A comparison of the overall first-pass kinetics of thallium-201 and technetium-99m MIBI in normoxic and low-flow ischaemic myocardium

The specific impact of ischaemia on the myocardial kinetics of thallium-201 and technetium-99m 2-methoxy-2-isobutylisonitrile (MIBI) remains a matter of debate. Using an isolated heart model perfused with red blood cell-enhanced perfusate, we compared the overall first-pass kinetics of ²⁰¹Tl and MIBI under haemodynamically stable conditions of low-flow ischaemia (>50% reduction in normal coronary flow and a ₀ mmHg fall in systolic contraction pressure, n=10) and normoxia (n=11). For both ²⁰¹Tl and MIBI, we found that under ischaemic conditions (as compared with normoxia) there was a higher initial net extraction fraction (²⁰¹Tl: 0.78ǂ.03 vs 0.72ǂ.06, P=0.006; MIBI: 0.49ǂ.10 vs 0.39ǂ.11, P=0.03), a lower clearance rate in the 30 min following extraction (% decrease in cardiac uptake: ²⁰¹Tl: 30ᆠ vs 47ᆢ, P=0.02; MIBI: 5LJ vs 13ᆟ, P=0.02) and a higher retention fraction at 30 min (²⁰¹Tl: 0.54ǂ.10 vs 0.39ǂ.12, P=0.004; MIBI: 0.46ǂ.08 vs 0.33ǂ.12, P=0.01). Multivariate analyses, however, revealed that all myocardial kinetic parameters of both tracers were dependent only on coronary flow rates, without any additional significant impact of the presence of ischaemia or states of contractility or oxidative metabolism. We conclude that the myocardial fractional retention of both ²⁰¹Tl and MIBI is strongly correlated with the decrease in coronary flow during ischaemia. This inverse relationship with coronary flow derives from both the flow-dependent increase in the initial myocardial extraction and the decrease in the subsequent myocardial washout of the tracers.     

Low-flow ischaemia has no deleterious effect on the steady-state kinetics of 201Tl and 99mTc sestamibi within myocardial tissue

OBJECTIVES: This study aimed to specifically analyse the impact of low-flow ischaemia on the ability of myocytes to trap and accumulate Tl and sestamibi (MIBI) within myocardial tissue. METHODS: In order to reach steady-state conditions for the interstitial/cellular concentration ratios (Ci/Cc) of the tracers and thereby simulate the conditions of cell cultures studies, Tl and MIBI were injected continuously during an 80 min period within the coronary circulation of isolated hearts submitted to normoxia (n=7) or low-flow ischaemia (n=7; >50% reduction in coronary flow). Ci was determined by using interstitial microdialysis and Cc was determined from Ci and myocardial retention values of the tracers. RESULTS: At the end of the experiments, under steady-state conditions, Ci/Cc was equivalent between low-flow ischaemia and normoxia for both Tl (ischaemia, 0.60 +/- 0.25% vs normoxia, 0.63 +/-0.34%; NS) and MIBI (ischaemia, 1.00 +/- 0.68% vs normoxia, 0.76 +/- 0.32%, NS), whereas tissue concentrations of ATP were more than 4-fold lower in ischaemia than in normoxia (5.1 +/- 3.5 nmol.g vs 22.5 +/- 4.8 nmol.g; P< 0.001). CONCLUSIONS: In contrast to the published results concerning the effects of anoxia on cell cultures, low-flow ischaemia within myocardial tissue has no deleterious effects on the ability of the cells to accumulate Tl and MIBI under steady-state conditions. This gives definitive evidence of the negligible impact of cellular metabolic disorders in the decrease in Tl or MIBI uptake, which is documented by stress-SPECT within low-flow ischaemic myocardium.     

(201)Tl and (99m)Tc-MIBI retention in an isolated heart model of low-flow ischemia and stunning: evidence of negligible impact of myocyte metabolism on tracer kinetics.

