Myocardial kinetics of 99m technetium-Q agents: studies in isolated cardiac myocyte, isolated perfused rat heart, and canine regional myocardial ischemia models.

OBJECTIVE: Based on reports of high cellular uptake and low plasma binding of nonreducible mixed ligand Tc(III) cations (Q complexes) and high linear uptake versus blood flow of 99mTc-Q3 in canine hearts, the authors hypothesized that the two Q complexes, 99mTc-Q63 and 99mTc-Q64, would have high cell uptake and better differentiation between ischemic and nonischemic myocardium compared with other 99mTc-based compounds. METHODS: Uptake and retention kinetics of 99mTc-Q63 and 99mTc-Q64 were measured in isolated rat cardiac myocytes, isolated perfused rat hearts, and intact canines and compared with previously reported Q-based compounds, a clinically available 99mTc perfusion agent (sestamibi), and 201Tl. RESULTS: Uptake of Q63, Q64, and sestamibi by isolated cardiac myocytes was similar. Maximum extraction (Emax) of Q64 by isolated perfused rat hearts was greatest among the 99mTc agents (P < 0.02), but net extraction (Enet) of Q64 was not different from Q63 or sestamibi 3 minutes after tracer injection. By 15 minutes, 201Tl Enet was lower than Q63, Q64, and sestamibi (P < 0.05). Among 99mTc agents, the uptake versus flow of Q3, Q63, and Q64 by canine heart was superior to Q12 and sestamibi (P < 0.05). CONCLUSIONS: The activity of Q63 and Q64 in the myocardium is related to actual myocardial blood flow over a broad, clinically relevant range of flows. The ischemic-to-normal zone activity distributions of Q63 and Q64 approximate actual flow in a manner more like that of 201Tl than sestamibi or Q12. These results provide a rational foundation in support of further evaluation of Q63 and Q64 in humans.

Reliability of technetium-99m Q12 and thallium-201 myocardial activity measurements after triphenyl tetrazolium chloride myocardial staining by perfusion.

RATIONALE AND OBJECTIVES: Investigations in animal models of severe myocardial ischemia or infarction use triphenyl tetrazolium chloride (TTC) staining to document infarction size histologically and to correlate these data with uptake measurements of radiolabeled tracers. Previously published data suggest that TTC staining itself has an important impact on myocardial tracer activity measurements. The authors hypothesized that TTC staining by perfusion has no significant effect on relative regional myocardial activity measurements of technetium-99m Q12 and thallium-201 in an open-chest canine model. METHODS: Eight dogs underwent left anterior descending artery occlusion for 2 hours with 30 minutes of reperfusion, followed immediately by injection of technetium-99m Q12 (n = 4) or thallium-201. Total myocardial activity was recorded in a dose calibrator, and regional myocardial samples were obtained by Cope needle biopsies from the ischemic and normal zones, both before and after TTC staining. RESULTS: The mean percent activity retention for the whole heart after perfusion staining with TTC was significantly reduced when compared to the preperfusion value for both technetium-99m Q12 and thallium-201. Regional measurements revealed no significant difference between the mean percent retention of technetium-99m Q12 in the ischemic and normal zones. After TTC perfusion, regional mean percent retention of thallium-201 was similar in the ischemic and normal zones. CONCLUSIONS: In a canine model of myocardial ischemia and infarction with reperfusion, TTC staining can be performed by coronary artery perfusion without significantly affecting comparative regional measurements of either technetium-99m Q12 or thallium-201. Whole heart tracer retention is significantly reduced by TTC perfusion staining, but thallium-201 is more affected than technetium-99m Q12.

Prediction of human transplantation arteriopathy and coronary events with lung/heart count ratios during intravenous dipyridamole thallium-201 imaging.

