Prognostic value of dobutamine stress technetium-99m-sestamibi single-photon emission computed tomography myocardial perfusion imaging: stratification of a high-risk population.

OBJECTIVES: This work was undertaken to define the intrinsic cardiac risk of the patient population referred for dobutamine stress perfusion imaging and to determine whether dobutamine technetium-99m ((99m)Tc)-sestamibi single-photon emission computed tomography (SPECT) imaging is capable of risk stratification in this population. BACKGROUND: In animal models, dobutamine attenuates the myocardial uptake of (99m)Tc-sestamibi resulting in underestimation of coronary stenoses. Therefore, we hypothesized that the prognostic value of dobutamine stress (99m)Tc-sestamibi SPECT myocardial perfusion imaging might be impaired, owing to reduced detection of coronary stenoses. METHODS: We reviewed the clinical outcome of 308 patients (166 women, 142 men) who underwent dobutamine stress SPECT (99m)Tc-sestamibi imaging at our institution from September 1992 through December 1996. RESULTS: During an average follow-up of 1.9 +/- 1.1 years, there were 33 hard cardiac events (18 myocardial infarctions [MI] and 15 cardiac deaths) corresponding to an annual cardiac event rate of 5.8%/year, which is significantly higher than the event rate for patients referred for exercise SPECT imaging at our institution (2.2%/year). Event rates were higher after an abnormal dobutamine (99m)Tc-sestamibi SPECT study (10.0%/year) than after a normal study (2.3%/year) (p < 0.01), even after adjusting for clinical variables. In the subgroup (n = 29) with dobutamine-induced ST-segment depression and abnormal SPECT imaging, the prognosis was poor, with annual cardiac death and nonfatal MI rates of 7.9% and 13.2%, respectively. CONCLUSIONS: Patients referred for dobutamine perfusion imaging are a high-risk population, and dobutamine stress (99m)Tc-sestamibi SPECT imaging is capable of risk stratification in these patients.

Pharmacological stress myocardial perfusion imaging with the potent and selective A(2A) adenosine receptor agonists ATL193 and ATL146e administered by either intravenous infusion or bolus injection.

BACKGROUND: Adenosine (Ado) and dipyridamole are alternatives to exercise stress for myocardial perfusion imaging. Though generally safe, side effects frequently occur that cause patient discomfort and sometimes lead to premature termination of the study or require aminophylline administration. Recently, a new class of A(2A) Ado receptor agonists was synthesized. ATL193 and ATL146e are 2-propynylcyclohexyl-5'-N-ethylcarboxamido derivatives of Ado. The study goals were to evaluate the potency and selectivity of these new compounds on recombinant canine Ado receptors and to evaluate their hemodynamic properties in dogs to assess their usefulness as vasodilators for myocardial perfusion imaging. METHODS AND RESULTS: In assays of recombinant canine Ado receptors, ATL-193 and ATL-146e were highly selective for the A(2A) over the A(1) and A(3) receptors and were more potent than MRE-0470 and CGS-21680. In 16 anesthetized dogs, the agonists were administered by infusion (ATL-193; n=7 normal) or bolus injection (ATL-146e; n=9 critical left anterior descending coronary artery stenosis), and hemodynamic responses were compared with those of Ado. Both agonists produced dose-dependent coronary flow (CF) elevation without provoking the hypotension observed with Ado. After an ATL-146e bolus, the CF increase was sustained for several minutes, providing ample time for injection and myocardial uptake of (99m)Tc-sestamibi, and CF returned to baseline within 20 minutes. The CF increase was completely blocked by the selective A(2A) antagonist ZM241385 (3 microgram. kg(-1). min(-1)). CONCLUSIONS: ATL-193 and ATL-146e are highly potent and selective Ado A(2A) receptor agonists with excellent potential for use as vasodilators for myocardial perfusion imaging. An important advantage of ATL-146e is the ability to administer it by bolus injection.

Assessment of residual coronary stenoses using 99mTc-N-NOET vasodilator stress imaging to evaluate coronary flow reserve early after coronary reperfusion in a canine model of subendocardial infarction.

