The value of Tc-99m MIBI SPECT during isosorbide dinitrate infusion in assessment of viable myocardium in patients with myocardial infarction

Tc-99m MIBI myocardial SPECT has shown promise for evaluation of coronary artery disease. But its role in predicting myocardial viability is still under investigation. The purpose of this study was to evaluate the value of Tc-99m MIBI myocardial SPECT during isosorbide dinitrate (ISDN) infusion in the assessment of myocardial viability. Thirty-seven patients with previous myocardial infarction (the infarct age ranged from ≤ 30 days to 900 days) were studied, of them 13 patients had Tc-99m MIBI studies before and after coronary artery bypass grafting (CABG). The results showed that out of 134 segments with hypoperfusion at resting SPECT, 56 segments (41.8%) had an increase in Tc-99m MIBI uptake during ISDN infusion. Among them, 17 segments (30.4%) were normalized, 6 segments (10.7%) were significantly improved and 33 segments (58.9%) were improved. The degree of improvement in perfusion was related to the age of the myocardial infarction. In 13 patients with CABG, of 31 segments with improvement in perfusion post CABG, 25 segments (80.6%) showed perfusion improvement during ISDN infusion, and of 28 segments with improved wall motion post CABG, 23 segments (82.1 %) showed improvement in perfusion during ISDN infusion. Tc-99m MIBI SPECT during ISDN infusion may therefore be a useful approach for assessing myocardial viability.     

Technetium 99m-labeled sestamibi imaging reliably identifies retained contractile reserve in dyssynergic myocardial segments

Background

Recently there has been considerable controversy regarding the use of ^99mTc-labeled sestamibi as an agent for the detection of viable myocardium. In this study we have used dobutamine-induced left ventricular wall thickening by echocardiography in regions with evidence of resting dyssynergy of the left ventricle as an indicator of retained contractile reserve and compared this with 99m Tc-labeled sestamibi uptake in the same regions.

Methods and Results

Twenty-seven patients with documented coronary artery disease and severe regional wall motion abnormalities underwent low-dose (5 to 15 μg/kg/min) dobutamine echocardiography and maximal (15 to 40 μg/kg/min) stress dobutamine ^99mTc-labeled sestamibi single-photon emission computed tomographic imaging. Separate-day rest ^99mTc-labeled sestamibi scanning was also performed. ^99mTc-labeled sestamibi uptake was assessed semiquantitatively from grades from 1 to 4, from normal to absent perfusion. Regions with grade 3 or less uptake were considered viable by ^99mTc-labeled sestamibi. Of the 34 regions with severe wall motion abnormalities by echocardiography, 32 showed improved wall thickening with low-dose dobutamine. Rest ^99mTc-labeled sestamibi detected retained myocardial viability in 29 of these regions (91%) that were deemed to have contractile reserve by echocardiography (concordance: 91% [K=0.53; p<0.001]). Furthermore, stress-rest ^99mTc-labeled sestamibi revealed completely reversible defects in five regions (16%), partially reversible defects in 24 regions (75%), and grade 4 uptake and fixed (nonviable) defects in three (9%) of these 32 regions with retained contractile reserve.

Conclusion

Uptake of ^99mTc-labeled sestamibi at rest accurately identifies regions of segmental dyssynergy in which recovery of function may be provoked by inotropic stimulation. Addition of stress dobutamine ^99mTc-labeled sestamibi provides further proof of retained myocardial viability in these dysfunctional segments.     

Technetium 99m-labeled tetrofosmin myocardial tomography in patients with coronary artery disease: Comparison between adenosine and dynamic exercise stress testing

Background

Pharmacologic coronary vasodilation with adenosine, combined with myocardial scintigraphy, is a useful test for the diagnosis of coronary artery disease (CAD) in patients unable to exercise. It has been demonstrated recently that exercise ^99mTc-labeled tetrofosmin cardiac imaging can be used for the detection of CAD. However, no data are available comparing ^99mTc-labeled tetrofosmin adenosine and exercise tests in the same patients.