BACKGROUND: Cardiac allograft arteriopathy often limits long-term survival in transplantation recipients but has been difficult to detect by standard diagnostic methods. Because of the diffuse nature of transplantation coronary disease, we postulated that a lung/heart ratio during dipyridamole thallium imaging might better predict arteriopathy-related complications than diagnostic methods that detect discrete luminal stenoses. METHODS AND RESULTS: Sixty-six unselected heart transplantation recipients were evaluated with annual coronary arteriograms, endomyocardial biopsy, and intravenous dipyridamole thallium testing (initial study group). The mean lung/heart ratio on an anterior planar image was 0.40 for all patients; therefore <0.40 was arbitrarily defined as normal. After October 1992, 98 patients were tested (validation study group) and a lung/heart ratio cutoff of 0.40 was evaluated prospectively. Coronary end points were defined as (1) at least 1 coronary artery stenosis >/=50% of the luminal diameter, (2) sudden cardiac death, and (3) acute myocardial infarction. Stepwise logistic regression analysis was performed to identify independent predictors of future coronary end points. For the initial study group, the lung/heart ratio on the first annual thallium study was the only independent predictor of subsequent cardiac end points (0.47 +/- 0.13 [SD] with end points vs 0.38 +/- 0.11 without end points, P <.05). For the validation study group, independent predictors of subsequent coronary events included the lung/heart ratio and the radionuclide left ventricular ejection fraction. No patient with a lung/heart ratio <0.40 and a left ventricular ejection fraction >/=0.50 developed a cardiac event during 21 +/- 11 months of follow-up. CONCLUSIONS: A lung/heart ratio >/=0.40 on dipyridamole thallium testing is a sensitive predictor of coronary events after heart transplantation. Patients with heart transplantion who have a lung/heart ratio <0.40 and normal systolic left ventricular function are at low risk for subsequent coronary events and may not require annual surveillance by coronary arteriography.

Uptake of seven myocardial tracers during increased myocardial blood flow by dobutamine infusion.

RATIONALE AND OBJECTIVES: Direct comparison of myocardial perfusion tracers has been made difficult by variability in experimental models, and by a virtual absence of data comparing tracer uptake to myocardial blood flow under conditions of increased myocardial oxygen consumption, similar to what occurs with dynamic exercise. METHODS: Tracer uptake versus myocardial blood flow was evaluated for thallium-201 (201TI) and six technetium-99m (99mTc) myocardial-imaging agents in 24 open-chest canines with an occluded left-anterior descending coronary artery during dobutamine infusion. Data were fitted to the exponential model y = ax(1 - exp[-PSc/x]), where y is the tissue tracer/g normalized to normal (activity at 1 mL/minute/g) and x is the blood flow measured by the radioactive microsphere method. RESULTS: With dobutamine, myocardial tracer uptake was linear across a wide range of ischemic and hyperemic flows for each tracer. Based on the permeability surface area product, 201TI and 99mTc Q3 provided the best tracer estimate of myocardial blood flow (5.30+/-0.86 mL/minute/g, r = 0.91; 5.46+/-0.58 mL/minute/g, r = 0.94, respectively). Correlation coefficient (r) values for other tracers studied were 99mTc Q4 (r =0.93), 99mTc Q12 (r = 0.93), 99mTc sestamibi (r = 0.90), 99mTc tetrofosmin (r = 0.96), and 99mTc-N-Noet (r = 0.82). CONCLUSIONS: Of the 99mTc tracers examined under conditions of dobutamine-altered myocardial contractility, the myocardial uptake properties of 99mTc Q3 were most similar to those of 201TI.

Technetium-99m Q4: a prototype cationic perfusion radiotracer with myocardial washout.

Technetium-99m Q4 is derived from an existing mixed ligand myocardial tracer (99mTc-Q3) by the addition of an ester group to promote myocardial washout. Six subjects with single-vessel coronary disease documented by angiography and/or Q wave myocardial infarction documented by electrocardiography were studied with 99mTc-Q4 injection during exercise and with comparative thallium-201 tomography. Six healthy volunteers were also studied with 99mTc-Q4 imaging following injection at peak exercise. Tomographic images with 99mTc-Q4 and 201Tl each provided correct assessment of the presence or absence of coronary disease in 22 of 30 myocardial segments (73.3%). Six myocardial segments showed defect reversibility with 99mTc-Q4, whereas 14 segments showed reversibility with 201Tl, but the latter included three segments with no angiographic or electrocardiographic evidence of disease. In both normals and subjects with coronary artery disease, significant global washout of 99mTc-Q4 was observed over 4 h. For five patients with angiographic evidence of unrevascularized coronary artery stenosis, the ischemic to normal zone count ratio increased from 0. 782+/-0.107 at 45 min postexercise to 0.891+/-0.115 at 4 h postexercise (P = 0.016), suggesting occurrence of differential washout. It is concluded that addition of an ester group functionality to a previously studied mixed ligand cardiac tracer promotes global and regional myocardial tracer washout. Nevertheless, demonstration of perfusion defect reversibility with comparable frequency to that observed with 201Tl stress and reinjection images, required separate injections of 99mTc-Q4 at peak stress and at rest.

