Comparison of technetium-99m sestamibi and thallium-201 retention characteristics in canine myocardium.

OBJECTIVES. The aim of this study was to compare the myocardial retention of technetium-99m (Tc-99m) sestamibi and thallium-201 over a wide range of blood flow at different time points after tracer injection. BACKGROUND. Technetium-99m sestamibi has been proposed as a new perfusion tracer with better physical characteristics than those of thallium-201 for scintigraphic imaging. However, no studies have simultaneously compared the ability of both tracers to assess myocardial blood flow during pharmacologic vasodilation. METHODS. The myocardial retention of Tc-99m sestamibi and thallium-201 were compared over a wide range of blood flow induced by regional coronary occlusion and dipyridamole infusion in an open chest dog model. Myocardial retention of both tracers was determined by in vitro tissue counting at 2, 5, and 20 min after tracer injection and was correlated with microsphere-determined blood flow. RESULTS: Thallium-201 demonstrated greater absolute tissue retention than did Tc-99m sestamibi. At 2 min after tracer injection, there was an almost linear relation between the retention of both tracers and myocardial blood flow over a wide flow range. However, this relation was not maintained over time. At 20 min after injection, the retention of both tracers underestimated myocardial blood flow at higher flow rates. At 2, 5 and 20 min after injection, increments of relative tracer retention between the different levels of flow were always greater for thallium-201 than for Tc-99m sestamibi. CONCLUSIONS. Thallium-201 displays more suitable physiologic characteristics as a flow tracer and may allow better differentiation of myocardial regions with different levels of coronary flow reserve. For both tracers, early cardiac imaging may minimize underestimation of blood flow at higher flow rates.     

Experimental studies of the physiologic properties of technetium-99m agents: myocardial transport of perfusion imaging agents

The physiologic properties of new technetium-99m-labeled myocardial imaging agents (Tc-99m sestamibi, an isonitrile; and Tc-99m teboroxime, a boronic acid adduct of technetium dioxime) are discussed and compared to thallium-201 (Tl-201). Studies with isolated hearts, subcellular fractions and cell cultures indicate that Tc-99m sestamibi, Tc-99m teboroxime and Tl-201 do not share common transport or sequestration mechanisms. Although peak Tc-99m sestamibi myocardial extraction over time is about half that of Tl-201 at equivalent coronary blood flows, the amount of Tc-99m sestamibi that remains in the heart is similar to that of Tl-201 because of its higher retention efficiency. The high retention efficiency for Tc-99m sestamibi also results in minimal redistribution. In contrast, Tc-99m teboroxime myocardial extraction is higher than that of Tl-201, but its retention is less efficient, resulting in relatively rapid washout characteristics which may quickly result in tracer redistribution. During reperfusion after a no-flow period, Tc-99m sestamibi extraction and retention increase, but for Tc-99m teboroxime and Tl-201 these values tend to decrease. All tracers show adequate transport characteristics for perfusion imaging, and differences in transport and retention should lead to the development of new clinical protocols.     

Comparison of 99mTc-teboroxime with thallium for myocardial imaging in the presence of a coronary artery stenosis