Methods and Results

The results of adenosine and exercise ^99mTc-labeled tetrofosmin myocardial tomography were compared in 41 patients (37 men and four women; mean age 53±8 years) with suspected or known CAD who underwent coronary angiography. All patients were submitted, on separate days, to three injections of ^99mTc-labeled tetrofosmin (740 MBq intravenously): one at rest, one during bicycle exercise, and one during adenosine infusion (140 μg/kg/min for 6 minutes with injection of ^99mTc-labeled tetrofosmin at 4 minutes). A total of 902 myocardial segments were analyzed quantitatively. One patient had normal coronary vessels, 19 patients had single-vessel CAD, 12 patients had two-vessel CAD, and nine patients had three-vessel CAD (>50% coronary stenosis) on coronary angiography. Adenosine induced a significant increase in heart rate (88±16 beats/min at peak vs 72±11 beats/min at rest; p<0.01). Systolic and diastolic blood pressure was not significantly different after adenosine infusion compared with rest. Double product was 22931 ± 7039 at peak exercise and 11229±3413 after adenosine (p<0.01). Agreement on the presence of abnormal single-photon emission computed tomography by adenosine and exercise was 100% by quantitative analysis. In all segments a significant relationship between exercise and adenosine ^99mTc-99m-labeled tetrofosmin uptake was observed (r=0.90; p<0.001). Segmental agreement for regional ^99mTc-labeled tetrofosmin uptake score between exercise and adenosine was observed in 737 (82%) of the 902 segments (kappa value of 0.66). Concordance between the two studies for identification of perfusion status was observed in 809 (90%) of the segments (kappa value of 0.80). Sensitivity and specificity for detection of stenosed vessels were not different for dynamic exercise stress testing and adenosine ^99mTc-labeled tetrofosmin cardiac tomography.

Conclusions

Despite different hemodynamic effects, adenosine and dynamic exercise ^99mTc-labeled tetrofosmin single-photon emission computed tomographic imaging provides similar information in the diagnosis and localization of CAD.     

Left ventricular dysfunction in coronary artery disease: Comparison between rest-redistribution thallium 201 and resting technetium 99m methoxyisobutyl isonitrile cardiac imaging

Background

We compared rest-redistribution thallium 201 and resting technetium 99m methoxyisobutyl isonitrile (MIBI) cardiac imaging in 29 men with angiographically proven coronary artery disease and regional ventricular dysfunction. Left ventricular ejection fraction at radionuclide angiography was 35%±9%.

Methods and Results

Regional left ventricular wall motion was assessed on gated^99mTc MIBI images according to a 3-point scale (0=normal, 1=hypokinetic, 2=akinetic or dyskinetic).²⁰¹Tl and^99mTc MIBI uptake values were analyzed quantitatively. A total of 435 myocardial segments were classified on the basis of wall motion analysis into three groups: group 1 (normal wall motion;n=201), group 2 (hypokinetic;n=132), and group 3 (akinetic or dyskinetic;n=102).²⁰¹Tl and^99mTc MIBI uptake values were significantly higher in groups 1 and 2 compared with group 3 (p<0.05) and in group 1 compared with group 2 (p<0.05). When²⁰¹Tl and^99mTc MIBI uptake values were directly compared, no significant differences in groups 1 and 2 were observed. In group 3,^99mTc MIBI uptake (67%±14%) was significantly lower (p<0.001) than initial (72%±11%) and delayed²⁰¹Tl uptake (73%±12%).

Conclusion

Thus rest-redistribution²⁰¹Tl and resting^99mTc MIBI cardiac imaging reflect the severity of left ventricular dysfunction in coronary artery disease. However, in segments with severely impaired regional ventricular function,²⁰¹Tl uptake is significantly higher than^99mTc MIBI uptake.     

Adenosine coronary vasodilation quantitative technetium 99m methoxy isobutyl isonitrile myocardial tomography in the identification and localization of coronary artery disease

Background

Exercise and dipyridamole ^99mTc-labeled methoxy isobutyl isonitrile (MIBI) myocardial scintigraphy have been widely used for the diagnosis of coronary artery disease (CAD). However, only limited data on adenosine ^99mTc-labeled MIBI cardiac imaging are currently available. This study was designed to assess the accuracy of quantitative adenosinerest ^99mTc-labeled MIBI tomography in the diagnosis and localization of CAD.