Technetium 99m glucarate: what will be its clinical role?

With publication of the studies by Khaw et al. and Beanlands et al. in this issue of the Journal, there is mounting evidence that 99mTc glucarate is taken up by infarcted but not by ischemic myocardium. The early myocardial distribution and rapid blood-pool clearance of 99mTc glucarate suggest important diagnostic potential in the very early detection of acute myocardial infarction and for the identification of successful acute revascularization therapy. To understand the full diagnostic implications of 99mTc glucarate accumulation in the myocardium, larger human trials are now needed. It will be critically important to document the capabilities of 99mTc glucarate to identify, early on, acute myocardial infarction in the presence of a persistently occluded infarct-related coronary artery in human beings.

Extraction and retention of technetium-99m Q12, technetium-99m sestamibi, and thallium-201 in isolated rat heart during coronary acidemia.

Technetium-99m Q12 and 99mTc-sestamibi are cationic lipophilic myocardial perfusion imaging tracers. Because myocardium in areas of ischemia becomes acidotic, experiments were designed to differentiate the effects of myocardial perfusate pH on radiotracer extraction and retention independent of substrate availability. We hypothesized that 99mTc-Q12 and 99mTc-sestamibi single-pass uptake and retention would be unaffected by a modest reduction in coronary perfusate pH. Isolated rat hearts were perfused at constant flow with Krebs-Henseleit buffer enriched with bovine red blood cells (20%). The indicator dilution method was used to measure the maximum extraction (Emax) and net extraction (Enet) of thallium-201 and 99mTc-Q12 (n = 8) or 201Tl and 99mTc sestamibi (n = 7) during baseline perfusion (pH = 7.4), during acidemic (pH = 6.7) perfusion, and during a restitution period with normal perfusate (pH = 7.4). 201Tl Emax (0.71+/-0.03) was greater than either 99mTc-Q12 or 99mTc-sestamibi Emax (0.27+/-0.02 and 0.26+/-0.01 respectively, P<0.0001). Acidemia significantly reduced 201Tl Emax (0.65+/-0.03, P<0.02) but not 99mTc-Q12 or 99mTc-sestamibi Emax (0.25+/-0.02 and 0.24+/-0.02 respectively). During control perfusion Enet of 201Tl was greater than that of 99mTc-Q12 at 3 and 5 min and greater than that of 99mTc-sestamibi at 3 min. 99mTc-Q12 Enet was less than 99mTc-sestamibi Enet at 3, 5, and 10 min. Acidemia decreased 201Tl and 99mTc-sestamibi Enet at 3, 5, and 10 min but had no effect on 99mTc-Q12 Enet. It is concluded that Emax of 99mTc-Q12 is less than that of 201Tl but is not different from that of 99mTc-sestamibi. Enet of 99mTc-Q12 is less than that of 99mTc-sestamibi.

Flow versus uptake comparisons of thallium-201 with technetium-99m perfusion tracers in a canine model of myocardial ischemia.