It is not known whether cellular metabolic disorders play a role in the decreased tracer uptake that is documented by conventional SPECT during low-flow ischemia or stunning. This study sought to determine the impact of low-flow ischemia and stunning on the kinetics of (201)Tl and MIBI across the plasma membrane of myocytes. METHODS: The global myocardial retention (Rf) of (201)Tl and MIBI was determined in isolated working hearts from rabbits, perfused with red blood cell-enhanced solution. Experiments were performed in normoxia, with physiological values of coronary flow (N; n = 16); in low-flow ischemia, with a >50% reduction of coronary flow and a > or =20-mm Hg fall in systolic left ventricle pressure (L; n = 15); and in stunning, with 15 min of acute ischemia followed by reperfusion (S; n = 15). Concentration ratios across the plasma membrane of myocytes were also determined for both tracers and expressed as Ci/Cc, where Ci is interstitial activity determined with microdialysis, and Cc is activity from cellular space determined from Rf and Ci values. RESULTS: There was a slight increase in average values of Ci/Cc in ischemia, but not in stunning, for (201)Tl (L, 0.011 +/- 0.006 vs. N, 0.006 +/- 0.004 [P < 0.05]; S, 0.007 +/- 0.004 vs. N [not significant]) and for MIBI (L, 0.011 +/- 0.008 vs. N, 0.005 +/- 0.004 [P < 0.05]; S, 0.005 +/- 0.003 vs. N [not significant]). Moreover, ischemia and stunning had no deleterious effects on the average values of global myocardial retention for (201)Tl (L, 0.63 +/- 0.09 vs. N, 0.50 +/- 0.14 [P < 0.05]; S, 0.59 +/- 0.10 vs. N [P < 0.05]) or for MIBI (L, 0.45 +/- 0.10 vs. N, 0.31 +/- 0.09 [P < 0.05]; S, 0.41 +/- 0.12 vs. N [P < 0.05]). In fact, these values were significantly enhanced in the 2 situations. CONCLUSION: The kinetics of (201)Tl and MIBI across the plasma membrane of myocytes were affected only poorly by low-flow ischemia and not at all by stunning, without any deleterious effects on myocardial retention of both tracers. During low-flow ischemia or stunning, therefore, the information provided by (201)Tl or MIBI SPECT is expected to depend on myocardial perfusion but not on cellular metabolic disorders.     

The effect of flow on technetium-99m-teboroxime (SQ30217) and thallium-201 extraction and retention in rabbit heart

In order to evaluate the accuracy of blood flow measurement, the single-pass extraction, retention/wash-out and relative net uptake of 99mTc-teboroxime (SQ30217) and 201Tl were evaluated and compared in 20 isolated blood-perfused rabbit hearts at coronary flow rates ranging from 0.49 to 2.85 ml/g wet wt min-1. The average peak extraction of 201Tl (+/- s.d.) (0.67 +/- 0.11) marginally exceeded that of SQ30217 (0.62 +/- 0.12) (p = 0.06). Flow significantly affected the maximum net extraction of 201Tl and the 40-min net extractions of both 201Tl and SQ30217. Unexpectedly, the rate of 201Tl myocardial washout was significantly faster (p less than 0.05) than SQ30217 washout at all flow rates evaluated. Increasing coronary blood flow rate was associated with a more rapid clearance of both tracers from the myocardium (p less than 0.05 for both comparisons). The slope of the linear correlations between relative net SQ30217 uptake versus flow and relative net 201Tl uptake versus flow were found to be similar for up to 10 min after isotope injection. These data were interpreted to indicate that: 1. Thallium-201 might be slightly better extracted than SQ30217. 2. SQ30217 is cleared more slowly from the myocardium. 3. Thallium-201 and SQ30217 appear to be comparable tracers of myocardial perfusion for up to 10 min after injection under the single-pass conditions currently employed. 4. Additional studies are needed to clarify myocardial SQ30217 kinetics.     

Arbutamine stress perfusion imaging in dogs with critical coronary artery stenoses: (99m)Tc-sestamibi versus (201)Tl.

Having previously shown that dobutamine reduces (99m)Tc-methoxyisobutylisonitrile (sestamibi [MIBI]) uptake in normal myocardium by elevating intracellular calcium, we hypothesized that arbutamine, which has less inotropic effect than dobutamine, might cause less reduction in MIBI uptake, thereby improving defect contrast. In this study using a canine model, we compared the effects of arbutamine stress on myocardial blood flow, myocardial MIBI uptake, and systolic thickening in the presence of a coronary artery stenosis. METHODS: Arbutamine was infused (0.5-250 ng/kg/min) in 8 open-chest dogs with critical coronary stenoses that abolished flow reserve. At the time of peak arbutamine effect, MIBI (296 MBq), (201)Tl (27.75 MBq), and microspheres were coinjected. The dogs were killed 5 min later, and myocardial tracer activities and flow were quantified by well counting. Ex vivo imaging of heart slices was also performed. RESULTS: Arbutamine increased mean heart rate, peak positive left ventricular pressure and its first time-derivative, and normal-zone myocardial thickening. Stenotic zone flow and thickening did not increase during arbutamine infusion. MIBI uptake versus flow was significantly lower than (201)Tl uptake at the same flow values. By imaging, defect magnitude (stenotic/normal) was greater for (201)Tl than MIBI (0.57 vs. 0.77; P < 0.001) [corrected]. CONCLUSION: In the presence of coronary stenoses that abolished regional flow reserve, myocardial uptake of MIBI, compared with (201)Tl, significantly underestimated the arbutamine-induced flow heterogeneity. The attenuation of MIBI uptake and diminished defect contrast during arbutamine stress were comparable with those previously reported for dobutamine stress.     