Methods and Results

Fifty-seven consecutive patients with suspected CAD who underwent coronary angiography and 22 normal volunteers were studied. All patients underwent ^99mTc-labeled MIBI tomography after administration of adenosine (140 μg/kg intravenously for 6 minutes) and at rest. A total of 171 vascular coronary territories were analyzed quantitatively. All patients with CAD (≥50% luminal stenosis) (n=55) had abnormal ^99mTc-labeled MIBI tomograms. The normalcy rate was 86% by quantitative analysis. Overall sensitivity, specificity, and diagnostic accuracy for detection of individual stenosed vessels were 84%, 87%, and 85%, respectively. In patients with one-vessel CAD (n=24), sensitivity and diagnostic accuracy in the detection of individual stenosed vessels were significantly (p<0.05) higher compared with patients with multivessel CAD (n=31). Moreover, 75% of patients with one-vessel disease showed a scintigraphic pattern characterized by the presence of perfusion defects in only one coronary artery territory, and 74% of patients with multivessel disease showed a scintigraphic pattern characterized by the presence of perfusion defects in two or more coronary artery territories. Sensitivity, specificity, and diagnostic accuracy for detecting individual diseased vessels were similar in patients without previous myocardial infarction (n=18) compared with those with previous myocardial infarction (n=39). In myocardial territories related to noninfarcted areas (n=124), sensitivity and specificity in the detection of stenosed vessels were 75% and 88%. In infarcted areas (n=47), sensitivity and specificity in the detection of stenosed vessels were 98% and 80% (differences not significant vs noninfarcted areas).

Conclusions

Adenosine-controlled coronary vasodilation combined with quantitative ^99mTc-labeled MIBI tomography is accurate for identifying patients with CAD and localizing individual stenosed coronary arteries.     

Reversible ischemia in severe stress technetium 99m-labeled sestamibi perfusion defects assessed from gated single-photon emission computed tomographic polar map fourier analysis

Background  

Detection of reversible ischemia and regional viability by inference from the presence of preserved resting myocardial thickening on dynamic electrocardiographic-gated tomographic (GSPECT) images obtained after stress injection could potentially obviate the need for a separate resting injection. This would decrease the cost, effort, duration, and radiation exposure of diagnostic myocardial perfusion imaging. The aim of this study was to determine whether functional images derived from GSPECT stress myocardial perfusion images, which represent indices of regional wall thickening, could predict the pattern of reversibility of perfusion defects in myocardial segments with severe perfusion defects on stress ^99mTc-labeled sestamibi (^99mTc-sestamibi) images.     

Impaired Coronary Flow Reserve Is the Most Important Marker of Viable Myocardium in the Myocardial Segment-Based Analysis of Dual-Isotope Gated Myocardial Perfusion Single-Photon Emission Computed Tomography

Objective

The aim of this study was to investigate the most robust predictor of myocardial viability among stress/rest reversibility (coronary flow reserve [CFR] impairment), ²⁰¹Tl perfusion status at rest, ²⁰¹Tl 24 hours redistribution and systolic wall thickening of ^99mTc-methoxyisobutylisonitrile using a dual isotope gated myocardial perfusion single-photon emission computed tomography (SPECT) in patients with coronary artery disease (CAD) who were re-vascularized with a coronary artery bypass graft (CABG) surgery.

Materials and Methods

A total of 39 patients with CAD was enrolled (34 men and 5 women), aged between 36 and 72 years (mean 58 ± 8 standard in years) who underwent both pre- and 3 months post-CABG myocardial SPECT. We analyzed 17 myocardial segments per patient. Perfusion status and wall motion were semi-quantitatively evaluated using a 4-point grading system. Viable myocardium was defined as dysfunctional myocardium which showed wall motion improvement after CABG.

Results

The left ventricular ejection fraction (LVEF) significantly increased from 37.8 ± 9.0% to 45.5 ± 12.3% (p < 0.001) in 22 patients who had a pre-CABG LVEF lower than 50%. Among 590 myocardial segments in the re-vascularized area, 115 showed abnormal wall motion before CABG and 73.9% (85 of 115) had wall motion improvement after CABG. In the univariate analysis (n = 115 segments), stress/rest reversibility (p < 0.001) and ²⁰¹Tl rest perfusion status (p = 0.024) were significant predictors of wall motion improvement. However, in multiple logistic regression analysis, stress/rest reversibility alone was a significant predictor for post-CABG wall motion improvement (p < 0.001).