UNLABELLED: We investigated the myocardial flow kinetics of six putative radioperfusion agents (99mTc-Q3, 99mTc-Q4, 99mTc-Q12, 99mTc-sestamibi, 99mTc-tetrofosmin and 99mTcN-NOET) and 201Tl in a canine model of myocardial ischemia with pharmacologic coronary artery vasodilation. METHODS: In 31 open-chest dogs with acute coronary occlusion, dipyridamole (approximately 0.56 mg/kg) was infused intravenously, followed by a perfusion tracer injection and radioactive microspheres for myocardial blood flow (MBF) measurement. The paired data were normalized using three techniques; average, normal or maximum myocardial tracer activity and MBF. RESULTS: The upper limit of MBF obtained for the group of tracers ranged from 4.2 ml/min/g to 8.2 ml/min/g. There was a statistically significant (p < 0.0001) linear correlation (r = 0.87-0.98) between the normalized myocardial activity and the normalized MBF values of each of the tracers. The slope of the curve normalized by average for 201Tl (0.83) was greater than those for the 99mTc tracers, and the intercept (0.07) was lower than those for the 99mTc tracers. Slopes and intercepts for the 99mTc agents were as follows: 99mTc-Q3, 0.81 and 0.18; 99mTc-Q4, 0.61 and 0.41; 99mTc-Q12, 0.63 and 0.39; 99mTc-sestamibi, 0.62 and 0.34; 99mTc-tetrofosmin, 0.68 and 0.32; and 99mTcN-NOET, 0.71 and 0.29, respectively. CONCLUSION: In an anesthetized open-chest canine model of regional myocardial ischemia with dipyridamole induced hyperemia, 201Tl shows a more ideal relationship between tracer uptake and MBF than do the 99mTc-based agents. Of the various 99mTc-based imaging agents studied, the myocardial flow kinetics of 99mTc-Q3 appear to be closest to ideal. This relationship is maintained regardless of the normalization technique used. This may, in theory, imply a higher sensitivity in discerning ischemic from normal myocardium and a role in diagnostic nuclear imaging for 99mTc-Q3.

Effects of changes in atrioventricular gradient and contractility on left ventricular filling in human diastolic cardiac dysfunction.

The factors responsible for abnormalities in diastolic filling indexes as assessed by noninvasive testing in human beings have been extensively studied but are not completely understood. We therefore investigated left ventricular diastolic filling indexes by radionuclide angiography during right atrial pacing simultaneously with assessment of a directly measured left atrioventricular gradient and a time constant of isovolumic relaxation in 11 patients with hypertension and diastolic dysfunction. Loading conditions were altered with nitroprusside and phenylephrine, and contractility was improved by dobutamine infusion. The maximum left atrioventricular gradient at constant heart rates was determined by loading conditions and was not significantly affected by increases in contractility or an improvement in isovolumic relaxation rate. The peak filling rate according to radionuclide angiography was highly dependent on the atrioventricular gradient and was not affected by enhancement of the isovolumic relaxation rate.

Diagnostic utility of tomographic myocardial perfusion imaging with technetium 99m furifosmin (Q12) compared with thallium 201: results of a phase III multicenter trial.

BACKGROUND: Based on physical properties, 99mTc-labeled perfusion agents offer several advantages over 201Tl for myocardial perfusion imaging. The results of in vivo and experimental studies, along with preliminary experience in human subjects, have shown 99mTc-labeled furifosmin to be a promising new perfusion tracer. The purpose of this study was to evaluate the safety of a new myocardial perfusion agent, 99mTc-labeled furifosmin (Q12), and determine the concordance of furifosmin perfusion scintigraphy to 201Tl imaging. In addition, we sought to determine the normalcy rate of myocardial scintigraphy with furifosmin. METHODS AND RESULTS: One hundred fifty patients constituted the study group in this multicenter trial. Patients underwent exercise testing with furifosmin injected at peak exercise, and tomographic imaging was begun 15 to 30 minutes afterward. After a separate injection, resting images were obtained 3 to 4 hours later. Thallium scintigraphy was performed within 2 weeks of the furifosmin scans, after a similar exercise workload. Patients with a low likelihood of coronary artery disease (n = 39) also underwent furifosmin imaging. All images were processed and displayed in uniform manner and interpreted by a panel of readers. No adverse effects or clinically important laboratory alterations were related to furifosmin imaging. Image quality was slightly better with furifosmin than with thallium. The overall concordance between the perfusion studies was 86% (kappa value = 0.669). The normalcy rate for furifosmin scintigraphy was 100%. CONCLUSIONS: 99mTc-labeled furifosmin is a promising new 99mTc-labeled myocardial perfusion agent, providing diagnostic results similar to those obtained with 201Tl.

