(Circulation. 2000;101:2424.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
99mTc-N-NOET Myocardial Uptake Reflects Myocardial Blood Flow and Not Viability in Dogs With Reperfused Acute Myocardial Infarction
From the Experimental Cardiology Laboratory, Cardiovascular Division, Department of Medicine, University of Virginia Health Sciences Center, Charlottesville, Va, and Cis-bio international, Gif sur Yvette, France (R.P.).
Correspondence to David K. Glover, ME, Cardiovascular Division, Department of Medicine, Box 500, Medical Center, University of Virginia Health Sciences Center, Charlottesville, VA 22908. E-mail dglover{at}virginia.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—N-Ethoxy-N-ethyl-dithiocarbamato-nitrido-99mTc (99mTc-N-NOET) is a new neutral lipophilic 99mTc-labeled myocardial perfusion agent with a high first-pass extraction fraction and delayed redistribution kinetics after transient ischemia comparable to what is observed with 201Tl. 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. 201Tl and 99mTc-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 201Tl and 99mTc-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 201Tl 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 99mTc-N-NOET activity in the same segments was 0.84±0.08 and 0.64±0.03, respectively (P<0.01 versus 201Tl; 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 99mTc-N-NOET reflects reperfusion myocardial blood flow and not viability in a canine model of reperfused acute myocardial infarction. The clinical use of early 99mTc-N-NOET imaging to assess the success of coronary reperfusion in patients with acute myocardial infarction should be investigated.
Key Words: radioisotopes • myocardial infarction • thallium • technetium
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The aim of thrombolytic therapy in the acute phase of myocardial infarction is to achieve early reperfusion of the infarct-related artery achieving TIMI-3 flow. Despite advances in this field, failure to achieve successful reflow still occurs in 30% to 40% of cases.1 Rescue PTCA may be useful in subsets of patients who fail to reperfuse with thrombolytic therapy.2 Clinical and ECG criteria for assessing the success or failure of thrombolysis are suboptimal,3 and deciding whether a patient is a candidate for rescue PTCA is often difficult. Myocardial contrast echocardiography has been shown to be of interest for such indication, but an intravenous myocardial contrast agent has not yet been validated for clinical applicability.4
Radionuclide perfusion imaging theoretically should be an excellent approach for assessing the efficacy of reperfusion early after thrombolytic therapy, but the myocardial uptake of tracers in clinical use is dependent on myocardial metabolic status and cellular viability and therefore will underestimate reperfusion flow in this setting.5 6 7 8 9 Results from studies using 99mTc-teboroxime, a neutral, highly lipophilic agent, in this setting are conflicting.10 11 Furthermore, rapid myocardial clearance of 99mTc-teboroxime limits its clinical usefulness for acute single photon emission CT (SPECT) imaging.12 13 N-Ethoxy-N-ethyl-dithiocarbamato-nitrido-99mTc (99mTc-N-NOET) is a new neutral, lipophilic myocardial perfusion imaging agent that has an uptake pattern that correlates well with myocardial blood flow in a canine model of myocardial ischemia14 and undergoes significant rest-redistribution over time in experimental models of transient coronary occlusion and sustained low coronary flow.14 15 Furthermore, cellular uptake of 99mTc-N-NOET has recently been shown to be independent of metabolic poisons that damage cell membranes and the cellular ATP content in cultured newborn rat cardiomyocytes.16
The aim of this study was to determine whether 99mTc-N-NOET uptake after coronary reperfusion, preceded by 180 minutes of coronary occlusion, will be more reflective of reperfusion flow than of cellular viability, because cellular uptake of 99mTc-N-NOET is not energy-dependent and does not require intracellular uptake for myocardial sequestration.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Surgical Preparation
Thirteen fasted male adult mongrel dogs were anesthetized with sodium pentobarbital (30 mg/kg), intubated, and ventilated on a respirator (Harvard Apparatus) with 4 cm H2O of positive end-expiratory pressure. Arterial blood gases were closely monitored, and appropriate ventilation adjustments were performed to maintain pH, PO2, PCO2, and HCO3 within physiological ranges. Lead II of the ECG was continuously monitored during the experiments. The left femoral vein was cannulated with an 8F polyethylene catheter (Cordis) for fluid administration, additional anesthesia, and 99mTc-N-NOET and 201Tl injections. Both femoral arteries were cannulated with similar catheters for arterial blood samples for blood gas determinations and radiolabeled microsphere reference blood withdrawals. The left main carotid artery was cannulated with an 8F sheath for monitoring systemic arterial pressure. A Millar high-fidelity pressure-recording catheter was introduced through this sheath and advanced into the LV cavity for measurement of LV pressure and dP/dt.