Conclusion

Stress/rest reversibility (impaired CFR) during dual-isotope gated myocardial perfusion SPECT was the single most important predictor of wall motion improvement after CABG.     

Experimental verification of technetium 99m-labeled teboroxime kinetic parameters the the myocardium with dynamic single-photon emission computed tomography: Reproducibility,correlation to flow,and susceptibility to extravascular contamination

Background

This research was undertaken to investigate the ability of dynamic singlephoton emission computed tomographic (SPECT) imaging to quantify myocardial perfusion in vivo with ^99mTc-labeled teboroxime. The objectives of this experiment were (1) to determine the reproducibility of the model parameters f_v, K₁, and k₂ (volume fraction of blood in the tissue and wash-in and wash-out of ^99mTc-labeled teboroxime correlate, with an independent measure of myocardial blood perfusion, and (3) to determine the amount of extravascular activity in the arterial blood time-activity curve generated from the dynamic SPECT images

Methods and Results

Twenty-nine studies were performed on 10 dogs. The dogs were divided into three groups: reproducibility, occlusion, and vasodilation. In the reproducibility protocol, the physiology was kept as constant as possible. In the occlusion and vasodilation protocols, myocardial perfusion was either decreased by occluding the left anterior descending coronary artery or increased by continuous adenosine infusion, respectively. In all studies an independent measure of myocardial perfusion was obtained with either radiolabeled microspheres or a flow probe, and the activity of ^99mTc-labeled teboroxime in the arterial blood was monitored continuously. The root-mean-square errors calculated with data from the reproducibility group were 19.9%±8.5%, 14.0%±5.7%, and 14.5%±5.0% for f_v, K₁, and k₂, respectively. The occlusion group data showed that K₁ demonstrated a higher correlation (r=0.887) with microsphere myocardial perfusion than did k₂ (r=0.689). The results from the vasodilation group showed that K₁ demonstrated a stronger relationship to myocardial blood flow (MBF) measured with a flow probe (K₁=0.237+0.629 MBF [r=0.935] and k₂=0.177+0.263 MBF [r=0.904]). Finally, the amount of extravascular activity in the blood time-activity curve generated from the dynamic SPECT images was determined to be 45.5%±16.4%.

Conclusions

The wash-in parameter K₁ correlates with myocardial perfusion in dogs; therefore dynamic SPECT imaging of ^99mTc-labeled teboroxime has the potential for measuring regional myocardial perfusion in patients.     

Kinetic characterization of a novel cationic <Superscript>99m</Superscript>Tc(I)-tricarbonyl complex, <Superscript>99m</Superscript>Tc-15C5-PNP,for myocardial perfusion imaging

Background  

Intense liver uptake of ^99mTc-sestamibi (MIBI) often interferes with visualization of myocardial perfusion in the inferior wall of the left ventricle. To develop improved myocardial perfusion agents, crown ether-containing dithiocarbamates and bisphosphines have been introduced in recent years. This study was designed to investigate the myocardial imaging properties and in vivo kinetics of a cationic ^99mTc(I)-tricarbonyl complex, ^99mTc-15C5-PNP, in comparison with MIBI.     

Tolerance,hemodynamic changes,and safety of dobutamine stress perfusion imaging

Background

Dobutamine myocardial perfusion perfusion imaging is being used increasingly for assessment of coronary artery disease. Heretofore, there have been no large series documenting its tolerance and safety. The aims of this study were to assess the tolerance, hemodynamic changes, and safety of dobutamine stress in conjunction with myocardial perfusion imaging.