Effects of ouabain on technetium-99m-Q12 and thallium-201 extraction and retention by isolated rat heart.

UNLABELLED: The mechanisms of myocardial extraction and retention of the new cationic lipophilic radionuclide imaging agent 99mTc-Q12 are currently unknown. We hypothesized that 99mTc-Q12 has satisfactory single-pass extraction independent of active transport processes and longer cellular retention than 201Tl for rapid and sustained cardiac imaging to differentiate perfusion defects. METHODS: Isolated rat hearts were perfused at constant flow with Krebs-Henseleit buffer enriched with bovine red blood cells (30%-40%). The indicator dilution method was used to measure the single-pass maximum extraction (Emax) and net extraction (Enet(t)) of 201Tl and 99mTc-Q12 over 15 min during control perfusion (n = 11) and during normal (1 microM, n = 6) and high cardiotoxic (50 microM, n = 11) dose infusions of the digitalis glycoside, ouabain. RESULTS: The Emax of 201Tl was greater than 99mTc-Q12 Emax (0.73 +/- 0.01 and 0.29 +/- 0.01, respectively). At 3 min of perfusion, 201Tl Enet was greater than 99mTc-Q12 Enet (0.40 +/- 0.01 and 0.11 +/- 0.00, respectively). Between 3 and 15 min, 201Tl Enet was decreasing by a rate of 2% per minute while 99mTc-Q1 2 Enet was decreasing by less than 0.1 % per minute. Ouabain decreased 201TI Emax but did not change 99mTc-Q12 Emax. High-dose ouabain decreased 201Tl Enet at 3 min and 99-Tc-Q12 Enet at 10 and 15 min. CONCLUSION: Ouabain reduced 201Tl Emax but not 99mTc-Q12 Emax. Therefore, the cellular extraction process for 99mTc-Q12 is different from that of 201Tl. Since the Enet(t) of 99mTc-Q12 was reduced in the presence of high doses of ouabain while Emax was unchanged, 99mTc-Q12 extraction and retention appear to be controlled by different processes. Extraction and release kinetics of 99mTc-Q12 were not changed with a low dose analogous to the human therapeutic levels of ouabain.

Load independence of radionuclide diastolic filling measurements in acute coronary occlusion.

BACKGROUND: An accurate noninvasive method for measuring the effects of pharmacologic agents on active relaxation of the left ventricle would provide a valuable tool for monitoring the treatment of diastolic heart failure related to coronary artery disease. METHODS AND RESULTS: The time constant of isovolumic relaxation (T) and the left atrioventricular gradient were measured with micromanometer catheters and diastolic left ventricular filling variables were measured with radionuclide ventriculography in nine anesthetized, open-chest dogs with an acute coronary artery occlusion. Infusion of the positive inotropic drug dobutamine hydrochloride (5 to 10 micrograms/kg/min) resulted in a 35% shortening of T and a 37% increase in the radionuclide first-half filling fraction (both p < 0.05), but no change in the left atrioventricular gradient. Conversely, infusion of the alpha-adrenergic vasoconstrictor phenylephrine hydrochloride (20 to 40 micrograms/min) augmented left ventricular load, increasing the atrioventricular gradient by 45%, but had no significant effect on T or the first-half filling fraction. Infusion of the direct-acting vasodilator, sodium nitroprusside (80 to 120 micrograms/min), was accompanied by a 14% lengthening of T with a corresponding 28% decrease in the first-half filling fraction (both p < 0.05). CONCLUSION: In an anesthetized, open-chest canine model of acute myocardial ischemia, the radionuclide first-half filling fraction reflects pharmacologically induced changes in the lusitropic state of the left ventricle with relative independence of loading conditions.

Biokinetics and dosimetry analysis in healthy volunteers for a two-injection (rest-stress) protocol of the myocardial perfusion imaging agent technetium 99m-labeled Q3.

