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At least 109 records · Page 6

Apical sparing pattern of left ventricular myocardial {sup 99m}Tc-HMDP uptake in patients with transthyretin cardiac amyloidosis

Background: A decreased longitudinal strain in basal segments with a base-to-apex gradient has been described in patients with cardiac amyloidosis (CA). Objectives: Aim was to investigate the left ventricular (LV) regional distribution of early-phase {sup 99m}Tc-Hydroxymethylene diphosphonate ({sup 99m}Tc-HMDP) uptake in patients with transthyretin-related cardiac amyloidosis (TTR-CA). Methods: All patients underwent a whole-body planar {sup 99m}Tc-HMDP scintigraphy acquired at 10-min post-injection (early-phase) followed by a thorax SPECT/CT. The segmental uptake (expressed as % of maximal myocardial HMDP uptake) was investigated on the AHA 17-segment model and 3-segment model (basal, mid-cavity, apical). Results: Sixty-one TTR-CA patients were included of whom 29 were wild-type (wt-TTR-CA) and 32 had hereditary TTR-CA (m-TTR-CA). Early myocardial {sup 99m}Tc-HMDP uptake occurred in all TTR-CA. In all patients, segmental analysis of the LV myocardial distribution of {sup 99m}Tc-HMDP uptake showed an increased median uptake (interquartile range) in basal/mid-cavity segments compared to the lowest median uptake of apical segments (respectively, 79% [72%-86%] vs. 72% [64%-81%]; P < 10{sup −6}). This pattern was similar in wt-TTR-CA group (78% [70%-84%] vs. 70% [61%-81%]; P < 10{sup −6}), in m-TTR-CA group (80% [74%-86%] vs. 73 [66%-82%]; P < 10{sup −7}) and remained constant independently of the TTR mutation subtype with P ranging 10{sup −5} to 0.03. Conclusions: Early-phase myocardial scintigraphy identified regional distribution of {sup 99m}Tc-HMDP uptake characterized by a base-to-apex gradient, corroborating echocardiographic, and cardiac magnetic resonance findings. This apical sparing pattern was similar across TTR-CA and TTR mutation subtypes.

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Low-dose dual-isotope procedure planed for myocardial perfusion CZT-SPECT and assessed through a head-to-head comparison with a conventional single-isotope protocol

Purpose of the report: This study aimed at assessing an original low-dose dual-isotope procedure in which the abnormal stress Tc-99m Sestamibi SPECT is followed by rest Tl-201 SPECT, along with a head-to-head comparison with a single-isotope procedure. Methods and results: One hundred two patients, referred for a low-dose stress-SPECT with Sestamibi (123 ± 20 MBq) on a CZT camera and for whom a rest Sestamibi SPECT was warranted, had an additional Tl-201 rest-SPECT (52 ± 5 MBq) between stress and rest Sestamibi SPECT recordings. Tl-201 images were processed for spill-over and scatter corrections, and uptake differences with stress Sestamibi SPECT were analyzed: (1) for rest acquisitions from Tl-201 (dual-isotope procedure) and from Sestamibi (single-isotope procedure) and (2) in segments for which a diagnosis of ischemia, infarct, or normal perfusion was achieved. Mean effective dose was 8.3 mSv for dual-isotope but would decrease to 5.7 mSv for an expected rate of 37% of patients for whom rest-SPECT is not warranted. After a further background correction of Tl-201 images, the rest–stress difference in myocardial uptake was equivalent between dual- and single-procedures for identifying ischemic segments (respective areas-under-curves: 0.83 ± 0.03 and 0.81 ± 0.03). Conclusion: This original dual-isotope procedure provides acceptable radiation doses and consistent results, as compared with conventional single-isotope.

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

Background and Aim: Either 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 Results: We 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. Conclusions: Tc-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.