Methods and Results

The tolerance, hemodynamic changes, and safety of dobutamine myocardial perfusion imaging were investigated in a consecutive series of 1012 patients. Dobutamine was infused at incremental doses of 10, 20, 30, and 40 μg/kg/min at 3-minute intervals. Perfusion tomography was performed according to standard protocols with either ²⁰¹Tl or ^99mTc-labeled sestamibi. Seven hundred twenty-nine patients (72%) reached a maximal dobutamine dose of 40 μg/kg/min. Dobutamine significantly increased heart rate (76±14 beats/min to 127±20 beats/min; p<0.001) and systolic blood pressure (141±20 mm Hg to 168±36 mm Hg; p<0.001) from baseline to peak infusion rate. The most common side effects were chest pain (31%), headache (14%), dyspnea (12%), palpitations (10%), and flushing (10%). There was no death, myocardial infarction, pulmonary edema, ventricular fibrillation, sustained ventricular tachycardia, or cerebral vascular accident. Nonsustained ventricular tachycardia occurred in 43 patients (4.2%) but did not cause any hemodynamic instability.

Conclusion

When done with the necessary caution, dobutamine myocardial perfusion imaging is a safe diagnostic test, although side effects are common.     

Diagnostic utility of tomographic myocardial perfusion imaging with technetium 99m furifosmin (Q12) compared with thallium 201: Results of a phase III multicenter trial

Background  

Based on physical properties, ^99mTc-labeled perfusion agents offer several advantages over ²⁰¹Tl for myocardial perfusion imaging. The results of in vivo and experimental studies, along with preliminary experience in human subjects, have shown ^99mTc-labeled furifosmin to be a promising new perfusion tracer. The purpose of this study was to evaluate the safety of a new myocardial perfusion agent, ^99mTc-labeled furifosmin (Q12), and determine the concordance of furifosmin perfusion scintigraphy to ²⁰¹Tl imaging. In addition, we sought to determine the normalcy rate of myocardial scintigraphy with furifosmin.     

Detection of coronary artery disease: Comparison between technetium 99m-labeled sestamibi single-photon emission computed tomography and two-dimensional echocardiography with dipyridamole low-level exercise-stress

Background

Myocardial perfusion imaging in conjunction with dipyridamole low-level exercise stress has proved its value in the evaluation of patients with coronary artery disease (CAD). Simultaneous wall motion analysis by two-dimensional (2D) echocardiography may provide additional information beyond that obtained by myocardial perfusion imaging alone. The purpose of this study was to compare ^99mTc-labeled sestamibi single-photon emission computed tomography (SPECT) and 2D echocardiography for the evaluation of CAD according to a dipyridamole low-level bicycle exercise stress protocol.

Methods and Results

We studied 35 consecutive patients referred for the evaluation of chest pain who had undergone coronary arteriography. ^99mTc-labeled sestamibi SPECT and 2D echocardiography agreed in 27 patients (80%) studied for overall detection of CAD. On a segmental basis, agreement was found between SPECT and 2D echocardiography in 124 (73%) of 170 segments (Cohen’s kappa=0.43). The accuracy of the combined assessment of myocardial perfusion and echocardiographic wall motion in detecting CAD was 86%, which was not different from the accuracy of SPECT alone (80%; difference not significant) but significantly higher than for 2D echocardiography alone (71%; p=0.03). In the detection of individual coronary artery stenoses, SPECT had a significantly higher accuracy for detecting left anterior descending coronary artery lesions than had 2D echocardiography (80% vs 60%; p<0.01); combining the two methods did not improve the accuracy (80%). The combined assessment slightly improved the accuracy for detecting left circumflex coronary artery stenoses from 71% to 83% (p=0.05).

Conclusion

The combined simultaneous assessment of myocardial perfusion by ^99mTc-labeled sestamibi SPECT and wall motion by 2D echocardiography did not significantly improve overall accuracy over that obtained by ^99mTc-labeled sestamibi SPECT alone. Therefore ^99mTc-labeled sestamibi SPECT with dipyridamole low-level exercise stress appears the preferred imaging modality for the evaluation of patients with CAD.     