The open-chest canine surgical preparation used in these experiments was described previously.17 Briefly, a left thoracotomy was performed at the level of the fifth intercostal space, and the heart was suspended in a pericardial cradle. A 1.5-cm section of the LAD was dissected free of the epicardium and loosely encircled with a snare occluder. LAD and LCx coronary blood flows were measured with ultrasonic flow probes (T206, Transonic Systems), and regional systolic thickening in the LAD zone was measured with an epicardially located Doppler crystal (Crystal Biotech). Throughout each experiment, heart rate, systemic arterial pressure, left atrial pressure, LV pressure, dP/dt, ultrasonic flows, and LAD systolic wall thickening were continuously recorded on a 16-channel strip-chart recorder (Astromed) and simultaneously digitized and stored on a 133-MHz Pentium-based personal computer. All experiments were performed with the approval of the University of Virginia Animal Research Committee and were in compliance with the position of the American Heart Association on the use of research animals.
Experimental Protocol
After instrumentation, steady-state hemodynamic
measurements were made for 30 minutes, and radiolabeled
microspheres were injected for determination of baseline
myocardial blood flow (Figure 1
). Next,
the LAD was totally occluded, and a second set of microspheres
was injected 165 minutes later for determination of occlusion
myocardial blood flow. After a total of 180 minutes of occlusion, the
LAD was completely reperfused for an additional 180 minutes. After
either 60 (group 1, n=9) or 175 (group 2, n=4) minutes of reflow,
201Tl (18.5 MBq; 0.5 mCi) and
99mTc-N-NOET (296 MBq; 8 mCi) were coinjected
with a third set of microspheres. Group 1 dogs also had a
fourth set of microspheres injected at the end of the
experiment. Before the dogs were euthanized with an overdose of sodium
pentobarbital, the LAD was briefly reoccluded, and 20 mL of monastral
blue dye was rapidly injected into the left atrial catheter to
delineate the anatomic risk area.
|
Preparation and Quality Control of 99mTc-N-NOET
99mTc-N-NOET kits were obtained from
Cis-bio international. The preparation of this radiopharmaceutical has
been described in detail.16 Quality control was performed
with thin-layer chromatography with Silica gel plates
(J.T. Baker) and dichloromethane. Radiochemical purity was >90% in
each experiment.
In Vivo Image Acquisition and Defect Magnitude
Quantification
In the group 1 dogs, planar images were acquired in the left
lateral oblique projection with a standard gamma-camera (Technicare
420, Ohio Nuclear) equipped with an all-purpose, low-to-medium-energy
collimator at 5, 15, 30, 60, 90, and 120 minutes after tracer
injection. Background was subtracted from all images by use of a
previously validated interpolative algorithm18 without
thresholding or filtering. To quantify the
99mTc-N-NOET activity on images, regions of
interest (ROIs) were drawn on the defect area of the anteroseptal wall
supplied by the LAD and on the posterior wall supplied by the LCx. The
LAD/LCx defect count ratio was computed by dividing the average counts
in the ischemic ROI by the average counts in the
nonischemic ROI.