BACKGROUND. This study tested the hypotheses in the setting of a coronary artery stenosis that 1) planar 99mTc-teboroxime myocardial scans are capable of providing a good estimate of relative coronary flow reserve, and 2) delayed washout of the tracer from the myocardium is a marker of reduced myocardial blood flow and, in certain cases, myocardial ischemia. METHODS AND RESULTS. Experiments were conducted in eight closed-chest domestic swine prepared with an artificial stenosis that reduced diameter of the left anterior descending coronary artery by 80%. Measurements of hemodynamics, regional myocardial blood flow, oxygen, and lactate metabolism were made 1) at baseline, 2) after 5 minutes of intravenous infusion of adenosine and neosynephrine ("stress"), and 3) at recovery 2 hours after discontinuing the adenosine/neosynephrine infusion. Simultaneous intravenous injection of teboroxime (approximately 9 mCi) and thallium (approximately 3.5 mCi) was made at peak stress, and serial planar teboroxime imaging began 1-2 minutes later. Scans were made in dynamic mode for 30 seconds each for 7 minutes after which a stress thallium scan (7 minutes acquisition) was obtained. A redistribution thallium scan was made 2 hours later after which a repeat teboroxime injection followed by serial imaging for 7 minutes was performed. The animal was then killed, and the heart removed for determination of microsphere activity. Under baseline conditions, transmural myocardial blood flow (ml/min/g) distal to the stenosis (1.06 +/- 0.17) was reduced (p less than 0.01) compared with the normally perfused circumflex zone (1.50 +/- 0.31). In response to intravenous infusion of adenosine/neosynephrine, flow increased (p less than 0.01) compared with baseline in both distal (2.00 +/- 0.84) and circumflex (4.67 +/- 1.55) zones. However, the distal : circumflex flow declined (0.45 +/- 0.17) compared with baseline (0.73 +/- 0.17; p less than 0.01). Two hours later flow had returned to baseline levels in both zones, and lactate production during stress (-41.7 +/- 37.5 mumol/min/100 g) had reverted to consumption (13.6 +/- 7.7; p less than 0.05). Analysis of stress teboroxime scans demonstrated 1) an increase (p less than 0.01) in the ischemic : normal zone (IZ:NZ) count between 30-second (0.50 +/- 0.14) and 7-minute scans (0.61 +/- 0.11); 2) a good correlation between the 30-second scan IZ:NZ count and the stress distal : circumflex flow (0.45 +/- 0.17; r = 0.74; p less than 0.05; slope = 0.90; intercept = 0); and 3) a close correlation between the IZ:NZ count of the 7-minute scan (0.61 +/- 0.11) and the recovery distal : circumflex flow (0.69 +/- 0.21; r = 0.89; p less than 0.01). The IZ:NZ count also increased (p less than 0.01) between 30-second (0.65 +/- 0.15) and 7-minute (0.72 +/- 0.14) scans following rest injection of teboroxime. As anticipated, serial thallium scans demonstrated evidence of redistribution between stress (IZ:NZ count = 0.62 +/- 0.08) and recovery (IZ:NZ count = 0.75 +/- 0.06; p less than 0.01) time points. The stress thallium scan IZ:NZ, however, was greater than that of the 30-second teboroxime scan as well as that of the stress distal : circumflex flow. CONCLUSIONS. Accordingly, the data indicate that 1) myocardial imaging with 99mTc-teboroxime is valuable in the noninvasive assessment of relative coronary flow reserve and that 2) delayed washout of the tracer from the myocardium reflects reduced myocardial blood flow and, under conditions comparable to those of the present study, may be a marker of myocardial ischemia.     

Tomographic myocardial perfusion imaging with technetium-99m teboroxime during adenosine-induced coronary hyperemia: correlation with thallium-201 imaging.

Single-photon emission computed tomographic imaging with technetium-99m teboroxime during exercise has been found to be feasible and the results correlate with those obtained with thallium-201. This study examined the feasibility of this technique and compared tomographic imaging with technetium-99m teboroxime during adenosine-induced coronary hyperemia with thallium-201 imaging. With the patient positioned on the imaging table, adenosine was infused at a rate of 140 micrograms/kg per min for 6 min. At 4 min, 20 to 25 mCi (740 to 925 MBq) of technetium-99m teboroxime was injected intravenously and imaging was started as soon as the infusion was completed with use of a 180 degrees anterior arc and 32 stops at 10 s/stop (total imaging time 7.8 min). Rest images were obtained 60 to 90 min later with use of a similar dose of technetium-99m teboroxime. Exercise tomographic thallium images were obtained within 2 weeks of the teboroxime studies. In the 20 patients studied, the teboroxime images were normal in 2 (50%) of 4 normal subjects and abnormal in 15 (94%) of 16 patients with coronary artery disease; 4 of the 15 had a fixed defect and 11 a reversible defect. There was agreement between teboroxime and thallium studies in 16 patients (80%), in 319 (80%) of 400 segments and in 50 (83%) of 60 vascular segments (p less than 0.05). In two normal subjects, an apparent fixed defect involving the inferior wall was seen on the teboroxime but not the thallium images and was thought to be due to an attenuation artifact secondary to extracardiac activity in the left lobe of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)     

Technetium-99m isonitrile myocardial uptake at rest. I. Relation to severity of coronary artery stenosis