Comparative study of single-injection, single-acquisition 99mTc-MIBI gated SPET and stress-rest perfusion SPET for the evaluation of myocardial viability after bypass surgery in coronary artery disease

In patients without previous myocardial infarction, the single-injection stress perfusion/rest function (SISPRF) approach using stress technetium-99m methoxyisobutylisonitrile (MIBI) gated single-photon emission tomography (SPET) can substitute for conventional stress-rest myocardial perfusion imaging for the assessment of myocardial viability. This study compared pre-operative single-injection, single-acquisition ^99mTc-MIBI gated SPET and conventional stress-rest imaging for the prediction of myocardial viability in patients who underwent coronary artery bypass surgery (CABG). Rest thallium-201 SPET followed by stress ^99mTc-MIBI gated SPET was performed in 20 patients [nine with previous myocardial infarction (MI) and 11 without previous MI). The study was performed before and 3 months after CABG, and viability assessment was validated by wall motion improvement after CABG. A four-point scoring system (0-3 for normal to absent tracer uptake) for 17 segments of the left ventricular myocardium was used for the assessment of stress and rest uptake. Wall motion, wall thickening and perfusion status were analysed by semi-quantitative visual assessment. On gated SPET, perfusion defect reversibility was considered present when a definite perfusion defect was observed and wall motion or thickening was normal or showed only a mild decrease. In patients with a previous MI, the left ventricular ejection fraction improved significantly after CABG (46%lj% vs 42%ᆟ% before CABG, P<0.05). In patients without previous MI, the ejection fraction improved significantly after CABG (50ᆠ% vs 44%ᆤ% before CABG, P<0.05). In patients with previous MI, positive predictive values using the stress-rest reversibility and SISPRF approaches were 91% and 90%, respectively, and corresponding negative predictive values were 25% and 18%. In patients without previous MI, positive predictive values using the stress-rest and SISPRF approaches were 70% and 61%, respectively, and corresponding negative predictive values were 63% and 14%. It is concluded that SISPRF SPET study is of similar value to conventional stress-rest perfusion study in predicting wall motion improvement in patients with a previous MI, but that it is of limited value in predicting the myocardial viability of patients without previous MI, owing to a lower predictive value.     

Fluorine 18-labeled fluorodeoxyglucose myocardial single-photon emission computed tomography: An alternative for determining myocardial viability

The identification of hibernating myocardium in patients with poor ventricular function has become increasingly important as investigators demonstrate an improvement in ventricular performance in patients with injured but viable myocardium who undergo surgical revascularization. Modifications of ²⁰¹Tl redistribution protocols and rest/stress ^99mTc-labeled hexakis-2-methoxy-2-methyl propylisonitrile perfusion studies continue to underestimate myocardial viability compared with resting ¹⁸F-labeled fluorodeoxyglucose (¹⁸FDG) positron emission tomography. The combined data from multiple investigators suggest that ¹⁸FDG single-photon emission computed tomograpy used in combination with cardiac perfusion agents, either sequentially or with simultaneous dual-isotope acquisition, may provide an acceptable alternative to positron emission tomographic imaging for the detection of hibernating myocardium.     

Measurement of left ventricular ejection fraction from gated technetium-99m sestamibi myocardial images

Left ventricular ejection fraction (LVEF) and single-photon emission tomographic (SPET) imaging of the myocardium can be performed after a single technetium-99m sestamibi (MIBI) injection. Sixty patients underwent SPET imaging with MIBI. Immediately after SPET acquisition ECG-gated^99mTc-MIBI perfusion images were acquired using 24 planar images per R-R interval. A new method for measurement of LVEF from the ECG-gated 99mTc-MIBI perfusion images was developed. To validate the method, LVEF derived from MIBI perfusion images was compared with that from conventional radionuclide ventriculography in all 60 patients. Forty patients had evidence of myocardial infarction and 20 had normal perfusion on MIBI imaging. There was no statistically significant difference between LVEF computed from^99mTc-MIBI perfusion images and that from radionuclide ventriculography (r=0.7062,P<0.001). There was little difference associated with the technique (intraobserver variabilityr=0.9772,P<0.001). Interobserver variability was also good (r-0.8233,P<0.001). LVEF from^99mTc-MIBI perfusion images can be obtained at the same time as assessment of myocardial perfusion and in the same orientation and metabolism of the myocardium, thereby permitting more accurate and realistic prognosis and diagnosis in patients with coronary artery disease.     

Mechanism of uptake of technetium-tetrofosmin. I: Uptake into isolated adult rat ventricular myocytes and subcellular localization

Background

^99mTc-labeled tetrofosmin is a new myocardial imaging agent that gives stable heart uptake. However, little is known about the mechanism of uptake in heart tissue.