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Comparison of CZT SPECT and conventional SPECT for assessment of contractile function, mechanical synchrony and myocardial scar in patients with heart failure

Aim: The aim of this study was to compare CZT-SPECT (CZT SPECT) to conventional SPECT (C-SPECT) in the assessment of left ventricular myocardial scar, contractile function, and mechanical synchrony in patients with heart failure (HF). Methods: Fifty-nine patients with HF who were referred for myocardial perfusion/metabolism imaging were enrolled. All patients underwent resting {sup 99m}Tc-MIBI gated myocardial perfusion imaging using a CZT SPECT camera and a C-SPECT camera, respectively, and {sup 18}F-FDG PET myocardial metabolism imaging within three days. Summed rest score (SRS) and total perfusion defect (TPD) (as indices of perfusion abnormality), left ventricular (LV), end diastolic volume (EDV), end systolic volume (ESV), and ejection fraction (EF) (as indices of LV systolic function), and histogram band width (BW) and standard deviation (SD) (as indices of mechanical synchrony) were analyzed by automated software while the perfusion/metabolism patterns were analyzed visually. Results: There was a good correlation between CZT SPECT and C-SPECT for SRS and TPD. CZT SPECT tended to underestimate SRS and TPD compared to C-SPECT. CZT-SPECT and C-SPECT showed excellent agreement in assessing the perfusion/metabolism pattern though a small proportion of normal segments (6.6%) identified by CZT/PET exhibited mismatch pattern on C-SPECT/PET. CZT SPECT also showed excellent correlation with C-SPECT in measuring EDV, ESV, and EF. Finally, BW and SD measured by CZT SPECT correlated well with C-SPECT but CZT SPECT tended to overestimate BW and SD compared to C-SPECT. Conclusion: CZT SPECT provided comparable data to C-SPECT for measuring LV scar, function and synchrony at a considerable reduction in imaging time. CZT SPECT holds a promise for comprehensive evaluation of myocardial performance in patients with HF.

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Quantification of intramyocardial blood volume with {sup 99m}Tc-RBC SPECT-CT imaging: A preclinical study

Background: Currently, there is no established non-invasive imaging approach to directly evaluate myocardial microcirculatory function in order to diagnose microvascular disease independent of co-existing epicardial disease. In this work, we developed a methodological framework for quantification of intramyocardial blood volume (IMBV) as a novel index of microcirculatory function with SPECT/CT imaging of {sup 99m}Tc-labeled red blood cells (RBCs). Methods: Dual-gated myocardial SPECT/CT equilibrium imaging of {sup 99m}Tc-RBCs was performed on twelve canines under resting conditions. Five correction schemes were studied: cardiac gating with no other corrections (CG), CG with attenuation correction (CG + AC), CG + AC with scatter correction (CG + AC + SC), dual cardiorespiratory gating with AC + SC (DG + AC + SC), and DG + AC + SC with partial volume correction (DG + AC + SC + PVC). Quantification of IMBV using each approach was evaluated in comparison to those obtained from all corrections. The in vivo SPECT estimates of IMBV values were validated against those obtained from ex vivo microCT imaging of the casted hearts. Results: The estimated IMBV with all corrections was 0.15 ± 0.03 for the end-diastolic phase and 0.11 ± 0.03 for the end-systolic phase. The cycle-dependent change in IMBV (ΔIMBV) with all corrections was 23.9 ± 8.6%. Schemes that applied no correction or partial correction resulted in significant over-estimation of IMBV and significant under-underestimation of ΔIMBV. Estimates of IMBV and ΔIMBV using all corrections were consistent with values reported in the literature using invasive techniques. In vivo SPECT estimates of IMBV strongly correlated (R{sup 2} ≥ 0.70) with ex vivo measures for the various correction schemes, while the fully corrected scheme yielded the smallest bias. Conclusions: Non-invasive quantification of IMBV is feasible using {sup 99m}Tc-RBCs SPECT/CT imaging, however, requires full compensation of physical degradation factors.