Microsphere-Derived Regional Myocardial Blood Flow and
201Tl and 99mTc-N-NOET Myocardial
Activities
The technique used in our laboratory to quantify myocardial
blood flow by radiolabeled microspheres was described
previously.19 After the dogs were euthanized, the LV was
divided into 4 slices 
1.5 cm thick, and each slice was divided into
6 transmural sections. Each of these transmural sections was then
subdivided into epicardial, midwall, and endocardial segments,
resulting in 72 LV segments. The myocardial segments were counted for
99mTc activity in a gamma-well counter (MINAXI
5550, Packard Instruments) within 24 hours. The myocardial segments
were recounted for 201Tl activity 3 days later
after 99mTc had decayed. Finally, a third count
was performed 3 weeks later for quantification of microsphere
activities when 201Tl activity was negligible.
The gamma-counter window settings were 113Sn, 340
to 440 keV; 103Ru, 450 to 550 keV;
95Nb, 640 to 840 keV; and
46Sc, 842 to 1300 keV. Tissue counts were
corrected for background, decay, and isotope spillover, and
regional myocardial blood flow was calculated by computer software
developed for this purpose (PCGERDA, Scientific Computing Solutions,
LLC).
Postmortem Determination of Risk Area and Infarct Size
The endocardial and epicardial surfaces of each heart slice and
the borders of the monastral blue dye–determined risk area were traced
on acetate sheets. The heart slices were then incubated for 10 minutes
at 37°C in a 2% solution of TTC to delineate infarct area. The
infarct area was then traced onto the previous acetate sheets. Risk
area (monastral blue dye–negative) and infarct areas (TTC-negative)
were determined with a digital planimeter program as previously
described.17
Data Analysis
Myocardial blood flows and tracer activities in each sample were
normalized to the average activity of 15 reference samples from the
posterior LV wall (5 transmural segmentsx3 layers) that exhibited
normal absolute myocardial blood flow during occlusion. Each
segment was then grouped according to the flow reduction observed
during the occlusion period. Segments with flow <0.3, 
0.3 and <0.5,
and 0.5 mL · min-1 ·
g-1 were classified as infarct, border, and
normal zones, respectively.
Statistical Analysis
Mean and SEM computations were performed with SYSTAT software
(SPSS, Inc). Comparisons within each group were made with either a
paired Student’s t test or repeated-measures ANOVA with
post hoc comparisons of changes determined, a priori, to be of
interest. In the group 2 dogs, linear regression analyses were
performed to assess the correlations between
201Tl and 99mTc-N-NOET
myocardial uptake with regional myocardial blood flow.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Hemodynamics
Hemodynamic data for the 13 dogs are summarized in Table 1
. There was no significant
difference in hemodynamic data between the 2 groups,
and therefore, the hemodynamic data were pooled. Heart
rate, left circumflex coronary artery (LCx) ultrasonic flow,
and maximum positive first derivative of LV pressure (dP/dt) did not
change throughout the experiments. Mean arterial pressure
remained constant during baseline, occlusion, and reperfusion but
decreased significantly at the end of the experiments. Mean left atrial
pressure increased significantly after occlusion and then remained
unchanged during occlusion and reperfusion. Ultrasonic left anterior
descending coronary artery (LAD) flow fell from 21±3 mL/min
during baseline to 0±0 mL/min after the occlusion was set
(P<0.001). Sixty minutes after reflow, at the time when
201Tl and 99mTc-N-NOET were
injected in 9 of the 13 dogs, LAD flow had returned to baseline (24±4
mL/min). However, as is frequently observed in experimental models of
coronary occlusion and reperfusion with severe infarction,
coronary flow gradually decreased in the reperfused LAD zone
over 3 hours.20 Regional systolic wall
thickening in the central region supplied by the LAD distal to the
occluder decreased from 21±2% during baseline to -6±1% after
occlusion (P<0.001) and remained constant throughout the
rest of the experiment during occlusion and after reperfusion.
|
Risk Area and Infarct Size
The risk area (monastral blue dye–negative area) was 29.9±1.8%
of the left ventricle (LV). By
triphenyltetrazolium chloride (TTC)
staining, 15.9±2.1% of the LV was infarcted. The infarct size was
43.8±4.4% of the risk area.