Methods and Results

Uptake of ^99mTc-labeled tetrofosmin has been examined in isolated adult rat ventricular myocytes. The time course of uptake, efflux rate, and the effect of metabolic and cation channel inhibitors have been assessed. The subcellular localization of radioactivity in ex vivo rat heart tissue was examined by differential centrifugation of ventricular homogenate. Uptake into rat myocytes was found to be rapid and plateaued at ?1.5 pmol/10⁶ cells/nmol extracellular Tc-labeled tetrofosmin after 60 minutes of incubation. Uptake was temperature dependent but independent of extracellular Tc-labeled tetrofosmin concentration. Uptake at 30 minutes was inhibited by the metabolic inhibitors iodoacetic acid acid and 2,4-dinitrophenol protein but was not affected by cation channel inhibitors. Cells previously incubated with ^99mTc-labeled tetrofosmin and then placed into fresh medium were found to have a slow efflux of activity; after 1 hour, 65% of activity was still cell associated. The localization of radioactivity in subcellular fractions indicated that the majority of activity was recovered with the cytosol. However, examination of the distribution of two mitochondrial enzymes indicated that this may have been artifactual. Use of carbonyl cyanide m-chlorophenyl-hydrazone or oligomycin to perturb mitochondrial membrane potential decreased or increased recovery in the mitochondrial fraction, respectively.

Conclusions

^99mTc-labeled tetrofosmin uptake by myocytes is by a metabolism-dependent process that does not involve cation channel transport. The most likely mechanism for this is by potential driven diffusion of the lipophilic cation across the sarcolemmal and mitochondrial membranes.     

Clearance of technetium 99m N-NOET in normal,ischemic-reperfused,and membrane-disrupted myocardium

Background

Technetium 99m-labeled bis (N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(v) (^99mTcN-NOET) is a new neutral cardiac perfusion imaging agent that has been shown to have very high uptake and retention in vitro. The purpose of this study was to determine the clearance kinetics of ^99m TcN-NOET in control, ischemic-reperfused, and membrane-disrupted myocardium.

Methods and Results

After a 100 μCi (3.7×10⁶ Bq) bolus of ^99mTcN-NOET was injected, myocardial clearance was monitored for 1 hour by the use of a sodium iodide detector in 30 isolated, Krebs-Henseleit (KH) perfused rat hearts. Seven hearts were used as controls (group 1). In seven ischemic-reperfused hearts, tracer administration and uptake was followed by 30 minutes of no flow and 1 hour of reflow (group 2). In six additional ischemic-reperfused hearts, tracer administration was followed by deprivation of flow for 1 hour followed by 1 hour of reflow (group 3). Six hearts were perfused with a 0.5% Triton X-100 KH perfusate for 1 hour (group 4). Four hearts were perfused with KH for 10 minutes, followed by cyanide for 10 minutes (group 5). This cycle was repeated three times. Activities remaining in each heart at the end of each experiment were quantitated, and activity at peak uptake was calculated. The ^99mTcN-NOET myocardial clearance was near linear in the control (0.6±0.4) and both ischemic-reperfused groups with virtually no fractional clearance (1.2%±0.6% and 2.1%±0.6%, respectively; p=NS). In the Triton X-100 membrane-disrupted hearts, clearance was substantial (94.2%±4.0%; p<0.0001 compared with the control and ischemic-reperfused groups). Cyanide treatment produced rapid clearance, which was arrested by a return to the standard KH perfusate. Peak uptake as a percentage of injected dose was 74.9%±1.4% for all groups combined.

Conclusion

Thus ^99mTcN-NOET has extremely high myocardial retention after 1 hour in normal myocardium and is not significantly affected by ongoing myocardial ischemia or reperfusion injury in this model. Clearance is increased markedly in extreme conditions of membrane disruption. These data are consistent with the concept that ^99mTc-NOET is localized predominantly in or on cell membranes. ^99mTcN-NOET is a promising, new myocardial perfusion imaging agent that exhibits a stable myocardial distribution in the setting of acute developing injury.     