To determine the potential of planar technetium-99m methoxybutyl isonitrile myocardial imaging as a method of detecting totally occluded or severely stenosed coronary arteries, the regional distribution of technetium-99m isonitrile at rest was compared with the coronary anatomy in 38 patients with prior myocardial infarction who underwent coronary arteriography. Left ventricular technetium-99m isonitrile tracer uptake at rest was assessed in the three major coronary vascular territories. When qualitative rest technetium-99m isonitrile uptake was markedly reduced or absent (grade 0), there was a 91% probability of finding a totally occluded or severely stenosed coronary artery. When qualitative tracer uptake was reduced (grade 1) or normal (grade 2), it excluded all territories supplied by a totally occluded vessel with poor collateral flow. Quantitative technetium-99m isonitrile uptake (mean +/- 1 standard deviation) in territories supplied by an occluded coronary artery with poor collateral flow (42 +/- 21%) was lower than in territories supplied by a vessel with less than 50% stenosis (87 +/- 10%) and 50 to 99% stenosis (74 +/- 19%) (p less than 0.001). Furthermore, technetium-99m isonitrile uptake in areas supplied by an occluded coronary artery with good collateral flow (61 +/- 23%) was lower than in areas supplied by a vessel with less than 50% stenosis (87 +/- 10%) (p less than 0.001). Because rest technetium-99m isonitrile imaging detects coronary occlusion with poor collateral flow, this method may be useful in assessing patients with acute myocardial infarction.     

Noninvasive quantification of regional blood flow in the human heart using N-13 ammonia and dynamic positron emission tomographic imaging

Evaluation of regional myocardial blood flow by conventional scintigraphic techniques is limited to the qualitative assessment of regional tracer distribution. Dynamic imaging with positron emission tomography allows the quantitative delineation of myocardial tracer kinetics and, hence, the measurement of physiologic processes such as myocardial blood flow. To test this hypothesis, positron emission tomographic imaging in combination with N-13 ammonia was performed at rest and after pharmacologically induced vasodilation in seven healthy volunteers. Myocardial and blood time-activity curves derived from regions of interest over the heart and ventricular chamber were fitted using a three compartment model for N-13 ammonia, yielding rate constants for tracer uptake and retention. Myocardial blood flow (K1) averaged 88 +/- 17 ml/min per 100 g at rest and increased to 417 +/- 112 ml/min per 100 g after dipyridamole infusion (0.56 mg/kg) and handgrip exercise. The coronary reserve averaged 4.8 +/- 1.3 and was not significantly different in the septal, anterior and lateral walls of the left ventricle. Blood flow values showed only a minor dependence on the correction for blood metabolites of N-13 ammonia. These data demonstrate that quantification of regional myocardial blood flow is feasible by dynamic positron emission tomographic imaging. The observed coronary flow reserve after dipyridamole is in close agreement with the results obtained by invasive techniques, indicating accurate flow estimates over a wide range. Thus, positron emission tomography may provide accurate and noninvasive definition of the functional significance of coronary artery disease and may allow the improved selection of patients for revascularization.     

Clinical experience with technetium-99m teboroxime, a neutral, lipophilic myocardial perfusion imaging agent

Technetium-99m (Tc-99m) teboroxime is a new technetium-based myocardial perfusion imaging agent (investigational code = SQ30217 [Cardiotec, Squibb Diagnostics]). A member of a class of neutral, lipophilic, technetium-containing complexes known as boronic acid adducts of technetium dioxime (BATO) complexes, this agent is chemically very different from the cationic tracer thallium-201 (Tl-201) and from the cationic technetium complex Tc-99m sestamibi (Cardiolite, Du Pont Imaging Agents). Tc-99m teboroxime has high myocardial extraction, rapid blood clearance, little lung uptake and rapid myocardial washout. A biexponential pattern of myocardial washout is demonstrated in animals and in man. Effective half-lives of the 2 washout components in man are 5.2 minutes and 3.8 hours and represent approximately 66 and 33% of the myocardial activity, respectively. The first half-life for the myocardium is approximately 11 minutes. As the agent washes out of the heart, hepatic uptake occurs, peaking at about 5 minutes after injection. The liver is the major organ of excretion and receives, along with the large bowel, the largest radiation dose. Rapid imaging protocols using standard cameras have achieved good myocardial counts from 3 planar views acquired over a 4- to 5-minute period or for single photon emission computed tomography (SPECT) images acquired over a 10-minute period. An entire stress/rest procedure can be completed in 1 hour. Analysis of data from 155 patients from 4 centers using planar or SPECT imaging showed a sensitivity and specificity for blinded readings of 82 and 91%, respectively, when compared against overall clinical impression.(ABSTRACT TRUNCATED AT 250 WORDS)     