Myocardial scintigraphy with iodine-123 phenylpentadecanoic acid and thallium-201 in patients with coronary artery disease: a comparative dual-isotope study.

To characterise the clinical usefulness of serial myocardial scintigraphy with iodine-123 phenylpentadecanoic acid (IPPA) in comparison with thallium-201, dual-isotope investigations were performed in 41 patients with angiographically documented coronary artery disease. Both tracers were administered simultaneously during symptom-limited ergometry. Planar scintigrams were acquired immediately after stress, and delayed imaging was performed after 1 h for IPPA and 4 h for 201Tl. Scintigrams were evaluated both qualitatively and quantitatively using a newly developed algorithm for automated image superposition. Initial myocardial uptake of both tracers was closely correlated (r = 0.75, p < 0.001). Both tracers also revealed a similar sensitivity for the identification of individual coronary artery stenoses > or = 75% (IP-PA: 70.0%, 201Tl: 66.3%, P = NS) with identical specificity (69.8%). The number of persistent defects, however, was significantly higher with IPPA (P = 0.021), suggesting that visual analysis of serial IPPA scintigrams may overestimate the presence of myocardial scar tissue. On the other hand, previous Q wave myocardial infarction was associated with a decreased regional IPPA clearance (29% +/- 11% vs 44% +/- 11% in normal myocardium, P < 0.05). The data indicate that serial myocardial scintigraphy with IPPA is essentially as sensitive as scintigraphy with 201Tl for the detection of stress-induced perfusion abnormalities. Quantitative analysis of myocardial IPPA kinetics, however, is required for the evaluation of tissue viability.     

Kinetic analysis of 18F-fluorodihydrorotenone as a deposited myocardial flow tracer: comparison to 201Tl.

The goals of this investigation were to assess the accuracy of (18)F-fluorodihydrorotenone ((18)F-FDHR) as a new deposited myocardial flow tracer and to compare the results to those for (201)Tl. METHODS: The kinetics of these flow tracers in 22 isolated, erythrocyte- and albumin-perfused rabbit hearts were evaluated over a flow range encountered in patients. The 2 flow tracers plus a vascular reference tracer ((131)I-albumin) were introduced as a bolus through a port just above the aortic cannula. Myocardial extraction, retention, washout, and uptake parameters were computed from the venous outflow curves with the multiple-indicator dilution technique and spectral analysis. RESULTS: The mean +/- SD initial extraction fractions for (18)F-FDHR (0.85 +/- 0.07) and (201)Tl (0.87 +/- 0.05) were not significantly different, although the initial extraction fraction for (18)F-FDHR declined with flow (P < 0.0001), whereas the initial extraction fraction for (201)Tl did not. The washout of (201)Tl was faster (P < 0.001) and more affected by flow (P < 0.05) than was the washout of (18)F-FDHR. Except for the initial extraction fraction, (18)F-FDHR retention was higher (P < 0.001) and less affected by flow (P < 0.05) than was (201)Tl retention. Reflecting its superior retention, the net uptake of (18)F-FDHR was better correlated with flow than was that of (201)Tl at both 1 and 15 min after tracer introduction (P < 0.0001 for both comparisons). CONCLUSION: The superior correlation of (18)F-FDHR uptake with flow indicates that it is a better flow tracer than (201)Tl in the isolated rabbit heart. Compared with the other currently available positron-emitting flow tracers ((82)Rb, (13)N-ammonia, and (15)O-water), (18)F-FDHR has the potential of providing excellent image resolution without the need for an on-site cyclotron.     

Monocationic radiotracer kinetics and myocardial infarct size: a perfused rat heart study