UNLABELLED: Reperfusion is often incomplete after recanalization therapy because of the presence of residual coronary stenoses. Detecting mild to moderate stenoses requires assessing coronary flow reserve with vasodilator stress. 99mTc-(N-ethoxy-N-ethyl-dithiocarbamato)nitrido (N-NOET) is a viability-independent flow tracer and thus may be well suited for assessing coronary flow reserve in the acute phase of reperfusion. METHODS: Twelve open-chest dogs underwent 60 min of total left anterior descending artery (LAD) occlusion followed by either full reperfusion (group 1; n = 4) or reperfusion through a residual critical stenosis (group 2; n = 8). 99mTc-N-NOET was given during peak vasodilator stress 165 min after reperfusion, and initial and 60-min delayed images were acquired. Regional blood flow was assessed with radiolabeled microspheres. RESULTS: Infarct size was similar in both groups (9% +/- 2% vs. 8% +/- 2% of left ventricle). Both initial (0.61 +/- 0.02 vs. 0.73 +/- 0.01; P < 0.01) and 60-min (0.67 +/- 0.02 vs. 0.80 +/- 0.01; P < 0.01) defect count ratios (LAD/left circumflex coronary artery [LCx]) differentiated between the 2 groups, reflecting the greater diminution in coronary flow reserve in group 2 dogs (LAD/LCx flow ratios = 0.37 +/- 0.04 vs. 0.57 +/- 0.09; P < 0.01). Interestingly, coronary flow reserve in the reperfused zone of group 1 was diminished despite the absence of a stenosis. Thus, the difference in 99mTc-N-NOET uptake between the 2 groups was less than expected. CONCLUSION: In this canine myocardial infarction model with some coronary flow reserve preservation, 99mTc-N-NOET imaging can detect residual coronary stenoses. However, with more prolonged occlusion resulting in more severe endothelial or microvascular dysfunction, it may be difficult to distinguish varying degrees of vessel patency using any coronary flow reserve technique.

Tc-99m sestamibi defect magnitude predicts the amount of viable myocardium after coronary reperfusion despite the presence of severe residual stenosis.

BACKGROUND: Whether technetium-99m-labeled methoxyisobutyl isonitrile (Tc-99m sestamibi) imaging early after reperfusion can detect the amount of salvaged viable myocardium in the presence of a severe residual stenosis remains controversial. METHODS AND RESULTS: Nine dogs underwent total left anterior descending coronary artery (LAD) occlusion for 40 to 180 minutes followed by reperfusion through a flow-limiting stenosis. They were divided into 2 groups based on infarct size (group 1, <15% of risk area; group 2, > or =15%). Triphenyl tetrazolium chloride infarct size was measured by planimetry, and regional flow was quantified by radiolabeled microspheres. Mean infarct size was 9.3% +/- 3.0% of risk area in group 1 versus 51.1% +/- 4.8% in group 2 (P <.01). Tc-99m sestamibi was injected 30 minutes after reperfusion, when the LAD flows were comparable for group 1 (9 +/- 2 mL. min(-1)) and group 2 (9 +/- 1 mL. min(-1)). Left circumflex coronary artery flows were 33 +/- 5 and 32 +/- 9 mL. min(-1) for groups 1 and 2, respectively. Despite administration of Tc-99m sestamibi during diminished residual LAD flow after reperfusion, defect magnitude on ex vivo images in group 1 was significantly less severe than that in group 2, which had larger infarcts (0.71 +/- 0.02 vs 0.42 +/- 0.05, P <.01). This reflects greater salvage and more viability in group 1. CONCLUSION: Resting perfusion imaging with Tc-99m sestamibi accurately determined viability of the infarct zone despite reperfusion through a residual stenosis. Tc-99m sestamibi imaging may prove useful in the clinical setting for the prediction of the amount of salvaged myocardium.

Response to incremental doses of dobutamine early after reperfusion is predictive of the degree of myocardial salvage in dogs with experimental acute myocardial infarction.