Positron emission tomographic measurements of absolute regional myocardial blood flow permits identification of nonviable myocardium in patients with chronic myocardial infarction

Objectives. This study tested the hypothesis that nonviable myocardium can be identified by quantitative measurements of regional myocardial blood flow obtained using positron emission tomography in conjunction with a mathematical model of nitrogen-13 (N-13) ammonia tracer kinetics.Background. Under steady state basal conditions there is a minimal level of blood flow required to sustain myocardial viability. Therefore, the hypothesis predicts that regions with flow below a certain threshold are likely to be composed primarily of scar.Methods. Studies were conducted in 26 patients with chronic myocardial infarction. Positron emission tomographic measurements of basal regional myocardial blood flow (N-13 ammonia) and fluorine-18 (F-18) fluorodeoxyglucose uptake were made and correlated with information about coronary anatomy and regional wall motion to assess myocardial viability.Results. In patients with chronic myocardial infarction, normal zone blood flow (0.81 ± 0.32 ml/min per g [mean ± SD]) was greater (p < 0.02) than that of border zones (0.59 ± 0.29 ml/min per g), which in turn exceeded (p < 0.001) that of infarct zone flow (0.27 ± 0.17 ml/min per g). Good correlation was noted between relative F-18 fluorodeoxyglucose uptake and relative regional myocardial blood flow in all zones (r = 0.63, p < 0.001). Mismatch between blood flow and F-18 fluorodeoxyglucose uptake, with a single exception, was not observed in any segment with blood flow < 0.25 ml/min per g. All dyskinetic segments (n = 5) also had blood flow < 0.25 ml/min per g. In contrast, 43 of 45 myocardial segments (23 patients) with normal contraction or only mild hypokinesia had flow ≥ 0.39 ml/min per g (average flow 0.78 ± 0.35 ml/min per g).Conclusions. In patients with chronic myocardial infarction, myocardial viability is unlikely when basal regional myocardial blood flow is < 0.25 ml/min per g. Average basal flow in segments with normal or nearly normal wall motion is 0.78 ± 0.35 ml/min per g. Thus, positron emission tomographic measurement of regional myocardial blood flow is helpful in identifying nonviable myocardium in these patients.     

Comparison of maximal myocardial blood flow during adenosine infusion with that of intravenous dipyridamole in normal men.

OBJECTIVE. This study compared quantitatively the efficacy of intravenous adenosine and dipyridamole for pharmacologic induction of myocardial hyperemia. BACKGROUND. Pharmacologic vasodilation is used increasingly for induction of myocardial hyperemia in conjunction with radionuclide imaging of myocardial blood flow. Although both intravenous dipyridamole and adenosine have been used, the magnitude of hyperemia induced by these agents and the hyperemia to baseline blood flow ratios have not been quantified and compared. METHODS. Twenty normal volunteers were studied with dynamic positron emission tomography (PET) and intravenous nitrogen-13 ammonia. Myocardial blood flow was quantified with a two-compartment tracer kinetic model. RESULTS. Myocardial blood flow at rest averaged 1.1 +/- 0.2 ml/min per g and increased significantly to 4.4 +/- 0.9 ml/min per g during adenosine and 4.3 +/- 1.3 ml/min per g after dipyridamole administration. Hyperemia to baseline flow ratios averaged 4.3 +/- 1.6 for adenosine and 4.0 +/- 1.3 for dipyridamole. The average flow ratios and the maximal flows achieved were similar for both agents, but there was considerable variation in the individual response to these agents, as indicated by the range of hyperemia to baseline flow ratios (from 2.0 to 8.4 for adenosine and from 1.5 to 5.8 for dipyridamole). In addition, the hyperemic responses to dipyridamole and to adenosine differed by greater than 1 ml/min per g in nine subjects. CONCLUSIONS. Despite these inter- and intraindividual differences, we conclude that both agents are equally effective in producing myocardial hyperemia.     