OBJECTIVE: To compare the myocardial kinetics of three (99m)technetium-labeled monocationic tracers [methoxy-isobutylisonitrile (MIBI), tetrofosmin, and Q12] in a model of ischemia-reperfusion (IR) to determine their abilities to assess myocardial viability. METHODS: Isolated perfused rat hearts (n = 30) were studied in control and IR groups for each tracer. IR hearts were treated with 120 min global no-flow followed by 5 min reflow, then 60 min tracer uptake/clearance. Tracer kinetics were monitored using a scintillation detector. RESULTS: This model produced significant myocardial injury, without significant differences in the percentage of injured myocardium by triphenyltetrazolium chloride (TTC) staining and creatine kinase (CK) assay. Transmission electron microscopy analysis also confirmed necrosis with abundant mitochondrial damage in the IR hearts. All three IR groups exhibited significantly less mean (+/-standard error of the mean) tracer retention than matched controls (MIBI 73.4 +/- 4.9% vs. 96.9 +/- 1.76%, tetrofosmin 38.7 +/- 4.6% vs. 82.2 +/- 3.5%, and Q12 23.0 +/- 2.5% vs. 43.8 +/- 1.8%, respectively; P < 0.05). Tetrofosmin IR hearts exhibited 54 +/- 9% of control myocardial retention, which was significantly less than either MIBI (86 +/- 5%, P < 0.05) or Q12 (63 +/- 6%, P < 0.05); thus, tetrofosmin provided the best differentiation between nonviable and normal myocardium. Furthermore, tetrofosmin end activity (%id/g) in controls was significantly higher than Q12 (4.09 +/- 0.04 vs. 1.71 +/- 0.06, respectively, P < 0.05), and tetrofosmin end activity (%id/g) in IR hearts was significantly higher than Q12 (2.19 +/- 0.37 vs. 1.06 +/- 0.12, respectively, P < 0.05). The correlation between end activity and viable myocardium determined by TTC staining was r = 0.66 (P < 0.05) for MIBI, r = 0.94 (P < 0.05) for tetrofosmin, and r = 0.91 (P < 0.05) for Q12. The correlation between myocardial end activity and myocardial CK leak was r = -0.62 (P < 0.05) for MIBI, r = -0.87 (P < 0.05) for tetrofosmin, and r = -0.89 (P < 0.05) for Q12. CONCLUSIONS: Nonviable myocardium can be distinguished from normal myocardium by the retention kinetics of all three monocationic tracers studied. Tetrofosmin and Q12 end activities demonstrate the best correlation with infarct size. However, tetrofosmin kinetics may combine the greatest differentiation between nonviable and normal myocardium, while still retaining adequate activity for imaging.     

The kinetics of beta-methyl-substituted labelled fatty acids in ischaemic myocardium: an analysis in man and with a blood-perfused isolated heart model.

beta-Methyl-substituted free fatty acids (FFAs) have been developed for myocardial single-photon emission tomography (SPET) imaging, but little is known about their kinetics in ischaemic conditions. The aim of this study was to determine the changes in the myocardial kinetics of a beta-methyl-branched FFA, [123I]16-iodo-3-methyl-hexadecanoic acid (MIHA), under ischaemic conditions. The kinetics of MIHA were analysed: (a) using a blood-perfused isolated heart model subjected to moderate ischaemia (50% flow reduction) and (b) in patients who had an exercise thallium-201 SPET defect corresponding to either necrotic (n = 13) or chronically ischaemic and viable (n = 15) myocardium, and who underwent two consecutive SPET studies after MIHA injection. In animals, the myocardial early retention fraction of MIHA, but not its clearance rate, was dependent on coronary flow, the early retention fraction being higher in ischaemic than in normoxic conditions (0.24 +/- 0.10 vs 0.14 +/- 0.04, P = 0.004). In the patient SPET studies, the uptake of MIHA calculated in ischaemic and viable areas (G1: 74% +/- 9% of maximal left ventricular value) was different from that calculated in necrotic (G2: 59% +/- 7%, P < 0.001) or normal (G3: 88 +/- 6%, P < 0.001) areas. By contrast, MIHA-clearance calculated between the two consecutive SPET studies was not different in G1, G2 and G3. Unlike in the case of other FFAs, the myocardial clearance of MIHA is not decreased by ischaemia. However, the early retention of MIHA is increased in the case of a moderate reduction in coronary flow, a property which might help in the detection of viability in chronically ischaemic myocardium.     

Detection of stent restenosis in single vessel CAD: comparison of 201Tl and gated 99mTc-MIBI SPECT

BACKGROUND AND AIM: After successful percutaneous transluminal coronary angioplasty (PTCA), stent restenosis is observed in up to 40% of patients during the first year. The aim of this study was to determine the value of myocardial perfusion studies (MPSs) in the detection of stent restenosis in a symptomatic patient cohort. METHODS: A total of 80 patients without prior myocardial infarction (MI) and who underwent one-vessel PTCA with stent implantation were included to study. The diagnostic accuracy of two study protocols, Tl single photon emission computed tomography (SPECT) (38 patients) and rest-stress same day gated Tc sestamibi (MIBI) SPECT (42 patients), were compared. MPS data were visually evaluated by two experienced observers and stress induced perfusion defects with reversibility at rest was considered as restenosis. In gated MIBI data the wall motion (WM) and ejection fraction (EF) were also noted. The diagnostic value of a semiquantitative method based on 20 segment model and summed stress scores (SSSs) and summed difference scores (SDSs) were also tested. Results of MPSs were compared with control coronary angiography (CA) in all patients and agreement was defined as the kappa value (kappa). RESULTS: The average time between stent implantation and MPS was 8.9 +/- 2 months. Restenosis was detected in 58% of patients in CA. No significant differences were observed regarding age, gender, achieved exercise levels, vascular territorial distribution of lesions, imaging time interval after PTCA and degree of restenosis between Tl and gated MIBI groups. MPSs identified stent restenosis in 41 of 47 patients (sensitivity, 87%; specificity, 82%; accuracy, 85%; kappa=0.69). Four of six occluded stents that could not be detected in MPSs revealed intermediate degree stenosis (50-70%). Sensitivity, specificity and accuracy were not significantly different but better for gated MIBI group when compared to Tl (sensitivity, 90-83%; specificity, 85-80%; accuracy, 88-82%). Semiquantitative evaluation using SSS and SDS reached lower sensitivity than qualitative evaluation (MIBI, 90% vs 69%; Tl, 83% vs 72%) but higher specificity (MIBI, 85% vs 92%; Tl, 80% vs 100%) for both tracers and SSS were significantly correlated with occlusion degree (r=0.69). EF values calculated from the gated MIBI study were also inversely correlated with occlusion degree (r=0.55) and significantly different in patients with occluded stents (P<0.001). Agreement with CA for both tests were adequate (kappa=0.73, for MIBI; and kappa=0.63, for Tl). CONCLUSION: Semiquantitative evaluation of MPSs using SSS may enhance diagnostic specificity in the detection of stent restenosis. Both Tl and gated MIBI studies accurately detected stent restenosis. The gated MIBI method has advantages of WM analysis and evaluation of EF.     