OBJECTIVES: We sought to determine whether the inotropic response to dobutamine might be useful for estimating the extent of viable myocardium soon after reperfusion. BACKGROUND: Early identification of viable myocardium in the presence of severe left ventricular dysfunction after reperfusion is important for clinical decision making. METHODS: Nine open-chest dogs had left anterior descending coronary artery occlusion for 40 to 180 min, followed by gradual reperfusion. The systolic thickening response to incremental dobutamine doses was measured with ultrasonic crystals and regional flow by microspheres. RESULTS: Dogs were divided into two groups based on triphenyl tetralozium chloride infarct size (group 1: 9.3 +/- 3.0% risk area; group 2: 51.1 +/- 4.8%). In group 2 dogs with larger infarcts, regional flow during peak dobutamine was lower than it was in group 1 in endocardial (1.15 +/- 0.22 vs. 2.64 +/- 0.33 mL x min(-1) x g(-1)) and midwall (1.47 +/- 0.32 vs. 2.92 +/- 0.36 mL x min(-1) x g(-1)) layers, and endocardial flow in group 2 failed to increase from baseline (0.96 +/- 0.07 vs. 1.15 +/- 0.22 mL x min(-1) x g(-1)). Group 1 dogs demonstrated a dose dependent increase in systolic thickening with dobutamine versus a blunted response in group 2. The inotropic response to only 10 microg x kg(-1) x min(-1) of dobutamine was predictive of the degree of myocardial salvage. CONCLUSIONS: In the early postischemic stunning phase of reperfusion, the inotropic response to dobutamine is predictive of the degree of myocardial salvage and ultimate infarct size. The ability to distinguish between stunned versus necrotic myocardium early after reperfusion was most likely due to the presence of subendocardial flow reserve during dobutamine in dogs with predominantly salvaged myocardium.

Optimal timing for initial and redistribution technetium 99m-N-NOET image acquisition.

BACKGROUND: Bis (N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium-99m (V) (Tc-99m-N-NOET) is a new Tc-99m-labeled myocardial perfusion imaging agent that redistributes. We sought to determine the optimal timing for acquiring initial and delayed images to maximize sensitivity for the detection of coronary stenoses. METHODS: Twelve anesthetized dogs with critical stenoses of the left anterior descending coronary artery were infused with adenosine (250 microg/kg/min) or MRE-0470, an adenosine A2a agonist (0.6 microg/kg/min x 10 minutes), and Tc-99m-N-NOET (8 mCi; 296 MBq) was injected intravenously at peak flow. Myocardial and lung Tc-99m-N-NOET activities were determined by serial quantitative imaging and arterial blood sampling was performed over 2 hours. RESULTS: Left anterior descending/left circumflex artery defect count ratios showed rapid redistribution during the first 10 minutes after Tc-99m-N-NOET injection (0.66 +/- 0.02 at 2 minutes to 0.73 +/- 0.01 at 10 minutes; P < .01). Redistribution was nearly complete by 120 minutes (defect ratio = 0.87 +/- 0.03; P < or = .01 vs 2 minutes). Lung activity fell significantly during the first 10 minutes from a heart/lung activity ratio of 1.07 +/- 0.05 (2 minutes) to 1.44 +/- 0.09 (10 minutes; P < or = .01). CONCLUSION: Initial stress Tc-99m-N-NOET images should be acquired within 10 minutes after injection, whereas delayed images can be obtained as early as 2 hours later. Lung activity clears rapidly, permitting acquisition of good-quality poststress cardiac images. These Tc-99m-N-NOET uptake and redistribution kinetics after vasodilator stress provide important information for designing clinical imaging protocols for optimal identification of inducible ischemia.

99mTc-N-NOET myocardial uptake reflects myocardial blood flow and not viability in dogs with reperfused acute myocardial infarction.

BACKGROUND: N-Ethoxy-N-ethyl-dithiocarbamato-nitrido-(99m)Tc ((99m)Tc-N-NOET) is a new neutral lipophilic (99m)Tc-labeled myocardial perfusion agent with a high first-pass extraction fraction and delayed redistribution kinetics after transient ischemia comparable to what is observed with (201)Tl. It is unknown whether the uptake of this tracer reflects myocardial viability or just reperfusion flow in the setting of a reperfused myocardial infarction. METHODS AND RESULTS: In 13 anesthetized open-chest dogs, the left anterior descending coronary artery was occluded for 180 minutes, followed by 180 minutes of reperfusion. (201)Tl and (99m)Tc-N-NOET were injected after either 60 (group 1, n=9) or 175 (group 2, n=4) minutes of reperfusion. Myocardial blood flow was measured by radioactive microspheres, and (201)Tl and (99m)Tc-N-NOET tissue activities were determined by gamma-well counting. Normalized myocardial blood flow in the central infarct zone fell from 0.80+/-0. 03 (SEM) and 0.89+/-0.01 at baseline to 0.18+/-0.04 and 0.13+/-0.02 during the occlusion in groups 1 and 2, respectively. Normalized (201)Tl activity in these segments was 0.39+/-0.04 and 0.43+/-0.04 and reflected myocardial viability rather than reperfusion flow (P<0. 001). Normalized (99m)Tc-N-NOET activity in the same segments was 0. 84+/-0.08 and 0.64+/-0.03, respectively (P<0.01 versus (201)Tl; P=NS versus reperfusion flow) and more accurately reflected reperfusion flow (0.99+/-0.17 and 0.70+/-0.04) than residual viability. CONCLUSIONS: The myocardial uptake of (99m)Tc-N-NOET reflects reperfusion myocardial blood flow and not viability in a canine model of reperfused acute myocardial infarction. The clinical use of early (99m)Tc-N-NOET imaging to assess the success of coronary reperfusion in patients with acute myocardial infarction should be investigated.