Noninvasive quantitation of myocardial blood flow in human subjects with oxygen-15-labeled water and positron emission tomography

Noninvasive measurement of myocardial blood flow in absolute terms (i.e., milliliters per gram per min) has been difficult to accomplish despite the intrinsically quantitative power of positron emission tomography because of the nonphysiologic nature of tracers that have been employed conventionally as well as the limited spatial resolution of currently available instruments. It was previously demonstrated that myocardial blood flow in animals can be quantitated accurately with the diffusible tracer oxygen-15-labeled water (H2(15)O) when the arterial input function and myocardial radiotracer concentration were measured directly. To extend the approach for completely noninvasive measurement of blood flow, a parameter estimation procedure was developed whereby effects of limited tomographic spatial resolution and cardiac motion were compensated for within the operational flow model. In validation studies in 18 dogs, myocardial blood flow measured with positron emission tomography after intravenously administered H2(15)O correlated closely with flow measured with concomitantly administered radiolabeled microspheres over the range of 0.29 to 5.04 ml/g per min (r = 0.95). Although regional ischemia was clearly identifiable tomographically, absolute flow could not be determined accurately in ischemic regions in four dogs because of poor count statistics related to wall thinning. Subsequently, myocardial blood flow was measured in 11 normal human subjects. Flow was homogeneous throughout the myocardium, averaged 0.90 +/- 0.22 ml/g per min at rest and increased to 3.55 +/- 1.15 ml/g per min after intravenous administration of dipyridamole. Therefore, positron emission tomography with H2 15O and the approach developed permits noninvasive measurement of myocardial blood flow in absolute terms in humans and should facilitate objective assessment of interventions designed to enhance nutritive perfusion.     

Measurement of myocardial blood flow by ultrafast computed tomography

Myocardial blood flow was analyzed by radioisotope-labeled microspheres and ultrafast computed tomography (CT) in 16 closed-chest, anesthetized dogs. The first set of 10 dogs had CT and microsphere measurements before and after chromonar-induced increases in myocardial blood flow. A second set of six dogs had flows measured at control and during temporary reductions in regional flow produced by balloon cuff occlusion of the left anterior descending coronary artery. All dogs had four-slice, 20-instance CT scans after injection of a medium bolus (0.35 ml/kg) of contrast medium into a femoral vein simultaneous with injection of microspheres into the left atrium. CT myocardial flow was calculated as the change in myocardial CT numbers divided by the area from a blood pool time-density curve. A wide range of myocardial blood flows was produced as determined by microspheres (0 to 6.7 ml/min/g). Global flow of the first set of dogs was shown to have excellent correlation (r = .95, n = 17) for a limited range (.4 less than X less than 1.4 ml/min/g) of flows. Regional flows of these measurements demonstrated less correlation (r = .63, n = 110) but extended the range of flow to 1.7 ml/min/g. At higher flows (greater than 2.5 ml/min/g) the correlation for global and regional flows was not significantly different than zero. Regional ischemic flow correlation extended the linear range of flow to 0 ml/min/g (r = .62, n = 17). These results show that CT can measure myocardial blood flow over a limited but clinically relevant range of flows defined as slightly above normal to ischemic. These results indicate that another preparation of CT flow measurement must be sought for quantification of myocardial perfusion values significantly above normal.     

Effect of ischemia and postischemic dysfunction on myocardial uptake of technetium-99m-labeled methoxyisobutyl isonitrile and thallium-201

The myocardial uptake of a new technetium-99m-labeled myocardial perfusion agent, methoxyisobutyl isonitrile (Tc-99m MIBI), and thallium-201 was correlated with microsphere flow in an open chest canine model of low coronary flow and postischemic dysfunction. Eighteen dogs were given an injection of thallium-201 (0.5 mCi) and Tc-99m MIBI (5 mCi) either after 40 min of partial left anterior descending artery occlusion (Group I, 10 dogs) or during reperfusion after 15 min of left anterior descending artery occlusion (Group II, 8 dogs). Regional dysfunction was documented during injection in both groups by quantitative two-dimensional echocardiography. Regional blood flow was assessed by radiolabeled microspheres. The heart was excised 15 min after radionuclide injection and the left ventricle divided into 96 segments for gamma well counting. Among Group I dogs, central ischemic thallium-201 and Tc-99m MIBI activity (expressed as a percent of the activity in the corresponding nonischemic zone) was comparable, respectively, for endocardial (54 +/- 17% and 52 +/- 17%), mid-wall (71 +/- 20% and 69 +/- 17%) and epicardial (89 +/- 13% and 94 +/- 9%) segments and increased proportionally with flow. There was a good linear correlation among these endocardial segments between flow and both thallium-201 (r = 0.78) and Tc-99m MIBI (r = 0.85) activity. Among Group II dogs, central ischemic endocardial flow (59 +/- 14%) was comparable to thallium-201 (70 +/- 18%) and Tc-99m MIBI (74 +/- 12%) activity. Similarly, relative endocardial flow in the intermediate ischemic region (71 +/- 11%) was comparable to thallium-201 (77 +/- 11%) and Tc-99m MIBI (81 +/- 10%) activity. Thus, myocardial uptake of Tc-99m MIBI and thallium-201 is comparable under conditions of low coronary flow and postischemic dysfunction and closely parallels flow alterations.     