Microsphere Blood Flow
Table 2 summarizes the normalized
myocardial blood flow and 201Tl and
99mTc-N-NOET activities in normal, border-zone,
and infarcted samples from the 2 groups of dogs. In group 1 dogs,
regional myocardial blood flow ratios in the normal samples did not
change throughout the experiments. In group 2 dogs, there was a
statistically significant decrease in normal-zone flow between baseline
and occlusion. Nevertheless, flow in these segments during occlusion
(0.89 mL · min-1 ·
g-1) remained within the normal flow range of a
canine heart (0.8 to 1.2 mL · min-1
· g-1). In border-zone and infarcted samples
of both groups, there was a trend toward slightly higher myocardial
blood flow at baseline in group 2 versus 1; however, this difference
did not reach statistical significance. After the occlusion was set,
myocardial blood flow in the border and infarct zones decreased
significantly. There was no significant difference in the magnitude of
the flow reduction in the central infarct zone during the occlusion
between the 2 groups (0.18±0.04 versus 0.13±0.02 mL ·
min-1 ·
g-1). In group 1 dogs, there was complete
reperfusion at 60 minutes after reflow at the time when
201Tl and 99mTc-N-NOET were
injected, with no significant hyperemia. In contrast, group 2
dogs had significantly reduced flow at 3 hours after reflow when the
tracers were injected.
|
Comparison Between Myocardial 99mTc-N-NOET and
201Tl Activities
Group 1
As shown in Figure 2, when
99mTc-N-NOET was injected 1 hour after
reperfusion followed by 2 additional hours of reperfusion flow, the
final activity ratios in the border-zone and infarcted segments
(1.02±0.05 and 0.84±0.08) were significantly higher than those of
201Tl in the same segments (0.65±0.02 and
0.39±0.04). In addition, there was no significant difference between
the final 99mTc-N-NOET activity ratios and the
myocardial blood flow ratios at the time of injection (1.15±0.02 and
0.99±0.17) in these same segments. There was no significant difference
between 99mTc-N-NOET and
201Tl activities in the normal-zone segments.
|
0.5, and <0.3 mL ·
min-1 · g-1, respectively.
*P<0.05 vs reperfusion flow, 
P<0.001
vs 201Tl.
99mTc-N-NOET Activity by In Vivo Imaging
Figure 3 depicts mean
99mTc-N-NOET defect count ratios (LAD/LCx)
obtained from serial quantitative imaging in the group 1 dogs.
Substantial myocardial 99mTc-N-NOET uptake was
observed initially, with a defect count ratio of 0.72±0.06 at 5
minutes after injection. In addition, significant redistribution
resulted from differential myocardial clearance of
99mTc-N-NOET over the next 2 hours, with defect
count ratios of 0.71±0.08, 0.74±0.05, 0.77±0.04, 0.80±0.04, and
0.82±0.03 at 15, 30, 60, 90, and 120 minutes after injection,
respectively (ANOVA P<0.001).
|
Group 2
In the 4 group 2 dogs that received
99mTc-N-NOET and 201Tl
injections 3 hours after reperfusion, after which the dogs were
immediately killed, 99mTc-N-NOET activity was
highly correlated with reperfusion flow at the time of injection
(Figure 4). In contrast, there was poor
correlation between 201Tl activity and
reperfusion flow. Note that in all 4 examples shown in Figure 4, 99mTc-N-NOET activity tracked reperfusion
flow, whereas 201Tl activity in the same segments
fell below the line of identity; ie, 201Tl uptake
underestimated reperfusion flow, even in segments with complete
reperfusion (flow fraction 1.0). As expected,
99mTc-N-NOET and 201Tl
activities were comparable in no-reflow regions (flow fraction <0.5),
as well as in some segments with normal to high reperfusion flow that
presumably came from either the normal or viable border zones. Figure 5 shows a photograph of a TTC-stained
heart slice as well as 201Tl and
99mTc-N-NOET ex vivo images of the same heart
slice from a representative dog. As can be seen in this
figure, the large transmural infarct observed on the TTC photograph is
reflected by the large perfusion defect observed on the
201Tl image (defect count ratio=0.39). The defect
on the 99mTc-NOET image is less severe (defect
count ratio=0.58) and reflects the degree of flow restoration in this
region.
|
)
and 99mTc-N-NOET (•) activities vs flow at time of tracer
injection after reflow in 4 group 2 dogs. In all 4 dogs,
99mTc-N-NOET activity was highly correlated with
reperfusion flow, even though some segments were nonviable. In
contrast, 201Tl activity fell below identity line, and
there was poor correlation with flow in reperfused, nonviable segments.