Myocardial uptake of (99m)Tc-N-NOET and (201)Tl during dobutamine infusion. Comparison with adenosine stress.

BACKGROUND: The myocardial uptake of (99m)Tc-sestamibi is attenuated by dobutamine stress, resulting in underestimation of ischemia. N-Ethyl-N-ethoxy-dithiocarbamato-N-(99m)Tc ((99m)Tc-N-NOET) is a new (99m)Tc-labeled perfusion agent that is highly extracted by the myocardium by a mechanism different from that defined for (99m)Tc-sestamibi. We therefore hypothesized that (99m)Tc-N-NOET uptake would not be attenuated by dobutamine and that (99m)Tc-N-NOET uptake would be comparable to (201)Tl uptake during dobutamine stress. METHODS AND RESULTS: In 28 open-chest dogs, after placement of a stenosis in the left anterior descending coronary artery that reduced flow reserve by >50%, adenosine (300 microgram. kg(-1). min(-1); n=15) or dobutamine (2.5 to 30 microgram. kg(-1). min(-1); n=13) was infused. During adenosine stress, the stenotic-to-normal activity ratio for (99m)Tc-N-NOET was 0.55+/-0.05. The stenotic-to-normal flow ratio was 0.33+/-0.04 at the time of (99m)Tc-N-NOET injection. During dobutamine stress, the stenotic-to-normal (99m)Tc-N-NOET activity ratio was 0.63+/-0.04, comparable to the (201)Tl activity ratio of 0.59+/-0.04. The stenotic-to-normal flow ratio was 0.47+/-0.04 at the time of (99m)Tc-N-NOET and (201)Tl injection. The relationship between (99m)Tc-N-NOET uptake and blood flow was comparable for adenosine and dobutamine stress, with no evidence of attenuation of (99m)Tc-N-NOET extraction by dobutamine. Conclusions-In the presence of coronary stenoses that reduced regional flow reserve, the myocardial uptake of (99m)Tc-N-NOET and (201)Tl are closely proportional to blood flow during both adenosine and dobutamine stress, suggesting that the adverse effect of dobutamine on (99m)Tc-sestamibi uptake is a tracer-specific phenomenon rather than a generalized effect. The clinical implication of this finding is that (99m)Tc-N-NOET might be preferable to (99m)Tc-sestamibi when used with dobutamine stress for detection of coronary stenoses.

Quantitative SPECT techniques.

Quantitative imaging involves first, a set of measurements that characterize an image. There are several variations of technique, but the basic measurements that are used for single photon emission computed tomography (SPECT) perfusion images are reasonably standardized. Quantification currently provides only relative tracer activity within the myocardial regions defined by an individual SPECT acquisition. Absolute quantification is still a work in progress. Quantitative comparison of absolute changes in tracer uptake comparing a stress and rest study or preintervention and postintervention study would be useful and could be done, but most commercial systems do not maintain the data normalization that is necessary for this. Measurements of regional and global function are now possible with electrocardiography (ECG) gating, and this provides clinically useful adjunctive data. Techniques for measuring ventricular function are evolving and promise to provide clinically useful accuracy. The computer can classify images as normal or abnormal by comparison with a normal database. The criteria for this classification involve more than just checking the normal limits. The images should be analyzed to measure how far they deviate from normal, and this information can be used in conjunction with pretest likelihood to indicate the level of statistical certainty that an individual patient has a true positive or true negative test. The interface between the computer and the clinician interpreter is an important part of the process. Especially when both perfusion and function are being determined, the ability of the interpreter to correctly assimilate the data is essential to the use of the quantitative process. As we become more facile with performing and recording objective measurements, the significance of the measurements in terms of risk evaluation, viability assessment, and outcome should be continually enhanced.

Assessment of myocardial viability using 123I-labeled iodophenylpentadecanoic acid at sustained low flow or after acute infarction and reperfusion.