The scoring system for early technetium-99m pyrophosphate scintigraphy as a method of evaluation of limiting the myocardial infarct size by thrombolysis.

The usefulness of a scoring system with early technetium-99m pyrophosphate scintigraphy as a method for evaluating the efficacy of myocardial preservation after thrombolysis was studied. The mean time from the onset of acute myocardial infarction to injection of the tracer was 5.6 +/- 1.5 h (range 2.8 to 11.9 h). All 36 patients underwent successful recanalization. Patients with strongly positive technetium-99m pyrophosphate uptake in anterior acute myocardial infarction had a significantly lower regional ejection fraction and a significantly larger thallium-201 defect score than those with 2+ positive results in chronic stage. Similarly, in inferior acute myocardial infarction, the thallium-201 defect score was significantly larger in patients with strongly positive uptake than in those with 2+ and negative uptake scores. In conclusion, strongly positive results in early technetium-99m pyrophosphate scintigraphy within 12h after the onset of acute myocardial infarction may indicate failure in limiting the infarct size by coronary thrombolysis.     

Myocardial transport of hexakis(2-methoxyisobutylisonitrile) and thallium before and after coronary reperfusion

Effects of no-flow ischemia (NFI) and reperfusion (RPF) on myocardial extraction and retention of technetium-99m hexakis(2-methoxyisobutylisonitrile) (sestamibi) and thallium-201 were investigated in 12 isolated, blood-perfused rabbit hearts with isotope dilution studies at constant coronary perfusion. After a control injection of tracers, NFI was induced for 30-60 minutes. After coronary reflow, repeat tracer injections were given at early RPF (5-15 minutes of RPF) and late RPF (40-60 minutes of RPF). After NFI-RPF, maximal fractional extraction and capillary permeability-surface area product increased for sestamibi (from +39% to 69%) and decreased for thallium (from -14% to -68%). Net extraction was 33% lower for sestamibi than for thallium at control, 13% lower at early RPF, and 90% higher than thallium at late RPF. Interstitial-myocyte exchange estimates were always higher for sestamibi than for thallium and increased for both with NFI-RPF (sestamibi, from 57.4 to 122.4 ml/min/g; thallium, from 3.1 to 22.3 ml/min/g). Intramyocyte volumes of distribution were higher for sestamibi than for thallium (greater than 200% at control, 800-1,000% with RPF), and NFI-RPF had opposite effects on the two tracers (late RPF vs. control: +28% for sestamibi, -50% for thallium). Our results suggest that sestamibi and thallium have different transport or sequestering mechanisms and that NFI-RPF had opposite effects on myocardial capillary-tissue exchange and tissue retention of sestamibi and thallium. Therefore, myocardial perfusion might be overestimated with sestamibi and underestimated with thallium during early RPF.     

Comparison of technetium-99m teboroxime tomography with automated quantitative coronary arteriography and thallium-201 tomographic imaging

Technetium-99m (Tc-99m) teboroxime is a new perfusion tracer that is highly extracted and rapidly cleared by the myocardium. To determine the feasibility of Tc-99m teboroxime imaging in the diagnosis of patients with suspected coronary artery disease, 30 patients underwent single photon emission computed tomography imaging with Tc-99m teboroxime (25.2 +/- 1 mCi) at peak exercise and again 60 min later at rest. All patients underwent either a thallium stress test (n = 26) or automated quantitative coronary arteriography (n = 25), or both, without intervening revascularization or infarction. Images were reviewed by two investigators who had no knowledge of clinical data. Coronary lesions with greater than or equal to 50% diameter narrowing by quantitative coronary arteriography were considered significant. Both thallium and Tc-99m teboroxime detected disease in all patients with two or three vessel disease. One vessel disease was detected with Tc-99m teboroxime in 9 of 10 patients and with thallium in 8 of 10 (p = NS). In patients without angiographically significant disease. Tc-99m teboroxime demonstrated normal perfusion in six of eight patients and thallium in three of five (p = NS). Overall, when presence or absence of disease detected by Tc-99m teboroxime or thallium was compared with quantitative coronary arteriography, there was no difference between Tc-99m teboroxime and thallium. These results suggest that Tc-99m teboroxime is comparable to thallium as an imaging agent. The rapid biologic half-life, 5.3 min, allows studies to be completed in 60 to 90 min.     