BACKGROUND: Trans (N,N'-ethylene bis(acetylacetoneimine)) bis(tris(3-methoxy-1-propyl) phosphine) 99mTc(III) (99mTc-Q3) has been developed for myocardial perfusion imaging. Biokinetic studies and dosimetry analysis have been completed for six healthy volunteers. METHODS AND RESULTS: The same-day two-injection protocol involved (1) an average rest injection of 241 MBq of 99mTc-Q3 followed by myocardial single-photon emission computed tomography (SPECT) at 15.0 minutes and a whole body (WB) scan at 1.5 hours; and (2) an average stress injection during treadmill exercise of 744 MBq of 99mTc-Q3 at 2.4 hours (postrest injection) followed by myocardial SPECT and additional WB scans at 1.5, 3.5, 6.5, and 21 hours poststress injection. Total urine was collected over 24 hours. Absolute organ activities were determined by conjugate counting methods. The two-injection data were simplified to a one-injection equivalent data set to facilitate dosimetry analysis. Decay corrected average percentage uptake values, plus or minus one standard deviation, for the myocardium were 1.4% +/- 0.2% at approximately 1.5 hours for both the postrest and poststress injections. The average biologic half-time for the myocardium was 26.4 hours. The highest organ uptake values included the gallbladder with 5.5% +/- 1.9% and the liver with 4.1% +/- 1.0% at the 1.5 hours poststress scan time. The sum of all gastrointestinal (GI) tract components was 18.8% +/- 9.4% at approximately 6.5 hours poststress injection (before any fecal elimination). The total 24 hour urine clearance was 17.1% +/- 2.4%. The gallbladder wall and upper large intestine wall received the highest doses at 0.024 and 0.023 mGy/MBq, respectively. CONCLUSION: The effective dose equivalent is estimated to be 0.01 mSv/MBq, which for an administration of 1110 MBq (30 mCi) is less than half that of a standard imaging protocol using 111 MBq (3 mCi) of 201Tl, and comparable to the published estimates for 99mTc-labeled sestamibi and 99mTc-labeled tetrofosmin (also normalized to 1110 MBq of administered activity). The 99mTc-Q3 exhibits myocardium uptake similar to that for these other two 99mTc agents.

Mechanisms, diagnosis, and treatment of diastolic heart failure.

Diastolic heart failure, in the absence of LV systolic dysfunction, is a common clinical condition that can be demonstrated in as many as one third of patients with congestive heart failure. Diastolic dysfunction caused by abnormalities in LV filling can be a result of many pathologic conditions, including hypertrophy, infiltrative cardiomyopathies, or myocardial ischemia. The major physiologic determinants of LV filling can be divided into cellular mechanisms, hemodynamic characteristics, and hormonal influences. Cellular mechanisms for impaired LV inactivation are determined by the handling of calcium within the myocyte during excitation-contraction-relaxation coupling. The hemodynamic characteristics of LV diastolic filling are determined by loading conditions, the time constant of isovolumic relaxation, heart rate, ventricular nonuniformity, pericardial restraint, myocardial elasticity, chamber compliance, and coronary blood flow. The sympathetic nervous system and the renin-angiotensin system are important modulators of diastolic filling, directly or indirectly. The diagnosis of heart failure is confirmed by a combination of clinical tests including invasive and noninvasive techniques, each of which has advantages and disadvantages. Treatment of medical conditions in which diastolic heart failure is a prominent component include pharmacotherapy with calcium channel antagonists, beta-adrenergic blocking agents, diuretic agents, and angiotensin-converting-enzyme inhibitors. Certain conditions associated with diastolic filling abnormalities such as pericardial disease or severe ischemic heart disease may be best managed by surgical or percutaneous intervention. Future research will include further delineation of the cellular mechanisms of active myocardial relaxation and clinical investigation into treatment directed at improving outcome.

Comparison of imaging properties of technetium 99m Q12 and technetium 99m Q3 in humans.