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Effects of cardiac resynchronization therapy on right ventricular function during rest and exercise, as assessed by radionuclide angiography, and on NT-proBNP levels

Aim: We carried out this study to investigate mid-term effects of cardiac resynchronization therapy (CRT) on right ventricular (RV) function and neurohormonal response, expressed by N-terminal pro-brain natriuretic peptide (NT-proBNP), in heart failure patients stratified by baseline RV ejection fraction (RVEF). Methods and Results: Thirty-six patients with nonischemic dilated cardiomyopathy underwent technetium-99m radionuclide angiography with bicycle exercise immediately after CRT implantation (during spontaneous rhythm and after CRT activation) and 3 months later. Plasma NT proBNP was assessed before implantation and after 3 months. At baseline, RVEF was impaired (≤35%) in 14 patients, preserved (>35%) in 22. At 3 months, RVEF improved during rest and exercise (P = .02) in patients with impaired RV function, while remaining unchanged in patients with preserved RV function. Rest and exercise RV dyssynchrony decreased in both groups at follow-up (P < .05). A similar mid-term improvement in left ventricular (LV) function and NT-proBNP was observed in patients with impaired and preserved RVEF. In the former, the decrease in NT-proBNP correlated with the improvements both in LV and RV dyssynchrony and functions. Conclusion: CRT may improve RV performance, during rest and exercise, and neurohormonal response in heart failure patients with nonischemic dilated cardiomyopathy and baseline RV dysfunction. RV dysfunction should not be considered per se a primary criterion for excluding candidacy to CRT.

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A combined static-dynamic single-dose imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT

Background: SPECT myocardial perfusion imaging (MPI) is a clinical mainstay that is typically performed with static imaging protocols and visually or semi-quantitatively assessed for perfusion defects based upon the relative intensity of myocardial regions. Dynamic cardiac SPECT presents a new imaging technique based on time-varying information of radiotracer distribution, which permits the evaluation of regional myocardial blood flow (MBF) and coronary flow reserve (CFR). In this work, a preliminary feasibility study was conducted in a small patient sample designed to implement a unique combined static-dynamic single-dose one-day visit imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT for improving the diagnosis of coronary artery disease (CAD). Methods: Fifteen patients (11 males, four females, mean age 71 ± 9 years) were enrolled for a combined dynamic and static SPECT (Infinia Hawkeye 4, GE Healthcare) imaging protocol with a single dose of {sup 99m}Tc-tetrofosmin administered at rest and a single dose administered at stress in a one-day visit. Out of 15 patients, eleven had selective coronary angiography (SCA), 8 within 6 months and the rest within 24 months of SPECT imaging, without intervening symptoms or interventions. The extent and severity of perfusion defects in each myocardial region was graded visually. Dynamically acquired data were also used to estimate the MBF and CFR. Both visually graded images and estimated CFR were tested against SCA as a reference to evaluate the validity of the methods. Results: Overall, conventional static SPECT was normal in ten patients and abnormal in five patients, dynamic SPECT was normal in 12 patients and abnormal in three patients, and CFR from dynamic SPECT was normal in nine patients and abnormal in six patients. Among those 11 patients with SCA, conventional SPECT was normal in 5, 3 with documented CAD on SCA with an overall accuracy of 64%, sensitivity of 40% and specificity of 83%. Dynamic SPECT image analysis also produced a similar accuracy, sensitivity, and specificity. CFR was normal in 6, each with CAD on SCA with an overall accuracy of 91%, sensitivity of 80%, and specificity of 100%. The mean CFR was significantly lower for SCA detected abnormal than for normal patients (3.86±1.06 vs 1.94±0. 0.67, P < 0.001). Conclusions: The visually assessed image findings in static and dynamic SPECT are subjective, and may not reflect direct physiologic measures of coronary lesion based on SCA. The CFR measured with dynamic SPECT is fully objective, with better sensitivity and specificity, available only with the data generated from the dynamic SPECT method.

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Interactions between myocardial sympathetic denervation and left ventricular mechanical dyssynchrony: A CZT analysis