Clinical experience with technetium-99m teboroxime scintigraphy in patients referred for myocardial perfusion evaluation

A series of 30 patients (25 males, 5 females, age=28–73 years) with a clinical indication of thallium-201 stress/4 hours redistribution scintigraphy has been studied using stress/rest (n=7) or rest/stress (n=23) protocols with technetium-99 m teboroxime (CARDIOTEC, Squibb Diagnostics) in order to assess the clinical usefulness of this new molecule and to compare it to thallium. In all cases coronary artery disease was known or highly suspected, with a history of myocardial infarction in 18 cases (subacute n=6, remote n=12) and/or previous by-pass surgery or PTC A in 5 cases. Medical treatment was not discontinued at the time of stress testing. Coronary angiography was available for 27 patients.Exercise tests for both tracers were carried out on an ergometric bicycle during the same day and the levels of exercise achieved for the thallium studies were very similar to those achieved for teboroxime.Imaging was performed in three planar projections and sudies were evaluated using a model with 4 territories: septal and anterior assumed to correspond to the LAD artery, lateral and latero-posterior (=LCX), inferior and posterior (=RCA) and apex. Classification of results was: normal, ischemic, infarcted and infarcted with ischemia.With reference to the thallium-201 results, agreement was found in 86% (37/43) of normal regions and in 82% (63/77) of abnormal regions. Relative to documented coronary artery lesions (27 patients) sensitivity and specificity of thallium and teboroxime for exact correspondence between arteries and territories were, respectively: thallium, se=71%, sp=64%, teboroxime, se=67%, sp=75%.These results indicate the ability of Cardiotec to evaluate myocardial perfusion with an important time saving since the complete study durations (stress and rest) were: thallium=4h 34 min –22 min and teboroxime=1 h 57 min –41 min.     

Usefulness of rapid low-dose/high-dose 1-day 99mTc-sestamibi ECG-gated myocardial perfusion single-photon emission computed tomography.

BACKGROUND: The clinical usefulness of a rapid rest low-dose/stress high-dose (dose ratio =1:5) (99m)Tc-sestamibi myocardial perfusion single-photon emission computed tomography (SPECT) protocol for the detection of coronary artery disease was evaluated. METHODS AND RESULTS: In 89 patients, rest images were obtained immediately after the injection of (99m)Tc-sestamibi (256.1+/-28.4 MBq) followed by drinking water (400 ml). Exercise or vasodilator stress test was performed immediately after the completion of rest imaging with the injection of (99m)Tc-sestamibi (1312.3 +/-167.6 MBq). Prior to the post-stress imaging, patients were asked again to drink water (400 ml) in order to eliminate subdiaphragmatic tracer activity. The myocardial count ratio (stress/rest) of (99m)Tc-sestamibi was calculated. Image quality was scored using a 4-point scale system (4= excellent, 3= good, 2= poor, 1= unacceptable). Coronary angiography was performed in 56 patients within 1 month of the SPECT scan. All patients successfully performed the protocol and total examination time was 108+/-7 min. The myocardial count ratio of (99m)Tc-sestamibi was always greater than 6. The image quality was satisfactory both at rest (3.4+/-0.9) and after stress (3.9+/-0.2). The sensitivity and specificity to detect coronary artery stenosis >50% was 84% and 97%, respectively. CONCLUSIONS: This rapid one-day (99m)Tc-sestamibi protocol provides adequate image quality and diagnostic accuracy for detecting coronary artery disease.     