Tracer activities were comparable in nonreperfused (no reflow) and in
reperfused, viable segments.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The main finding of this study is that 99mTc-N-NOET uptake in reperfused, acutely infarcted myocardium is significantly higher than that of simultaneously administered 201Tl and reflects myocardial blood flow restoration at the time of tracer injection, rather than myocardial viability. This finding is unique when 99mTc-N-NOET is compared with most of the other myocardial perfusion imaging agents administered in this setting.
Because 60% of 201Tl uptake is related to Na+/K+-ATPase activity, necrotic cells with membrane disruption and loss in ATP content cannot retain 201Tl.5 In cultured myocardial cells submitted to ischemia-like injury, as well as in isolated rat hearts under hypoxic and energy-depletion conditions, 201Tl uptake is dramatically reduced compared with controls. This decrease in 201Tl uptake is correlated to the amount of lactate dehydrogenase efflux and therefore to cell necrosis.6
Similarly, myocardial uptake of 99mTc-sestamibi is depressed in infarcted myocardium. This decrease is thought to be related to the diminution of sarcolemmal and mitochondrial membrane potentials.7 8 9 In a similar canine model of reperfused, acutely infarcted myocardium, 99mTc-sestamibi defect magnitude on planar images correlated with the extent of necrosis as assessed by histochemical analysis rather than reperfusion flow.21 Similarly, the ischemic-to-normal 99mTc-sestamibi myocardial uptake ratio by gamma-well counting correlated with extent of necrosis and was considerably lower than reperfusion flow.21 Similar findings have been observed with 99mTc-tetrofosmin.22
The exact uptake mechanism of 99mTc-teboroxime, a highly lipophilic perfusion agent, is unknown, but it is thought to bind nonspecifically to cell membranes. Like 99mTc-N-NOET, 99mTc-teboroxime uptake is not dependent on cellular metabolism and viability.23 24 25 However, results from studies examining the uptake of this agent in reperfused acute myocardial infarction are conflicting. Using a rabbit model, Heller et al10 found that 99mTc-teboroxime uptake in this setting reflects myocardial blood flow and is independent of myocardial viability. Conversely, in a study in pigs by Abraham et al,11 the infarct-to-normal 99mTc-teboroxime uptake ratio (0.85±0.32) is intermediate between myocardial blood flow ratios during occlusion (0.25±0.35) and after reperfusion (1.54±0.94) and thus could be dependent on both flow and viability. These divergent findings may result from species differences or from differing delays between tracer injection and image acquisition or sacrifice, a potentially major source of variation due to the rapid myocardial clearance of this agent.12
Although the precise mechanism of 99mTc-N-NOET myocardial uptake is unknown, this radiopharmaceutical has been demonstrated to associate with the lipophilic components of the myocytes,26 to have an extremely high myocardial retention in isolated perfused rabbit hearts,27 and to undergo increased clearance after severe cell membrane damage.27 In cultured newborn rat cardiomyocytes, 99mTc-N-NOET uptake has also been demonstrated to be independent of cellular metabolic status or ATP content.16
Thus, the data from the present study could be explained by the fact that in reperfused, acutely infarcted myocardium, 99mTc-N-NOET may bind to cell membranes, even if the myocytes are significantly damaged by ischemia and reperfusion. Within the first hour after reperfusion after acute myocardial infarction, microvascular integrity may permit almost complete reflow, as demonstrated in the present study.28 This reflow allows 99mTc-N-NOET to gain access to myocytes that may be in the phase of irreversible cell injury.4 Another potential explanation for high 99mTc-N-NOET uptake in zones of ongoing necrosis is binding of the tracer to neutrophils that aggregate in reperfused myocardium, ultimately contributing to the no-reflow phenomenon.28 The experimental findings of the present study do not necessarily contradict the diminution in 99mTc-N-NOET uptake observed in patients with chronic myocardial infarction.29 In this setting, no myocyte membranes available for 99mTc-N-NOET binding exist, and fibrosis and scar prevent the uptake of 99mTc-N-NOET.