UNLABELLED: 123I-labeled iodophenylpentadecanoic acid (IPPA) is a synthetic fatty acid that may be useful for determination of myocardial viability. We investigated the uptake and clearance kinetics of this tracer in canine models of ischemia and infarction. METHODS: In protocol 1, 185 MBq (5 mCi) 123I-IPPA were injected intravenously in 19 dogs with 50% left anterior descending artery (LAD) flow reduction. In 9 dogs, 201TI was coinjected. In protocol 2, 5 dogs underwent LAD occlusion for 3 h, and 123I-IPPA was injected 60 min after reperfusion. All dogs had flow measured by microspheres, regional systolic thickening by ultrasonic crystals and measurements of postmortem risk area and infarct size. Tracer activities were quantified by gamma well counting and by serial imaging. RESULTS: In protocol 1 dogs with sustained low flow (50% +/- 4%) and absence of systolic thickening (-3.2% +/- 1%), 123I-IPPA defect magnitude (LAD/left circumflex artery [LCX] count ratios) decreased from 0.65 +/- 0.02 to 0.74 +/- 0.02 at 30 min and to 0.84 +/- 0.03 at 2 h (P < 0.01), indicative of rest redistribution. Final transmural 123I-IPPA LAD/LCX activity ratio (0.99 +/- 0.05) was significantly greater than the flow ratio (0.53 +/- 0.04) at injection, confirming complete rest redistribution. The final 123I-IPPA activity ratio was significantly greater than the 201TI ratio over the 2-h period (P < 0.01). In protocol 2 dogs that underwent 3 h of total LAD occlusion and reflow (infarct size = 51% +/- 13% of risk area), viability was overestimated with 123I-IPPA, because uptake averaged 64% of normal in the central necrotic region, where flow averaged < 10% of normal. CONCLUSION: These findings suggest that serial 123I-IPPA imaging may be useful for assessing myocardial viability under conditions of sustained low flow and myocardial asynergy, such as appears to exist in patients with chronic coronary artery disease and depressed left ventricular function. In contrast, 123I-IPPA given early after reperfusion following prolonged coronary occlusion overestimates the degree of viability and therefore may not provide useful information pertaining to the degree of myocardial salvage after reflow in the setting of acute myocardial infarction.

99mTc-tetrofosmin assessment of myocardial perfusion and viability in canine models of coronary occlusion and reperfusion.

UNLABELLED: The goal of this study was to determine whether 99mTc-tetrofosmin can assess regional flow heterogeneity when injected during sustained coronary artery occlusion and to estimate the degree of myocardial salvage and viability during coronary reperfusion. METHODS: In protocol 1, 99mTc-tetrofosmin, 201 TI and microspheres were injected during total left anterior descending (LAD) coronary artery occlusion in five anesthetized open-chested dogs. Protocol 2 dogs underwent LAD occlusion for either 60 min (n = 7) or 180 min (n = 6) followed by 105 min of reperfusion. 99mTc-tetrofosmin (10 mCi), 201TI (1 mCi) and microspheres were injected 90 min after reflow. In both protocols, myocardial 99mTc-tetrofosmin and 201TI activities were quantified from regions of interest on ex vivo images and by in vitro well counting. RESULTS: In protocol 1, there was a linear relationship between 201TI (r = 0.96) and 99mTc-tetrofosmin (r 0.92) activities and microsphere flow during the occlusion. In protocol 2, the LAD/left circumflex (LCx) defect count ratios for 99mTc-tetrofosmin and 201TI from images of myocardial slices were comparable in dogs undergoing either 1 or 3 h of LAD occlusion and 105 min of reperfusion. Similarly, the LAD/LCx in vitro count ratios were comparable between 201TI and 99mTc-tetrofosmin in 1 and 3 h occluded dogs, and significantly lower than the reperfusion flow when these tracers were injected. Uptake of both tracers was depressed to a greater extent in areas of severe ischemic damage. CONCLUSION: These data suggest that administration of 99mTc-tetrofosmin during coronary occlusion accurately delineates the flow heterogeneity. When given after reperfusion, 99mTc-tetrofosmin uptake was significantly reduced in reperfused, infarcted areas and was reflective of viability and the degree of myocardial salvage in addition to reperfusion flow. These experimental studies validate the clinical use of 99mTc-tetrofosmin for assessing persistent coronary artery occlusion, and infarct size and myocardial viability after reperfusion.

Safety assessment of enzyme-containing personal cleansing products: exposure characterization and development of IgE antibody to enzymes after a 6-month use test.