Measurement of infarct size using single photon emission computed tomography and technetium-99m pyrophosphate: a description of the method and comparison with patient prognosis

The application of dual tracer transaxial emission computed tomography of the heart was studied with use of technetium-99m pyrophosphate and technetium-99m-labeled red blood cells for measuring infarct size in 20 patients with acute myocardial infarction and 10 without infarction. Imaging was performed with a standard gamma camera and with a multidetector transaxial emission computed tomographic body scanner 3 hours after injection of technetium-99m pyrophosphate. Immediately after the scanning procedure, technetium-99m pertechnetate was injected to label red blood cells, and the scanning protocol was repeated. Technetium-99m pyrophosphate was detected in the anterior wall with involvement of the interventricular septum or lateral wall in patients with electrocardiographic criteria for anterior infarction, whereas uptake was detected in the diaphragmatic left ventricular wall with involvement of the posterior, posteroseptal or posterolateral left ventricle or of the right ventricle in patients with electrocardiographic criteria for inferior or posterior infarction. Infarct size measured from transaxial images ranged from 14.0 to 117.0 g in weight. There was a direct relation between infarct size and patient prognosis in that, of the 13 patients with infarct greater than 40 g, 11 (85 percent) had complications, whereas only 2 (29 percent) of 7 patients with an infarct less than 40 g had complications during a follow-up period averaging 17.8 months (p less than 0.05).     

Regional myocardial blood flow during acute myocardial infarction in the conscious dog.

Regional myocardial blood flow was studied in the conscious dog at periods of 5 minutes to 4 days after occlusion of a major branch of the left coronary artery. Dogs were instrumented with aortic electromagnetic flow probes, occlusive cuffs on either the anterior descending or circumflex branch of the left coronary artery, and a left atrial Silastic catheter for injection of microspheres (15 +/- 5 mum) labeled with either 85Sr, 141Ce, or 51Cr. Microspheres were injected into 25 fully conscious dogs during three of the following time periods: control preocclusion and 0.1, 2, 6, 24, or 96 hours postocclusion. In the conscious dog, before occlusion, the endocardial half of the left ventricular myocardium received 28% more blood flow than the epicardial half. After sudden occlusion of a coronary artery branch, there was a marked reduction in blood flow as well as an alteration in distribution of blood flow within the ischemic tissue; blood flow was most severly reduced in the subendocardial center of the ischemic region, less so in the epicardial ischemic region, and least reduced in the marginal region of the infarct. Blood flow was increased to the nonischemic tissue. There was no change in this pattern of reduced blood flow by 6 hours postocclusion, but by 24 hours, flow was moderately increased to all areas except the central subendocardial core, and was further increased at 96 hours. Blood flow to the endocardial half of the left ventricular myocardium averaged 63 ml/100 g per min during the control period, was reduced to 12-18 ml/100 g per min at 0.1-6 hours in the ischemic region, increased to 29 ml/100 g per min at 24 hours, and to 48 ml/100 g per min by 96 hours. These findings indicate that there is a reversal of the flow ratio within ischemic myocardium with relative under-perfusion of the endocardial half of the wall, which is not corrected by 4 days. There is a modest increase of collateral blood flow to ischemic tissue by 24 hours and this increase is considerably augmented by 96 hours, apparently as a result of the growth and enlargement of collateral vessels.     

Comparison of the myocardial uptake of a technetium-labeled isonitrile analogue and thallium

The myocardial transmicrovascular transport of thallium-201 (201Tl) and technetium-99m hexakis(2-methoxyisobutylisonitrile) (MIBI) were compared during variable blood flow levels in nine blood-perfused, isolated rabbit hearts. Seventeen injections of radiolabeled albumin and EDTA as well as 201Tl and MIBI were performed by indicator-dilution techniques. When coronary flow was varied from 0.52 to 3.19 ml/g/min, myocardial extraction for MIBI averaged 0.38 +/- 0.09 (SD) whereas 201Tl myocardial extraction averaged 0.73 +/- 0.10 (p less than 0.001). Net extraction, which was calculated using end points of 1.8-4.9 minutes, averaged 0.41 +/- 0.15 for MIBI and was less than the 201Tl net extraction of 0.57 +/- 0.13 (p less than 0.001). The mean capillary permeability-surface area product for MIBI (0.44 +/- 0.13 ml/g/min) was one third of 201Tl (1.30 +/- 0.45 ml/g/min; p less than 0.001). However, parenchymal cell permeability-surface area product for MIBI (47.58 +/- 25.85 ml/g/min) was much higher than 201Tl (6.52 +/- 6.51 ml/g/min; p less than 0.0001), and apparent cellular volume of distribution for MIBI (15.15 +/- 3.31 ml/g) was also higher than 201Tl (10.19 +/- 4.00 ml/g; p less than 0.01). These data suggest that capillary permeability for 201Tl is greater than MIBI, but the reverse is true at the parenchymal cell wall. In addition, a new blood-perfused preparation is used for indicator-dilution techniques, and previously developed modeling analyses are also extended to these experiments.