Thallium gated SPECT: relation between immediate post-stress evolution of ejection fraction and severity of perfusion pattern

BACKGROUND AND AIMS: A significant decrease of left ventricular ejection fraction (LVEF) at stress has been reported with 99Tc(m) gated single-photon emission computed tomography (gSPECT) in severe myocardial stunning up to 1 h after exercise. This study was designed to show whether 201Tl gSPECT can measure LVEF evolution from rest to stress in routine examination and give additional information to perfusion interpretation since acquisition starts immediately after stress test. METHODS: Post-exercise and rest 201Tl gSPECT were performed in 187 patients with suspected coronary artery disease. Myocardial perfusion was quantified by 20-segment analysis. Patients were divided into four groups according to their summed perfusion score, reversibility rate and electrocardiographic findings, i.e. in order of severity: I = normal perfusion, II = fixed defect owing to a myocardial infarction, III = full reversible ischaemia, and IV = partial reversible ischaemia. LVEF was calculated by Germano's automatic algorithm. RESULTS: Normal subjects (n = 29) and infarcted patients (n = 34) showed a significant LVEF increase between rest and stress, +7 +/- 9% and +5 +/- 7% respectively. In full reversible ischaemic patients (n = 46), stress LVEF showed no increase (+1 +/- 8%) and this group was statistically different from both group I and group II. Furthermore, when ischaemia was partially reversible (n = 31), LVEF decreased significantly (-3 +/- 8%), particularly when exercise tests were abnormal (-4 +/- 8%). Group IV was statistically different from groups I and II. CONCLUSIONS: Good agreement exists between the severity of ischaemic perfusion pattern and LVEF degradation at stress, which is consistent with previously published data using 99Tc(m) gSPECT. Additionally, the use of 201Tl for immediate post-exercise imaging allows the observation of a physiological LVEF increase in normal and infarcted patients.     

A comparison of three radionuclide myocardial perfusion tracers in clinical practice: the ROBUST study

There are no large studies available to guide the selection of thallium (Tl), methoxyisobutylisonitrile (MIBI) or tetrofosmin (Tf) for myocardial perfusion imaging. Our objective was to compare the technical and clinical performance of the three in routine clinical practice. We randomised 2,560 patients to receive Tl, MIBI or Tf. A 1-day stress/rest protocol was used for MIBI and Tf. Tracer uptake was scored using a 17-segment model, quality and artefact scores were assigned, and ratios of heart (H), liver (L), subdiaphragmatic (S) and lung activity were measured. Mean quality scores (stress/rest) were Tl 2.13/2.16, MIBI 2.18/2.39, Tf 2.18/2.42 ( P=ns stress and <0.00001 rest). For attenuation artefact, Tl>MIBI=Tf ( P<0.05) and for low-count artefact Tl>MIBI>Tf ( P<0.001). For H/S, Tl>MIBI=Tf, for H/L Tl>MIBI=Tf, and for H/lung Tl相似文献   

Effects of grisorixin on the distribution of thallium-201 and on the oxidative metabolism in cultured myocardial cells