BACKGROUND: Enzyme-containing personal cleansing products were being considered for the consumer market. Although enzymes have been marketed safely for many years as ingredients in laundry products, their use in a personal cleansing application represented a new type of exposure for consumers that was not supported by the historical safety data. An exposure assessment and additional safety data would be needed before marketing to ensure consumer safety. OBJECTIVE: The work in this paper was designed to evaluate the potential for inhalation exposure to the enzyme during use of this new product while showering. Then a clinical trial was conducted to determine whether or not the level, duration, and routes of exposure encountered during use of this product would induce a Type I sensitization response to the enzyme. METHODS: Exposure was assessed during normal showering activities by collecting air samples with both high volume and personal samplers and quantitating enzyme levels with an ELISA. To assess the potential for sensitization, panelists were asked to use a prototype protease-containing bar product for all personal cleansing tasks and to keep a use diary reporting any associated symptoms. Physical and dermatologic examinations and skin prick tests with enzyme were conducted before the test commenced and at 2-month intervals. RESULTS: Exposure assessment results showed that airborne enzyme levels were primarily dependent on the concentration of the enzyme in the personal cleansing product. Mean values for total airborne enzyme protein ranged from 5.7 to 11.8 ng/m3 when enzyme concentration, time of use, and measurement technique remained constant. After 6 months of at-home product use, four of 61 test subjects using the enzyme-containing bar had positive skin prick test responses when tested with the enzyme. The skin prick test data were supplemented with serologic analyses, which detected IgE specific for the protease enzyme. None of these subjects showed any clinical symptoms indicative of allergic reaction. CONCLUSION: The ability of enzymes to induce development of allergic antibodies in this study led to the conclusion that this prototype enzyme-containing personal cleansing bar would represent an inappropriate use of enzymes in a consumer product application. The likelihood of both induction of an immunologic response and subsequent elicitation of allergy symptoms in a small but significant fraction of the user population was high. This finding resulted in the decision to halt further development of this prototype.

Comparison of technetium-99m tetrofosmin and thallium-201 single-photon emission computed tomographic imaging for detection of myocardial perfusion defects in patients with coronary artery disease.

OBJECTIVES: We compared dipyridamole technetium-99m (Tc-99m) tetrofosmin and thallium-201 (Tl-201) single-photon emission computed tomographic (SPECT) imaging with respect to the detection rate of perfusion abnormalities in 26 patients with angiographic coronary artery disease (CAD). BACKGROUND: Experimental studies have shown that myocardial extraction of Tc-99m tetrofosmin is lower than that of Tl-201 at high flow rates, resulting in less severe defects with vasodilator stress. It is uncertain whether this results in a lower sensitivity than Tl-201 for detecting coronary stenoses with vasodilator stress in patients. METHODS: Twenty-six patients with CAD underwent both dipyridamole Tl-201 and Tc-99m tetrofosmin SPECT. Tomographic images were scored for initial defects and the presence of reversibility. Defect magnitude was computer quantitated. RESULTS: Of the 26 patients, 25 had defects on both Tl-201 and Tc-99m tetrofosmin SPECT images. Of 340 segments analyzed, 102 had defects by Tl-201 and 92 by Tc-99m tetrofosmin (p = NS). Whereas Tl-201 detected 27 fixed defects in 12 patients, Tc-99m tetrofosmin identified 37 fixed defects in 14 patients (p = NS). In contrast, Tl-201 identified more reversible and partially reversible defects than did Tc-99m tetrofosmin (89 vs. 55, p = 0.002). The average defect magnitude (percent normal) was similar for defects concordantly graded as fixed (38 +/- 3.0% for Tl-201 vs. 42 +/- 4% [mean +/- SEM] for Tc-99m tetrofosmin, p = NS). The average defect magnitude for defects concordantly graded as completely reversible was significantly more severe on Tl-201 than on Tc-99m tetrofosmin (49 +/- 3% vs. 58 +/- 3%) SPECT images. A significantly greater defect magnitude for Tl-201 was also found for defects concordantly classified as partly reversible (30 +/- 4% for Tl-201 vs. 45 +/- 5% for Tc-99m tetrofosmin). CONCLUSIONS: With dipyridamole stress, 1) at least one defect was seen on both Tl-201 and Tc-99m tetrofosmin SPECT images; 2) Tc-99m tetrofosmin SPECT identified fewer reversible defects than did Tl-201, but showed a similar number of fixed defects; 3) the magnitude of reversible defects seen on Tc-99m tetrofosmin images was less, whereas fixed defects were similar for both tracers; 4) reversible defects seen on Tl-201 and not on Tc-99m tetrofosmin SPECT images were predominantly regions perfused by mild coronary stenoses.