Background: A correlation between left ventricular (LV) dyssynchrony (LVD) and impaired myocardial sympathetic tone has been hypothesized. We sought to assess the interactions between regional LV sympathetic innervation, perfusion, and mechanical dyssynchrony. Methods: Eighty-three patients underwent evaluation of LV perfusion and sympathetic innervation on {sup 99m}Tc-tetrofosmin/{sup 123}I-metaiodobenzylguanidine ({sup 123}I-MIBG) imaging. The summed rest score and summed {sup 123}I-MIBG score (SS-MIBG) were computed. The extent of “innervation/perfusion” mismatch was defined as the number of denervated LV segments with relatively preserved perfusion. LVD was evaluated on phase analysis and the wall with latest mechanical activation identified. Results: LVD was revealed in 36 (43%) patients. Patients with LVD had more abnormal values of SRS (21 ± 9 vs 10 ± 8, P < 0.001) and SS-MIBG (29 ± 9 vs 17 ± 11, P < 0.001) than those without LVD. The presence of LVD also clustered with a higher burden of “innervation/perfusion” mismatch (P = 0.019). On per-wall analysis, LV walls with delayed mechanical activation showed a higher burden of “innervation/perfusion” mismatch (2.3 ± 1.4 segments) than normally contracting walls (1.3 ± 1.2 segments; P < 0.001). On multivariate analysis, the extent of “innervation/perfusion” mismatch was the only predictor of delayed mechanical activation (P = 0.029). Conclusions: Patients with LVD show an elevated burden of “innervation/perfusion” mismatch that is concentrated at the level of the most dyssynchronous walls.

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Improved diagnosis of the number of stenosed coronary artery vessels by segmentation with scatter and photo-peak window data for attenuation correction in myocardial perfusion SPECT

Background: Attenuation correction using segmentation of scatter and photo-peak window data (SSPAC) enables an evaluation of the attenuation map in a patient-specific manner without additional radiation exposure. We compared the accuracy of SSPAC and non-corrected myocardial perfusion scintigraphy methods for diagnosing the number of stenosed coronary artery vessels. Methods and Results: We retrospectively reviewed the data from 183 consecutive patients who underwent {sup 99m}Tc-tetrofosmin stress/rest SPECT examination and a coronary angiography within 3 months. The MPS images were reconstructed with and without SSPAC attenuation correction. We examined the accuracy of the quantitative interpretation using summed differential score in the detection of coronary artery disease (CAD). The attenuation maps were successfully determined in 179 of 183 patients (98%). In terms of the vessel-based diagnostic ability, sensitivity, specificity, positive predictive and negative predictive values of the SSPAC and non-correction methods for diagnosing CAD in individual coronary territories were 77%*, 89%, 74%*, and 90%* vs 51%, 87%, 62%, and 82%, respectively (*P < .05). In 35 patients with multi-vessel CAD, those values were 78%*, 81%, 93%, and 55%* vs 49%, 81%, 89%, and 34%, respectively (*P < .05; AUC: 0.82 vs 0.62, P < .05). Conclusion: SSPAC-corrected SPECT myocardial perfusion images exhibit improved accuracy in the detection of the number of stenosed coronary artery vessels, even in patients with multi-vessel CAD.

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Prediction of long-term (> 10 year) cardiovascular outcomes in heart transplant recipients: Value of stress technetium-99m tetrofosmin myocardial perfusion imaging

Background: Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) is useful in the evaluation of cardiac allograft vasculopathy (CAV) in heart transplant (HTx) recipients. The current study evaluated the long-term prognostic value of stress SPECT MPI for predicting all-cause mortality and cardiac events in HTx recipients. Methods: The study population consisted of 166 HTx recipients (mean age 54 ± 10 years, 84% male) who underwent exercise or dobutamine stress {sup 99m}Tc-tetrofosmin SPECT MPI for the assessment of CAV. An abnormal SPECT MPI was defined as the presence of a fixed or a reversible perfusion defect. Endpoints were all-cause mortality, cardiac mortality, and non-fatal myocardial infarction (MI). Results: MPI abnormalities were detected in 55 patients (33%), including fixed defects in 28 patients (17%), partially reversible in 17 patients (10%), and completely reversible defects in 10 patients (6%). During a median follow-up of 12.8 years (range 0-15, mean follow-up 9.5 years), 109 (66%) patients died (all-cause mortality), of which 67 (40%) were due to cardiac causes. A total of 5 (3%) patients experienced a non-fatal MI. HTx recipients with a normal stress {sup 99m}Tc-tetrofosmin SPECT MPI had a significantly better prognosis as compared with those with an abnormal study, up to 5 years after the initial test. The presence of a reversible perfusion defect was a significant predictor of all-cause mortality, cardiac mortality, and major cardiac events, during the entire follow-up period. Conclusions: Stress {sup 99m}Tc-tetrofosmin SPECT MPI provides valuable prognostic information for the prediction of long-term outcome in HTx recipients. Patients with a normal stress {sup 99m}Tc-tetrofosmin SPECT MPI have a significantly better prognosis as compared with those with an abnormal study, up to 5 years after initial testing.