Previous experiments in the dog and guinea-pig have shown that grisorixin, a monocarboxylic ionophore, can significantly increase the coronary blood flow and the myocardial uptake of 201Tl, as well as have a stimulant effect on the heart. In this study, cultures of myocardial cells were used in order to isolate the cells from the vascular and extracardiac influences so that any ionophorous effect on 201Tl could be evidenced. The effects of grisorixin on the oxidative metabolism were simultaneously studied. The technique described by Harary was used to prepare the cultures. The activity of the 14CCO2 produced by oxidation of [14C]glucose and [14C]octanoate added to the medium of culture and the intra/extracellular ratio of 201Tl concentrations (Tl i/e) were measured. In the controls (n = 8), the Tl i/e was 40 +/- 10 while it was 17 +/- 6 (p less than 0.05) in the cells that received 201Tl and grisorixin at the same time (n = 4), and 19 +/- 5 (p less than 0.05) in the flasks where 201Tl was injected after grisorixin (n = 7). A significant decrease of the [14C]octanoate oxidation was found in the flasks treated with grisorixin (n = 4, -50 +/- 16%, p less than 0.01) while the [14C]glucose oxidation was not significantly lowered (n = 3; -11 +/- 12%). The conclusion is that grisorixin decreases both the intracellular concentration of 201Tl and the fatty-acids oxidation in cultured myocardial cells. The beneficial effects previously observed in vivo were probably the consequence of the strong coronary dilatation and of an indirect stimulation.     

Changes in first-pass interstitial kinetics of DTPA in myocardium submitted to low-flow ischemia

OBJECTIVES: This study aimed to determine the changes during ischemia in the myocardial first-pass kinetics of DTPA, an extracellular tracer that is currently used for assessing myocardial perfusion with magnetic resonance imaging (Magnevist). MATERIALS AND METHODS: Using an indicator-dilution technique, first-pass kinetics of DTPA were compared between normoxia (n=11) and low-flow ischemia (n=11) in isolated rabbit hearts perfused with red blood cell-enhanced perfusate. RESULTS: There was no difference between ischemia and normoxia in the interstitial extraction and clearance rates of DTPA. Interstitial distribution volume of DTPA was, however, lower in ischemia than in normoxia (in percent of myocardial volume: 15+/-11% vs 25+/-11%, P=0.02) as a result of a relationship with coronary flow (P<0.001). CONCLUSIONS: During low-flow myocardial ischemia, DTPA kinetics are unchanged, except for the interstitial distribution volume that is decreased, presumably because of the shrinkage of extracellular fluid. These kinetic properties are favorable for detecting myocardial ischemia at rest with magnetic resonance imaging.     

201Tl and 99mTc-MIBI gated SPECT in patients with large perfusion defects and left ventricular dysfunction: comparison with equilibrium radionuclide angiography.

Left ventricular ejection fraction (LVEF) is a major prognostic factor in coronary artery disease and may be computed by 99mTc-methoxyisobutyl isonitrile (MIBI) gated SPECT. However, 201Tl remains widely used for assessing myocardial perfusion and viability. Therefore, we evaluated the feasibility and accuracy of both 99mTc-MIBI and 201Tl gated SPECT in assessing LVEF in patients with myocardial infarction, large perfusion defects and left ventricular (LV) dysfunction. METHODS: Fifty consecutive patients (43 men, 7 women; mean age 61 +/- 17 y) with a history of myocardial infarction (anterior, 26; inferior, 18; lateral, 6) were studied. All patients underwent equilibnum radionuclide angiography (ERNA) and rest myocardial gated SPECT, either 1 h after the injection of 1110 MBq 99mTc-MIBI (n = 19, group 1) or 4 h after the injection of 185-203 MBq 201Tl (n = 31, group 2) using a 90 degrees dual-head camera. After filtered backprojection (Butterworth filter: order 5, cutoff 0.25 99mTc or 0.20 201Tl), LVEF was calculated from reconstructed gated SPECT with a previously validated semiautomatic commercially available software quantitative gated SPECT (QGS). Perfusion defects were expressed as a percentage of the whole myocardium planimetered by bull's-eye polar map of composite nongated SPECT. RESULTS: Gated SPECT image quality was considered suitable for LVEF measurement in all patients. Mean perfusion defects were 36% +/- 18% (group 1), 33% +/- 17% (group 2), 34% +/- 17% (group 1 + group 2). LVEF was underestimated using gated SPECT compared with ERNA (34% +/- 12% and 39% +/- 12%, respectively; P = 0.0001). Correlations were high (group 1, r= 0.88; group 2, r = 0.76; group 1 + group 2, r = 0.82), and Bland-Altman plots showed a fair agreement between gated SPECT and ERNA. The difference between the two methods did not vary as LVEF, perfusion defect size or seventy increased or when the mitral valve plane was involved in the defect. CONCLUSION: LVEF measurement is feasible using myocardial gated SPECT with the QGS method in patients with large perfusion defects and LV dysfunction. However, both 201Tl and 99mTc-MIBI gated SPECT similarly and significantly underestimated LVEF in patients with LV dysfunction and large perfusion defects.     

Dobutamine stress thallium-201 single-photon emission tomography versus echocardiography for evaluation of the extent and location of coronary artery disease late after myocardial infarction.

