity, specificity, positive and negative predictive values were 87, 92, 99 and 49%, respectively.ConclusionThis study showed significant differences in quantitative 99mTc-DPD uptake on bone SPECT/CT between prostate cancer bone metastases and spinal and pelvic osteoarthritic changes, with higher SUVmax and SUVmean in metastases. Using a SUVmax cutoff of 19.5 g/mL, high specificity and positive predictive value for metastases identification in the spine and pelvis were found, thus increasing accuracy of bone scintigraphy.