Study Limitations
In the present study, 99mTc-N-NOET and
201Tl were injected either 1 or 3 hours after
reperfusion. It is possible that mild hyperemia was present
at the time when the tracers were injected, which may have resulted in
excess tracer uptake. However, it is important to point out that both
tracers were injected under the same flow conditions, yet their uptake
patterns were quite different.
Clinical Implications
Our experimental model of reperfused, acutely infarcted
myocardium suggests that 99mTc-N-NOET
uptake reflects more the magnitude of flow restoration rather than the
extent of myocardial salvage. Clinically, it remains to be determined
whether 99mTc-N-NOET imaging performed 15 to 20
minutes after injection in the setting of thrombolysis
in acute myocardial infarction can prove useful in assessing vessel
patency. Another clinical implication of this study is that
99mTc-N-NOET will not be a valid viability agent
in attempts to assess the degree of salvage very early after
coronary reperfusion. Myocardial perfusion agents such as
201Tl, 99mTc-sestamibi, and
99mTc-tetrofosmin would appear to be preferable
in this setting. Finally, studies comparing radionuclide imaging using
99mTc-N-NOET with other noninvasive techniques,
such as contrast echocardiography and contrast MRI
imaging, for accurate assessment of the degree of reflow after
reperfusion in the setting of acute myocardial infarction appear
warranted.
|
Acknowledgments |
|---|
This study was supported in part by a research grant from Cis-bio international. The authors thank Cis-bio international for its support of this experimental study.
Received September 29, 1999; revision received November 19, 1999; accepted December 6, 1999.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
-
Granger CB, White HD, Bates ER, Ohman EM, Califf
RM. A pooled analysis of coronary arterial
patency and left ventricular function after
intravenous thrombolysis for acute
myocardial infarction. Am J Cardiol. 1994;74:1220–1228.[Medline]
[Order article via Infotrieve]
-
Ellis SG, da Silva ER, Heyndrickx G, Talley JD,
Cernigliaro C, Steg G, Spaulding C, Nobuyoshi M, Erbel R, Vassanelli C.
Randomized comparison of rescue angioplasty with conservative
management of patients with early failure of
thrombolysis for acute anterior myocardial infarction.
Circulation. 1994;90:2280–2284.
[Abstract/Free Full Text]
-
Klootwijk P, Cobbaert C, Fioretti P, Kint PP, Simoons
ML. Noninvasive assessment of reperfusion and reocclusion after
thrombolysis in acute myocardial infarction.
Am J Cardiol. 1993;72:75G–84G.[Medline]
[Order article via Infotrieve]
-
Firschke C, Lindner JR, Wei K, Goodman NC, Skyba DM,
Kaul S. Myocardial perfusion imaging in the setting of coronary
artery stenosis and acute myocardial infarction using venous
injection of a second-generation echocardiographic
contrast agent. Circulation. 1997;96:959–967.
-
McCall D, Zimmer LJ, Katz AM. Kinetics of thallium
exchange in cultured myocardial cells. Circ Res. 1985;56:370–376.
[Abstract/Free Full Text]
-
Goldhaber SZ, Newell JB, Alpert NM, Andrews E, Pohost
GM, Ingwall JS. Effect of ischemic-like insult on myocardial
thallium-201 accumulation. Circulation. 1983;67:778–786.
[Abstract/Free Full Text]
-
Piwnica-Worms D, Kronauge JF, Delmon L, Holman BL,
Marsh JD, Jones AG. Effect of metabolic inhibition on
technetium-99m-MIBI kinetics in cultured chick myocardial
cells. J Nucl Med. 1990;31:464–472.