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Additional value of systolic wall thickening in myocardial stunning evaluated by stress-rest gated perfusion SPECT

Aim and patients: The aim of the present study is to evaluate the additional value of systolic wall thickening to myocardial perfusion in diagnosing myocardial stunning in patients with angiography proven coronary artery disease. We selected 91 ischemic patients (82 males; mean age 59.7 ± 10.3) with CAD documented by angiography. Ischemia was defined as a summed difference score ≥5. All patients underwent a 2-day gated perfusion SPECT protocol. The patients received a dose of 740 MBq of {sup 99m}Tc-tetrofosmin after stress and at rest. Treadmill maximal exercise tests were performed on all patients. Results: The post-stress LVEF was significantly lower than rest LVEF (48.1% ± 10.3% vs 50.3% ± 10.7%; P = .0001). The wall thickening summed difference score was 4.44 ± 4.13 (P = .0001). At a multivariate regression analysis, only WT-SDS as independent variable was significantly correlated with myocardial ischemia (SDS). We also divided patients according to SDS in those with mild (SDS < 8) and severe (SDS ≥ 8) ischemia. WT-SDS, but not ∆LVEF, was significantly different between groups. Conclusions: WT-SDS, more than the depression in the global function (∆LVEF) of the left ventricle, correlates with the degree of ischemia and better identifies, when present, the stunning phenomenon.

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Non-cardiac uptake of technetium-99m pyrophosphate in transthyretin cardiac amyloidosis

Background: Technetium-based bone scintigraphy is rapidly becoming the most common non-invasive imaging tool in the diagnosis of Transthyretin cardiac amyloidosis (ATTR). Skeletal muscle uptake has been described with technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (TcDPD), and may account for masking of bony uptake. We sought to investigate skeletal muscle uptake of technetium-99m-pyrophosphate (TcPYP) in patients with ATTR. Methods and Results: This was a retrospective analysis of 57 patients diagnosed with ATTR who underwent TcPYP scintigraphy. Cardiac uptake was assessed on whole-body planar imaging using a semiquantitative scale (grades 0 to 3) and on single-photon emission computed tomography (SPECT) with CT attenuation correction using total myocardial counts per voxel after a 3-hour incubation. Skeletal muscle (psoas and biceps), vertebral body, LV myocardium, and blood pool mean counts were calculated. In the cohort (age 78 ± 9 years, 77% male, and 30% hereditary ATTR), there was no visualized tracer uptake in skeletal muscle or soft tissue on qualitative SPECT assessment. Total and blood pool-corrected uptake in the muscle groups were significantly less than myocardium and bone (P < 0.001). Blood pool-corrected muscle uptake was not associated with semiquantitative grade 3 vs 2 uptake (psoas P = 0.66, biceps P = 0.13) or presence of hereditary ATTR (psoas P = 0.43, biceps P = 0.69). As bony uptake decreased, there was no corresponding increase in skeletal muscle uptake. Conclusions: In patients with ATTR cardiac amyloidosis, skeletal muscle uptake of TcPYP is minimal when assessed by qualitative and quantitative metrics, and is not significantly different in patients with grade 2 vs 3 semiquantitative uptake. The properties of this tracer may be different than TcDPD with respect to non-cardiac uptake.

