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Purpose: This study aimed to clarify the relationship between severity of conduction delay in the left ventricle and myocardial uptake of (99m)Tc-tetrofosmin (TF) in dilated cardiomyopathy (DCM) patients with left bundle branch block (LBBB)., Methods and Results: Thirty-two DCM patients with LBBB underwent electrocardiography and (99m)Tc-TF myocardial single-photon emission computed tomography (SPECT). SPECT images were acquired at 30 min (early images) and 3 h (late images) after injection. We calculated the total defect score (TDS) using a 20-segment model with a 5-point scoring system. The TDS in early and late images was defined as the summed early score (SES) and summed late score (SLS), respectively. On early images, 29 of 32 patients (91%) had decreased tracer uptake in the septum. All patients showed a decreased tracer uptake in the septum on late images. A significant correlation was observed between TDS (both SES and SLS) and QRS duration, with SLS showing an excellent correlation (SES: r = 0.554, P < 0.001; SLS: r = 0.779, P < 0.0001)., Conclusions: These findings suggest that in DCM patients with LBBB, hypoperfusion and myocardial damage in the septum might occur in accordance with an increase in the QRS duration.

Background: In technetium (Tc)-99m myocardial perfusion imaging (MPI), intestinal activity often interferes with the assessment of myocardial perfusion of the inferior wall. We examined whether a small amount of soda water prevents intestinal activity and improves image quality of the inferior wall in Tc-99m tetrofosmin MPI., Methods and Results: Ninety-five patients referred for 1-day rest/stress Tc-99m tetrofosmin MPI were assigned to one of two groups automatically, according to the date when they underwent MPI: the soda water group (n = 63) ingested 100 mL soda water just before image acquisition after adenosine stress, and the control group (n = 32) underwent no intervention. The frequency of intestinal activity was assessed visually on planar images. The inferior myocardial wall and the abdominal activity adjacent to the myocardium were assessed quantitatively on three different planar images during stress, and the mean inferior wall-to-abdomen (I/A) count ratio was calculated. The frequency of intestinal activity was 69.8% in the soda water group, and 90.6% in the control group (P = .038). The I/A count ratio was significantly higher in the soda water group than in the control group (1.98 +/- 0.51 vs 1.50 +/- 0.35, respectively, P < .0001, +/- SD)., Conclusions: The intake of 100 mL of soda water improves intestinal activity and improves the image quality of the inferior wall.

Background: Technetium 99m N-DBODC5 is a new myocardial perfusion tracer shown to exhibit high heart uptake and rapid liver clearance in normal rats. The objectives of this canine study were (1) to compare the organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 with Tc-99m sestamibi over a period of 3 hours in a more clinically relevant large animal species and (2) to compare the myocardial uptake of Tc-99m N-DBODC5 with thallium 201 when co-injected during vasodilator stress in dogs with coronary stenoses., Methods and Results: At peak adenosine-induced hyperemia, 10 dogs with critical left anterior descending artery stenoses received either Tc-99m N-DBODC5 (n = 6) or Tc-99m sestamibi (n = 4) and microspheres, followed by serial imaging and blood sampling over a period of 3 hours. Another 14 dogs with either critical (n = 7) or mild (n = 7) left anterior descending artery stenoses underwent simultaneous injection of Tc-99m N-DBODC5, Tl-201, and microspheres during peak vasodilator stress. Like sestamibi, Tc-99m N-DBODC5 showed good myocardial uptake with slow washout and minimal redistribution over a period of 3 hours (P = not significant); however, Tc-99m N-DBODC5 cleared more rapidly from the liver (heart-lung ratio at 30 minutes, 0.92+/-0.11 versus 0.51 +/- 0.05; P < .05). When injected during hyperemic flow, the myocardial extraction plateau for Tc-99m N-DBODC5 was lower than that for Tl-201 and was intermediate between Tc-99m sestamibi and Tc-99m tetrofosmin., Conclusions: Excellent organ biodistribution and myocardial uptake and clearance kinetic properties, combined with rapid liver clearance and a favorable flow-extraction relationship, make Tc-99m N-DBODC5 a very promising new myocardial perfusion imaging agent.

Background: Flattening of the interventricular septum (D-shaped left ventricle) detected during echocardiographic examination is correlated with significant right ventricular (RV) overload. There are no reports of this finding with cardiac gated single photon emission computed tomography (SPECT) imaging. We report an observational study correlating this finding with the presence of RV overload., Methods and Results: Retrospectively, we compared 8 cases with flattening of the interventricular septum on cardiac gated SPECT imaging for which echocardiographic correlations and clinical data were available regarding the presence of RV overload. All patients but 1 had pulmonary hypertension ranging from 42 to 52 mm Hg measured by echocardiographic Doppler studies. All patients but 1 had reasons for RV overload (chronic obstructive pulmonary disease in 3, history of atrial septal defect in 3, pulmonary embolism in 1, and obstructive sleep apnea in 1). Septal flattening present on gated SPECT images was seen in 50% of the cases by echocardiography. Other signs of RV overload (RV enlargement, RV hypertrophy) were observed by echocardiography in 5 patients and by the gated SPECT in 7 patients., Conclusion: The presence of interventricular septal flattening on gated SPECT studies correlates with RV overload and should be routinely assessed during interpretation of gated SPECT studies.