[Abstract/Free Full Text]
-
Piwnica-Worms D, Kronauge JF, Chiu ML. Uptake and
retention of hexakis (2-methoxyisobutyl isonitrile)
technetium(I) in cultured chick myocardial cells: mitochondrial
and plasma potential dependence. Circulation. 1990;82:1826–1838.
[Abstract/Free Full Text]
-
Piwnica-Worms D, Chiu ML, Kronauge JF. Divergent
kinetics of 201Tl and
99mTc-SESTAMIBI in cultured chick
ventricular myocytes during ATP depletion.
Circulation. 1992;85:1531–1541.
[Abstract/Free Full Text]
-
Heller LI, Villegas BJ, Reinhardt CP, Dahlberg ST,
Marcel R, Leppo JA. Teboroxime is a marker of reperfusion after
myocardial infarction. J Nucl Cardiol. 1996;3:2–8.[Medline]
[Order article via Infotrieve]
-
Abraham SA, Mirecki FN, Levine D, Nunn AD, Strauss W,
Gewirtz H. Myocardial technetium-99m-teboroxime activity in
acute coronary artery occlusion and reperfusion: relation to
myocardial blood flow and viability. J Nucl Med. 1995;36:1062–1068.
[Abstract/Free Full Text]
-
Stewart RE, Schwaiger M, Hutchins GD, Chiao PC,
Gallagher KP, Nguyen N, Petry NA, Rogers WL. Myocardial clearance
kinetics of technetium-99m-SQ30217: a marker of regional
myocardial blood flow. J Nucl Med. 1990;31:1183–1190.
[Abstract/Free Full Text]
-
Stewart RE, Heyl B, O’Rourke RA, Blumhardt R, Miller
DD. Demonstration of differential post-stenotic myocardial
technetium-99m-teboroxime clearance kinetics after
experimental ischemia and hyperemic stress.
J Nucl Med. 1991;32:2000–2008.
[Abstract/Free Full Text]
-
Ghezzi C, Fagret D, Arvieux CC, Mathieu JP, Bontron R,
Pasqualini R, de Leiris J, Comet M. Myocardial kinetics of TcN-NOET: a
neutral lipophilic complex tracer of regional myocardial blood flow.
J Nucl Med. 1995;36:1069–1077.
[Abstract/Free Full Text]
-
Vanzetto G, Calnon DA, Ruiz M, Watson DD, Pasqualini R,
Beller GA, Glover DK. 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.
Circulation. 1997;96:2325–2331.
[Abstract/Free Full Text]
-
Riou L, Ghezzi C, Mouton O, Mathieu JP, Pasqualini R,
Comet M, Fagret D. Cellular uptake mechanisms of
99mTcN-NOET in cardiomyocytes from
newborn rats: calcium channel interaction. Circulation. 1998;98:2591–2597.
[Abstract/Free Full Text]
-
Sinusas AJ, Watson DD, Cannon JM Jr, Beller GA. Effect
of ischemia and postischemic dysfunction on
myocardial uptake of technetium-99m-labeled methoxyisobutyl
isonitrile and thallium-201. J Am Coll Cardiol. 1989;14:1785–1793.[Abstract]
-
Smith WH, Watson DD. Technical aspects of myocardial
planar imaging with technetium-99m sestamibi. Am
J Cardiol. 1990;66:16E–22E.[Medline]
[Order article via Infotrieve]
-
Domenech RJ, Hoffman JI, Noble MI, Saunders KB, Henson
JR, Subijanto S. Total and regional coronary blood flow
measured by radioactive microspheres in conscious and
anesthetized dogs. Circ Res. 1969;25:581–596.