Value of gating of technetium-99m sestamibi single-photon emission computed tomographic imaging.

OBJECTIVES: The purpose of this study was to determine how frequently and for what reasons the addition of electrocardiographically gated technetium-99m (Tc-99m) sestamibi single-photon emission computed tomographic (SPECT) images add value to nongated SPECT perfusion images. BACKGROUND: Electrocardiographic gating of Tc-99m sestamibi SPECT images permits assessment of regional and global left ventricular function and may assist in differentiating attenuation artifacts from myocardial scar. METHODS: A total of 285 consecutive patients (143 women and 142 men; mean age 57.6 +/- 11.5 years) underwent gated SPECT Tc-99m sestamibi imaging (212 with exercise, 63 with dipyridamole and 10 with dobutamine). The conventional stress and rest tomograms were interpreted first by means of a 14-segment scoring system, and then the studies were reinterpreted while the gated images were viewed. RESULTS: In the total group of 285 patients, the number of "borderline" interpretations was reduced from 89 to 29. In the 137 patients with a < or = 10% pretest likelihood of coronary artery disease, the addition of gated images added significantly to the percentage of interpretations that were designated "normal" (74% [101 of 137] vs. 93% [127 of 137], p < 0.0001), due to a reduction in borderline normal and borderline abnormal readings. In 49 patients with a previous infarction or recent angiography with > or = 70% stenosis, or both, the addition of gated images changed the percentage of "abnormal" scan interpretations from 78% (38 of 49) to 92% (45 of 49). This result was not significant (p = 0.09, two-tailed), but the trend was toward a greater number of unequivocal abnormal interpretations in this subgroup. CONCLUSIONS: The addition of electrocardiographically gated Tc-99m sestamibi SPECT images to the reading of stress and rest perfusion images alone resulted in shifting the final scan interpretations to a more normal designation in patients with a low pretest likelihood of coronary artery disease, and to more abnormal defects consistent with coronary artery disease in patients with known coronary artery disease. The number of "borderline normal" and "borderline abnormal" interpretations are significantly reduced when gated SPECT images are interpreted simultaneously with stress and rest perfusion images.

Myocardial uptake and redistribution of 99mTc-N-NOET in dogs with either sustained coronary low flow or transient coronary occlusion: comparison with 201Tl and myocardial blood flow.

BACKGROUND: 99mTc-N-NOET (NOET) is a new myocardial perfusion imaging agent that redistributes over time. We sought to better define the redistribution kinetics of NOET using open-chest canine models of sustained low coronary flow (protocol 1) and transient coronary occlusion followed by reflow (protocol 2). METHODS AND RESULTS: In protocol 1 (n=10), NOET and 201Tl were injected during low flow in the left anterior descending coronary artery (LAD) that was sustained for 2 hours. Protocol 2 dogs (n=6) were injected with NOET during 20 minutes of LAD occlusion followed by 2 hours of reflow. In both protocols, serial NOET planar images were acquired, and myocardial flow and 2-hour tracer activities were determined by gamma-well counting. Defect resolution was observed on images in both protocols. Initial defect count ratios, reflecting flow disparity at injection (0.66+/-0.03 and 0.57+/-0.04, respectively), increased over 2 hours (0.73+/-0.02 and 0.75+/-0.04, respectively; P<.001 versus initial). Quantitative imaging showed that NOET redistribution resulted from greater clearance from normal areas versus low-flow or transiently occluded areas. In protocol 1, 2-hour NOET and 201Tl stenotic-to-normal tissue activity ratios were similar (0.76+/-0.06 versus 0.73+/-0.04, P=NS) and higher than injection flow ratios (0.52+/-0.06 and 0.56+/-0.07, respectively, P<.001), consistent with tracer redistribution. In protocol 2, NOET redistributed to an even greater extent (injection flow ratio, 0.27+/-0.04; 2-hour tissue activity ratio, 0.84+/-0.03, P<.001). CONCLUSIONS: NOET is the first 99mTc-labeled myocardial imaging agent with kinetics similar to 201Tl in experimental models, permitting redistribution imaging. NOET appears to be a promising agent for assessing patients with coronary artery disease.

Myocardial 99mTc-tetrofosmin uptake during adenosine-induced vasodilatation with either a critical or mild coronary stenosis: comparison with 201Tl and regional myocardial blood flow.