Dobutamine stress echocardiography and thallium-201 myocardial perfusion scintigraphy are clinically useful methods for the evaluation of coronary artery disease (CAD). However, the relative merits of these imaging modalities in the evaluation of the extent of CAD after myocardial infarction have not been well studied. The aim of this study was to compare the accuracy of dobutamine stress echocardiography and simultaneous 201Tl single-photon emission tomography (SPET) imaging for the diagnosis and localization of CAD late after acute myocardial infarction. Dobutamine (up to 40 micrograms kg-1 min-1)-atropine (up to 1 mg) stress echocardiography in conjunction with stress-reinjection 201Tl SPET was performed for the evaluation of myocardial ischaemia in 90 patients with previous myocardial infarction who underwent coronary angiography. Significant CAD was predicted on bases of myocardial ischemia (new or worsening wall motion abnormalities on echocardiography and reversible perfusion defects on 201Tl SPET). Significant CAD (> or = 50% luminal diameter stenosis) was detected in 73 (81%) patients. The sensitivity, specificity and accuracy of echocardiography in detecting remote ischaemia for the diagnosis of remote CAD (present in 53 patients) were, respectively, 79% (CI 70%-88%), 85% (CI 77%-93%) and 81% (CI 73%-90%), while the corresponding figures for 201Tl SPET were 75% (CI 66%-85%), 78% (CI 69%-87%) and 76% (CI 67%-86%) respectively (P = NS vs echocardiography). The sensitivity, specificity and accuracy of echocardiography in detecting peri-infarction ischaemia for the diagnosis of infarct-related artery stenosis (present in 70 patients) were, respectively, 77% (CI 68%-86%), 85% (CI 78%-92%) and 79% (CI 70%-87%) while the corresponding figures for 201Tl SPET were 73% (CI 64%-82%), 85% (CI 78%-92%) and 76% (CI 67%-84%) respectively (P = NS vs echocardiography). The agreement between the two methods for the diagnosis of peri-infarction and remote ischaemia was 70% (kappa = 0.37) and 80% (kappa = 0.59) respectively. It is concluded that dobutamine stress echocardiography and 201Tl SPET have comparable accuracy for the diagnosis of infarct related and remote CAD in patients with previous myocardial infarction. The agreement between the methods is higher for the diagnosis of remote CAD than for that of peri-infarction ischaemia.     

Effects of acute ischemia and reperfusion on the myocardial kinetics of technetium 99m-labeled tetrofosmin and thallium-201

Background  Effects of no-flow ischemia and reperfusion on myocardial extraction and retention of ^99mTc-labeled tetrofosmin and ²⁰¹Tl were investigated in seven isolated, blood-perfused rat hearts with isotope dilution studies at constant coronary perfusion. Methods and Results  After a control injection of tracers, no-flow ischemia was induced for 20 minutes. After coronary reflow, tracers were injected. Both maximal fractional extraction and capillary permeability-surface area product for tetrofosmin were significantly less than those for ²⁰¹Tl (maximal fractional extraction 0.30±0.01 and 0.70±0.09, respectively, p<0.001; capillary permeability-surface area product 0.66±0.14 and 2.29±0.61, respectively, p<0.001). After no-flow ischemia-reperfusion, both maximal fractional extraction and capillary permeability-surface area product decreased for both tetrofosmin and ²⁰¹Tl (decreases in maximal fractional extraction of 23% and 7%, respectively; decreases in capillary permeability-surface area product of 27% and 16%, respectively), although the difference reached statistical significance only for tetrofosmin. Net extraction at 5 minutes of both tracers decreased significantly after no-flow ischemia-reperfusion (tetrofosmin 20% decrease, p<0.01; ²⁰¹Tl 23% decrease, p<0.02). Early (0 to 5 minutes) washout of tetrofosmin did not change after no-flow ischemia-reperfusion, whereas the ²⁰¹Tl value increased significantly. Although late (5 to 19 minutes) washout of both tracers increased significantly after no-flow ischemia-reperfusion, the myocardial clearance rates for tetrofosmin were always significantly less than those noted for ²⁰¹Tl. Conclusions  The myocardial uptake of tetrofosmin is depressed (independent of blood flow) after severe ischemic injury, apparently resulting mainly from decreased transcapillary exchange. In contrast, the depressed uptake of ²⁰¹Tl is related more to an accelerated early washout from injured myocardium than to a fairly stable initial transcapillary exchange. Amersham/Medi-physics Healthcare (Arlington Heights, Illinois, Provided tetrofosmin used in these experiments.     

Serial change of iodine-123 metaiodobenzylguanidine (MIBG) myocardial concentration in patients with dilated cardiomyopathy.