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Gated SPECT myocardial perfusion imaging with cadmium-zinc-telluride detectors allows real-time assessment of dobutamine-stress-induced wall motion abnormalities

Background: Left ventricular (LV) ejection fraction (EF) during high dobutamine stress (HD) by real-time gated-SPECT myocardial perfusion imaging (MPI) on a cadmium-zinc-telluride (CZT) gamma camera was validated versus cardiac magnetic resonance imaging (CMR). Methods and results: After injecting 99mTc-tetrofosmin (320 MBq) in 50 patients (mean age 64 +/− 11 years), EF at rest and post-stress as well as relevant changes in EF at HD (ΔEF ≥ 5%) were assessed. CZT and CMR rest EF values yielded an excellent correlation and agreement (r = 0.96; P < 0.001; Bland–Altman limits of agreement (BA): + 0 to 14.8%). HD EF acquisition was feasible using CZT and correlated better to HD CMR EF than did post-stress CZT EF (r = 0.85 vs 0.76, respectively, all P < 0.001). Agreement in ΔEF detection between HD CMR and immediate post-stress CZT (reflecting standard acquisition using conventional SPECT camera unable to scan during stress) was 45%, while this increased to 85% with real-time HD CZT scan. Conclusion: Real-time ultrafast dobutamine gated-SPECT MPI with a CZT device is feasible and provides accurate measurements of HD LV performance.

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Diagnostic value of stress thallium-201/rest technetium-99m-sestamibi sequential dual isotope high-speed myocardial perfusion imaging for the detection of haemodynamically relevant coronary artery stenosis

Background: The aim of this study was to determine the diagnostic accuracy of stress thallium-201/rest technetium-99m-sestamibi sequential dual-isotope high-speed myocardial perfusion imaging (DI-HS-MPI) against invasively determined fractional flow reserve (FFR). Methods: Fifty-four consecutive patients prospectively underwent DI-HS-MPI before invasive coronary angiography. Perfusion was scored visually by summed stress score on a patient and coronary territory basis. Significant coronary artery disease (CAD) was defined by the presence of ≥ 90% stenosis/occlusion or fractional flow reserve ≤ 0.80 for coronary stenosis ≥ 50%. Results: FFR was measured in 69 of 162 coronary vessels, with 1.28 ± 0.56 vessels assessed/patient. Sensitivity, specificity, and diagnostic accuracy of MPI for the detection of significant CAD were 92.8%, 69.2%, and 81.4%, on a patient basis, and 83.7%, 90.4%, and 88.8% by coronary territory. Conclusions: DI-HS-MPI accurately detects functionally significant CAD as defined by using FFR.

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Imaging doxorubicin and polymer-drug conjugates of doxorubicin-induced cardiotoxicity with bispecific anti-myosin-anti-DTPA antibody and Tc-99m-labeled polymers

Background: Radiolabeled anti-myosin imaging is well-established for imaging doxorubicin-induced cardiotoxicity. However, to enable imaging of drug-induced cardiotoxicity in small experimental animals, pretargeting with bispecific anti-myosin-anti-DTPA-Fab-Fab’ and targeting with high-specific radioactivity Tc-99m-DTPA-succinylated-polylysine (DSPL) was developed. Methods: Mice were injected biweekly with 10 mg/kg Dox or its equivalent as D-Dox-PGA. Tc-99m-DSPL myocardial activity after pretargeting with bsAb-Fab-Fab’ was determined after gamma imaging performed at day 7 for Dox-treated mice and day 39 for all others. Results: Mice treated with 10 mg/kg Dox lost 10% total body weight in 1 week and 20% after a second dose. Pretargeted mice treated with 30 mg/kg cumulative D-Dox-PGA dose showed no loss of body weight for the duration of the study. Cardiotoxicity was confirmed by gamma imaging and scintillation counting (1.9 ± 0.25 [mean% ID/g ± SD]) after 1 dose of Dox. Mice injected with 3 × 10 mg/kg Dox equivalent as D-Dox-PGA (0.4 ± 0.04, P < .01) and untreated 2 control groups (0.20 ± 0.05 and 0.19 ± 0.04, P < .01) showed significantly lower myocardial anti-myosin radioactivity relative to the 10 mg/kg Dox group. Conclusion: Pretargeting with bsAb-Fab-Fab’ and targeting with Tc-99m labeled high-specific activity polymers enabled early visualization of doxorubicin induce cardiotoxicity in mice. Tolerated dose of D-Dox-PGA was greater than to 30 mg/kg Dox-equivalent dose with minimal cardiotoxicity.

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