BACKGROUND: Clinical studies have shown a comparable coronary stenosis detection rate between 99mTc-tetrofosmin and 201Tl but with smaller defect magnitudes for 99mTc-tetrofosmin. The goals of this study were to measure the first-pass extraction fraction (EF) of 99mTc-tetrofosmin in canine myocardium and to compare 99mTc-tetrofosmin with 201Tl uptake during adenosine-induced vasodilatation in dogs with various degrees of coronary stenosis. METHODS AND RESULTS: EF was calculated in 4 anesthetized, open-chest dogs after intracoronary administration of 125I-labeled albumin and 99mTc-tetrofosmin. In another 16 dogs with either critical (n=6) or mild (n= 10) left anterior descending coronary artery (LAD) stenoses, 201Tl and 99mTc-tetrofosmin were administered during adenosine infusion (250 microg x kg(-1) x min(-1)). Dogs were killed 5 minutes later, and tracer activities were determined by ex vivo imaging of heart slices and by well counting. Mean 99mTc-tetrofosmin EF was 54.0+/-3.7%. In the 6 critical-stenosis dogs, the LAD-to-left circumflex artery (LCx) microsphere flow ratio was 0.22+/-0.02 with adenosine. The LAD-to-LCx activity ratios were 0.37+/-0.04 for 201Tl and 0.67+/-0.05 for 99mTc-tetrofosmin (P<.01). For the 10 mild-stenosis dogs, the LAD-to-LCx flow ratio was 0.44+/-0.05. The 201Tl activity ratio was 0.58+/-0.04, compared with 0.81+/-0.04 for 99mTc-tetrofosmin (P<.01). Thus, in both groups, 99mTc-tetrofosmin uptake underestimated the flow disparity more than 201Tl. Similarly, magnitudes of ex vivo image defects were significantly greater for 201Tl than for 99mTc-tetrofosmin in both groups. CONCLUSIONS: In this canine model, relative underperfusion with adenosine stress is better resolved with 201Tl than with 99mTc-tetrofosmin and may be explained by the lower EF for 99mTc tetrofosmin. With clinical imaging, greater 201Tl attenuation and redistribution may lessen this advantage.

Effects of dobutamine stress on myocardial blood flow, 99mTc sestamibi uptake, and systolic wall thickening in the presence of coronary artery stenoses: implications for dobutamine stress testing.

BACKGROUND: Although dobutamine stress is used with both 99mTc sestamibi (sestamibi) myocardial perfusion imaging and echocardiography for detecting coronary artery stenoses, the impact of stenosis severity on test end points (myocardial sestamibi uptake and systolic thickening, respectively) has not been clearly defined. METHODS AND RESULTS: In 15 open-chest dogs, dobutamine (2.5 to 30 microg x kg(-1) x min(-1)) was infused after placement of an LAD stenosis that reduced (n=8) or abolished (n=7) flow reserve. In dogs with reduced flow reserve, the stenotic-to-normal sestamibi activity ratio (0.86+/-0.03) significantly underestimated the approximately 2-to-1 dobutamine-induced flow disparity at the time of sestamibi injection (flow ratio, 0.53+/-0.04; P<.001). Stenotic-zone thickening increased at low but not at higher doses of dobutamine (2.9+/-0.4 versus 4.2+/-0.4 mm in normal zone at peak dobutamine; P=.055) but did not fall below baseline (2.7+/-0.3 mm). Similarly, in dogs with absent flow reserve, the sestamibi activity ratio (0.78+/-0.02) underestimated the approximately 2.5-to-1 dobutamine-induced flow disparity (flow ratio, 0.41+/-0.05; P<.001), and failure to increase systolic thickening was observed in the stenotic zone (2.7+/-0.4 versus 4.6+/-0.3 mm in the normal zone at peak stress, P<.01). In both groups of dogs, myocardial sestamibi uptake and image defect magnitudes were less than expected for the dobutamine-induced hyperemia, suggesting that dobutamine adversely affects myocardial sestamibi binding. Finally, a significant reduction in stenotic-zone thickening was seen during postdobutamine recovery, consistent with myocardial stunning. CONCLUSIONS: In the presence of stenoses that reduced or abolished regional flow reserve, (1) myocardial sestamibi uptake significantly underestimated the dobutamine-induced flow heterogeneity, (2) a "failure to increase systolic thickening" rather than a reduction in thickening was observed during dobutamine stress, and (3) myocardial stunning was observed during postdobutamine recovery.