[Abstract/Free Full Text]
-
Parker PE, Bashour FA, Downey HF, Kechejian SJ,
Williams AG. Coronary hemodynamics during
reperfusion following acute coronary ligation in dogs. Am
Heart J. 1975;90:593–599.[Medline]
[Order article via Infotrieve]
-
Verani MS, Jeroudi MO, Mahmarian JJ, Boyce TM,
Borges-Neto S, Patel B, Bolli R. Quantification of myocardial
infarction during coronary occlusion and myocardial salvage
after reperfusion using cardiac imaging with technetium-99m
hexakis 2-methoxyisobutyl isonitrile. J Am Coll
Cardiol. 1988;12:1573–1581.[Abstract]
-
Glover DK, Ruiz M, Koplan BA, Watson DD, Beller GA.
Assessment of myocardial perfusion and viability with
technetium-99m-tetrofosmin in canine models of
coronary occlusion and reperfusion. J Nucl Med. 1999;40:142–149.
[Abstract/Free Full Text]
-
Kronauge JF, Chiu ML, Cone JS, Davison A, Holman BL,
Jones AG, Piwnica-Worms D. Comparison of neutral and cationic
myocardial perfusion agents: characteristics of accumulation in
cultured cells. Int J Rad Appl Instrum B. 1992;19:141–148.[Medline]
[Order article via Infotrieve]
-
Maublant JC, Moins N, Gachon P, Renoux M, Zhang Z,
Veyre A. Uptake of technetium-99m-teboroxime in cultured
myocardial cells: comparison with thallium-201 and
technetium-99m-sestamibi. J Nucl Med. 1993;34:255–259.
[Abstract/Free Full Text]
-
Rosenspire KC, Rumsey WL, Jurisson S, Hirth W, Narra
RK. [99mTc]teboroxime and
[99mTc]Cl(DMG)3B2 MP: binding characteristics
and metabolism of two [99mTc]BATOs
in blood and tissues. Nucl Med Biol. 1993;20:395–400.[Medline]
[Order article via Infotrieve]
-
Uccelli L, Giganti M, Duatti A, Bolzati C, Pasqualini
R, Cittanti C, Colamussi P, Piffanelli A. Subcellular distribution of
technetium-99m-N-NOET in rat myocardium.
J Nucl Med. 1995;36:2075–2079.
[Abstract/Free Full Text]
-
Johnson G III, Allton IL, Nguyen KN, Lauinger JM, Beju
D, Pasqualini R, Duatti A, Okada RD. Clearance of technetium
99m N-NOET in normal, ischemic-reperfused, and
membrane-disrupted myocardium. J Nucl
Cardiol. 1996;3:42–54.[Medline]
[Order article via Infotrieve]
-
Ambrosio G, Weisman HF, Mannisi JA, Becker L.
Progressive impairment of regional myocardial perfusion after initial
restoration of postischemic flow. Circulation. 1989;80:1846–1861.
[Abstract/Free Full Text]
-
Fagret D, Marie PY, Brunotte F, Giganti M, Le Guludec
D, Bertrand A, Wolf JE, Piffanelli A, Chossat F, Bekhechi D, Pasqualini
R, Machecourt J, Comet M. Myocardial perfusion imaging with
technetium-99m-Tc NOET: comparison with thallium-201 and
coronary angiography. J Nucl Med. 1995;36:936–943.
[Abstract/Free Full Text]
This article has been cited by other articles:
 |
|
 |
|
  L. M. Riou, S. Unger, M.-C. Toufektsian, M. Ruiz, D. D. Watson, G. A. Beller, and D. K. Glover Effects of Increased Lipid Concentration and Hyperemic Blood Flow on the Intrinsic Myocardial Washout Kinetics of 99mTcN-NOET J. Nucl. Med., July 1, 2003; 44(7): 1092 - 1098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Riou, C. Ghezzi, G. Vanzetto, A. Broisat, J.-P. Mathieu, R. Bontron, R. Pasqualini, and D. Fagret Verapamil Does Not Inhibit 99mTcN-NOET Uptake In Situ in Normal or Ischemic Canine Myocardium J. Nucl. Med., June 1, 2003; 44(6): 981 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takehana, G. A. Beller, M. Ruiz, F. D. Petruzella, D. D. Watson, and D. K. Glover 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 J. Nucl. Med., September 1, 2001; 42(9): 1388 - 1394. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||