Regional heterogeneity in cardiac sympathetic innervation in acute myocardial infarction: relationship with myocardial oedema on magnetic resonance

Purpose

To assess the relationships between myocardial structure and function on cardiac magnetic resonance (CMR) imaging and sympathetic tone on ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy early after myocardial infarction (MI).

Methods

Ten patients underwent ¹²³I-MIBG and ^99mTc-tetrofosmin rest cadmium zinc telluride scintigraphy 4?±?1 days after MI. The segmental left ventricular (LV) relative radiotracer uptake of both ^99mTc-tetrofosmin and early ¹²³I-MIBG was calculated. The day after scintigraphy, on CMR imaging, the extent of ischaemia-related oedema and of myocardial fibrosis (late gadolinium enhancement, LGE) was assessed. Accordingly, the extent of oedema and LGE was evaluated for each segment and segmental wall thickening determined. Based on LGE distribution, LV segments were categorized as "infarcted" (56 segments), "adjacent" (66 segments) or "remote" (48 segments).

Results

Infarcted segments showed a more depressed systolic wall thickening and greater extent of oedema than adjacent segments (p?<?0.001) and remote segments (p?<?0.001). Interestingly, while uptake of ^99mTc-tetrofosmin was significantly depressed only in infarcted segments (p?<?0.001 vs. both adjacent and remote segments), uptake of ¹²³I-MIBG was impaired not only in infarcted segments (p?<?0.001 vs. remote) but also in adjacent segments (p?=?0.024 vs. remote segments). At the regional level, after correction for ^99mTc-tetrofosmin and LGE distribution, segmental ¹²³I-MIBG uptake (p?<?0.001) remained an independent predictor of ischaemia-related oedema.

Conclusion

After acute MI the regional impairment of sympathetic tone extends beyond the area of altered myocardial perfusion and is associated with myocardial oedema.     

Resting technetium-99m methoxyisobutylisonitrile cardiac imaging in chronic coronary artery disease: comparison with rest-redistribution thallium-201 scintigraphy

We studied 19 patients with angiographically proven coronary artery disease and left ventricular dysfunction (ejection fraction 33% ± 8%) by resting technetium-99m methoxyisobutylisonitrile (^99mTc-MIBI) and rest-redistribution thallium-201 cardiac imaging. Thallium and (^99mTc-MIBI) studies were visually analysed. Of 285 segments, 203 (71%) had normal thallium uptake, 48 (17%) showed reversible thallium defects and 34 (12%) showed irreversible thallium defects. Of these 34 irreversible thallium defects, 19 (56%) were moderate and 15 (44%) were severe. Of the corresponding 285 segments, 200 (70%) had normal ^99mTc-MIBI uptake, while 37 (13%) showed moderate and 48 (17%) showed severe reduction of 99 ^99mTc-MIBI uptake. Myocardial segmental agreement for regional uptake score between initial thallium and resting (^99mTc-MIBI) images was 90% (=0.78). Segmental agreement between delayed thallium and resting ⁹⁹Tc-MIBI images was 77% (=0.44). In particular, in 26 (9%) segments ^99mTc-MIBI uptake was severely reduced while delayed thallium uptake was normal or only moderately reduced. These data suggest that although rest-redistribution thallium and resting (^99mTc-MIBI) cardiac imaging provide concordant results in the majority of myocardial segments, some segments with severely reduced resting ^99mTc-MIBI uptake may contain viable but hypoperfused myocardium. Thus, conclusions on myocardial viability based on ^99mTc-MIBI uptake should be made with caution in chronic coronary artery disease.     

Reduced variability of interpretation and improved image quality with a technetium 99m myocardial perfusion agent: Comparison of thallium 201 and technetium 99m-labeled tetrofosmin

Background  

The purpose of this study was to determine the relative image quality and interobserver variability among four readers for²⁰¹Tl and^99mTc-labeled tetrofosmin myocardial perfusion images.^99mTc-labeled perfusion agents, with near-optimal physical characteristics for gamma camera imaging, may allow for superior image quality and improved consistency of interpretation. However, most studies to date have demonstrated only similarity in the diagnostic accuracy between technetium agents and thallium. Tetrofosmin is a recently developed^99mTc-labeled agent that has shown promising results in early clinical trials.