Background: The aim of this study was to investigate the effect of a standardized meal on intestinal activity in technetium 99m tetrofosmin myocardial perfusion scintigraphy., Methods and Results: The study population consisted of 60 patients (42 men and 18 women; mean age, 56 +/- 8 years) referred for myocardial perfusion imaging. All patients underwent same-day exercise-rest Tc-99m tetrofosmin single photon emission computed tomography (SPECT) imaging. All patients were given 200 mL of milk 15 minutes after the injection for the exercise SPECT study and just after the injection for the first rest SPECT study. None of the patients ate or drank between the exercise and the first rest SPECT studies. After the first rest SPECT study, 30 patients (meal group) were given a standardized meal of solid food and liquid to increase the volume of the stomach, and a second rest SPECT image was obtained 30 minutes after the end of the first rest SPECT study. In 30 patients (control group) a second rest SPECT image was obtained 30 minutes after the end of the first rest SPECT study, but this group did not eat or drink in this interval. The effect of the meal on intestinal activity was evaluated both visually and quantitatively. Frequency of intestinal activity was assessed visually on SPECT images. Inferior myocardial wall and abdominal activity adjacent to the myocardium was quantitatively assessed on 3 different planar projections in the rest studies, and the mean inferior wall-to-abdomen count ratio was calculated. In the meal group, inferior wall-to-abdomen count ratios in the first and second rest studies were 1.48 +/- 0.3 and 2.09 +/- 0.4, respectively (P <.0001), and in the control group, 1.41 +/- 0.2 and 1.40 +/- 0.2 (P >.05), respectively. The frequency of intestinal activity was 63% (n = 19) in the first rest SPECT study and 10% (n = 3) in the second study in the meal group (P <.0001); it was 66% (n = 20) in the first rest SPECT study and 76% (n = 23) in the second study in the control group (P >.05)., Conclusions: Our results indicate that filling of the stomach with a meal of solid food and liquid before rest acquisition may provide a high target-to-nontarget ratio. This simple modification may reduce the frequency of intestinal activity of Tc-99m-labeled radiopharmaceuticals in myocardial perfusion imaging.

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.

Background: 99mTc-labeled tetrofosmin is a new myocardial imaging agent that gives stable heart uptake. However, little is known about the mechanism of uptake in heart tissue. The aim of this study was to assess the factors responsible for the uptake and retention of 99mTc-labeled tetrofosmin in isolated heart mitochondria., Methods and Results: Mitochondria were isolated from adult rat heart tissue with competent metabolic function (i.e., respiratory control ratio of 3 and adenosine diphosphate/oxygen ratio of 2) for succinate oxidation. Intramitochondrial volume measured by the distribution of 3H-water and 14C-sucrose was 1.16 +/- 0.23 microliters/mg protein (mean +/- SD). In the isolated mitochondria, uptake could be demonstrated within 30 seconds of addition of oxidative substrate, but adenosine triphosphate alone did not stimulate marked uptake. Uptake was proportional to the amount of mitochondrial protein over a range of 0.2 to 3 mg protein but independent of Tc-labeled tetrofosmin concentration over a range of 0.4 to 200 pmol/L (0.1 to 50 microCi/ml). The presence of Tc-labeled tetrofosmin had no effect on the oxidative capability of the mitochondria. Use of the mitochondrial uncoupler 2,4-dinitrophenol caused release of 92% of radioactivity. Addition of Ca2+ to the mitochondria to partially depolarize the membrane resulted in partial release of activity. Application of the Nernst equation to the uptake data gave rise to a value of -163 mV for the mitochondrial membrane potential., Conclusion: It was concluded that the accumulation of 99mTc-labeled tetrofosmin by the mitochondria is related to their ability to transduce metabolic energy into electronegative membrane potential.

Background: 99mTc-labeled tetrofosmin is a new myocardial imaging agent that gives stable heart uptake. However, little is known about the mechanism of uptake in heart tissue., Methods and Results: Uptake of 99mTc-labeled tetrofosmin has been examined in isolated adult rat ventricular myocytes. The time course of uptake, efflux rate, and the effect of metabolic and cation channel inhibitors have been assessed. The subcellular localization of radioactivity in ex vivo rat heart tissue was examined by differential centrifugation of ventricular homogenate. Uptake into rat myocytes was found to be rapid and plateaued at approximately 1.5 pmol/10(6) cells/nmol extracellular Tc-labeled tetrofosmin after 60 minutes of incubation. Uptake was temperature dependent but independent of extracellular Tc-labeled tetrofosmin concentration. Uptake at 30 minutes was inhibited by the metabolic inhibitors iodoacetic acid acid and 2,4-dinitrophenol protein but was not affected by cation channel inhibitors. Cells previously incubated with 99mTc-labeled tetrofosmin and then placed into fresh medium were found to have a slow efflux of activity; after 1 hour, 65% of activity was still cell associated. The localization of radioactivity in subcellular fractions indicated that the majority of activity was recovered with the cytosol. However, examination of the distribution of two mitochondrial enzymes indicated that this may have been artifactual. Use of carbonyl cyanide m-chlorophenyl-hydrazone or oligomycin to perturb mitochondrial membrane potential decreased or increased recovery in the mitochondrial fraction, respectively., Conclusions: 99mTc-labeled tetrofosmin uptake by myocytes is by a metabolism-dependent process that does not involve cation channel transport. The most likely mechanism for this is by potential driven diffusion of the lipophilic cation across the sarcolemmal and mitochondrial membranes.