Serial change of the metaiodobenzylguanidine iodine-123 (123I-MIBG) myocardial concentration was investigated in patients with dilated cardiomyopathy (DCM). Eight DCM patients and 6 control subjects were examined. After the injection of thallium-201 and 123I-MIBG, planar chest images were obtained simultaneously for both tracers in every 30-60 min over 5 h. Serial changes of myocardial uptake ratio (MUR) were compared for both tracers. In DCM, the initial MUR of 123I-MIBG did not differ significantly from that of the controls. The washout of 123I-MIBG from the myocardium, however, was significantly increased in DCM. In particular, the decrease in the early phase (15-45 min) was significantly larger in DCM than in the controls (21.2% +/- 7.5% vs. 5.3% +/- 4.0%, P less than 0.01), showing a significant negative correlation with the left ventricular ejection fraction (r = -0.72 P less than 0.05). For 201Tl, neither the initial MUR nor the washout rate different significantly between the two. Thus, an early rapid decrease of the 123I-MIBG myocardial concentration might characterize DCM and reflect the severity of this disease.     

Prediction of improvement in global left ventricular function in patients with chronic coronary artery disease and impaired left ventricular function: rest thallium-201 SPET versus low-dose dobutamine echocardiography

Accurate assessment of myocardial viability permits selection of patients who would benefit from myocardial revascularization. Currently, rest-redistribution thallium-201 scintigraphy and low-dose dobutamine echocardiography are among the most used techniques for the identification of viable myocardium. Thirty-one consecutive patients (all men, mean age 60 +/- 8 years) with chronic coronary artery disease and reduced left ventricular ejection fraction (31% +/- 7%) were studied. Rest 201Tl single-photon emission tomography (SPET), low-dose dobutamine echocardiography and radionuclide angiography were performed before revascularization. Radionuclide angiography and echocardiography were repeated after revascularization. An a/dyskinetic segment was considered viable on 201Tl SPET when tracer uptake was >65%, while improvement on low-dose dobutamine echocardiography was considered a marker of viability. Increase in global ejection fraction was considered significant at > or = 5%. In identifying viable segments, rest 201Tl SPET showed higher sensitivity than low-dose dobutamine echocardiography (72% vs 53%, P<0.05), while specificity was not significantly different (86% vs 88%). In 17 patients, global ejection fraction increased > or = 5% (group 1) while in 14 it did not (group 2). A higher number of a/dyskinetic segments were viable on 201Tl SPET in group 1 than in group 2 (2.6 +/- 1.9 vs 0.6 +/- 1.2, P < 0.005), while no significant differences were observed on low-dose dobutamine echocardiography (1.7 +/- 1.6 vs 1.1 +/- 1.6). A significant correlation was found between the number of a/dyskinetic segments viable on 201Tl SPET and post-revascularization changes in ejection fraction (r = 0.52, P < 0.05), but such a correlation was not observed for low-dose dobutamine echocardiography. Using as the cut-off the presence of at least one viable a/dyskinetic segment, rest 201Tl SPET had a higher sensitivity (82% vs 53%, P = 0.07) and showed a trend towards higher accuracy and specificity (77% vs 58%, and 71% vs 64%, respectively) as compared with low-dose dobutamine echocardiography. In conclusion, these findings suggest that when severely reduced global function is present, rest 201Tl SPET evaluation of viability is more accurate than low-dose dobutamine echocardiography for the identification of patients who will benefit most from revascularization.     

The effect of nitroglycerin on myocardial blood flow in various segments characterized by rest-redistribution thallium SPECT.

The use of nitrates is reported to be effective in viability detection in scintigraphic perfusion imaging. The purpose of the study was to evaluate the effect of nitroglycerin (NTG) on myocardial blood flow (MBF) and coronary vascular resistance (CVR) in various segments characterized by rest-redistribution (201)Tl SPECT. METHODS: Twenty-three patients with coronary artery disease underwent rest-redistribution (201)Tl SPECT and (15)O-labeled water PET at rest and after NTG spray (0.3 mg). In addition, 11 healthy volunteers were also studied using PET. RESULTS: NTG did not change global MBF in the volunteers or in the patients. In segments with normal (201)Tl uptake and in those with a severe irreversible (201)Tl defect, NTG significantly reduced MBF without changing CVR. NTG reduced CVR in segments with a reversible (201)Tl defect (141 +/- 50 to 114 +/- 29 mm Hg/[mL/min/g], P = 0.004) and in those with a mild-to-moderate irreversible (201)Tl defect (165 +/- 64 to 149 +/- 60 mm Hg/[mL/min/g], P = 0.003), while maintaining MBF. CONCLUSION: NTG preferentially reduces CVR in the viable myocardium with ischemia. After NTG, tracer uptake in the ischemic myocardium will be relatively increased compared with that in the nonviable and nonischemic myocardium, leading to improvements in viability detection.