BACKGROUND: This study was a direct comparison of the imaging characteristics of 99mTc-labeled Q12 (99mTc-Q12) and 99mTc-labeled Q3 (99mTc-Q3) in the same patients. METHODS AND RESULTS: In 10 patients with known angiographic coronary artery anatomy, 99mTc-Q12 and 99mTc-Q3 myocardial imaging were performed. Tomographic myocardial imaging was started 15 minutes after tracer injection at rest and with treadmill exercise. Ratios of heart-to-lung and heart-to-liver activity were calculated from the anterior plane projections of the tomograms at 20 minutes after tracer injection. The presence or absence of angiographic coronary artery disease was correctly determined from 99mTc-Q12 images in 10 of 10 patients with 99mTc-Q12 and in 9 of 10 patients with 99mTc-Q3. The presence or absence of a greater than 50% stenosis in an individual coronary vessel was correctly predicted for 26 of 30 vessels with 99mTc-Q12 (87%) and in 27 of 30 vessels with 99mTc-Q3 (90%, p = NS vs 99mTc-Q12). Mean heart-to-lung activity ratio at rest was 1.50 for 99mTc-Q12 and 1.93 for 99mTc-Q3 (p < 0.01). Mean heart-to-liver activity ratio at rest for 99mTc-Q12 was 0.78 versus 0.54 for 99mTc-Q3 (p < 0.0001). CONCLUSIONS: In 10 patients with chest pain and angiographically defined coronary anatomy, 99mTc-Q12 and 99mTc-Q3 provided similar detection of coronary artery stenoses. At 20 minutes after tracer injection, heart-to-liver activity ratios were more favorable for 99mTc-Q12 than for 99mTc-Q3, but 99mTc-Q3 resulted in a more favorable ratio of heart-to-lung activity.

Comparison of technetium 99m Q12 and thallium 201 for detection of angiographically documented coronary artery disease in humans.

BACKGROUND: 99mTc-labeled Q12 (99mTc-Q12) is a new imaging agent that produces myocardial visualization in humans. This study examined the hypothesis that a 100-minute rest-exercise tomographic imaging protocol after injection of 99mTc-Q12 can be used to detect the presence or absence of coronary artery stenoses. METHODS AND RESULTS: Imaging with 201Tl and 99mTc-Q12 was performed in 20 patients with angiographically documented coronary artery disease and 10 "normal" subjects including two patients with chest pain and normal coronary arteriograms and eight subjects with a very low likelihood of occlusive coronary disease. 99mTc-Q12 was imaged beginning 15 minutes after injection at rest and with exercise. In the 20 patients, a corresponding myocardial defect was detected in blinded fashion in 18 with 201Tl and 17 with 99mTc-Q12 (difference not significant). Of 10 patients without evidence of coronary disease, nine had a normal 201Tl scan and eight had a normal 99mTc-Q12 scan (difference not significant). Agreement of 99mTc-Q12 and 201Tl imaging for detection of regional myocardial perfusion defects was excellent (kappa = 0.88). Identification of the presence or absence of angiographically documented coronary disease in individual coronary artery distributions was 80% and 82% for 201Tl imaging and 73% and 87% for 99mTc-Q12 (difference not significant). CONCLUSION: 99mTc-Q12, used in a rest-exercise sequence that can be completed in 100 minutes, provided identification of regional myocardial perfusion defects similar to that of 201Tl.

Myocardial uptake and kinetic properties of technetium-99m-Q3 in dogs.

UNLABELLED: We postulated that 99mTc-Q3, a cationic imaging agent, produces myocardial activity related to myocardial blood flow during myocardial ischemia and pharmacologic coronary artery vasodilation, and shows little or no myocardial redistribution over 4 hr after intravenous injection. METHODS: In six Group 1 dogs, the chest was opened, the left circumflex coronary artery was acutely ligated, and dipyridamole (0.32, 0.56 or 0.84 mg/kg) was infused into the right atrium, followed by 10 mCi of 99mTc-Q3. Myocardial blood flow was measured by radiolabeled microspheres. The animals were euthanized and 357 myocardial samples were assayed in a well counter for 99mTc activity. One week later, radiolabeled microsphere activity was counted and myocardial blood flow calculated. In nine Group 2 dogs, a variable occluder was placed around the left circumflex coronary artery and an ischemic level of circumflex blood flow was maintained constant over 4 hr as measured by an ultrasonic flow meter. Dipyridamole (0.56 mg/kg) was then infused into the right atrium followed by 10 mCi of 99mTc-Q3. Gamma camera images were acquired at 5, 15, 30, 60, 120 and 240 min following 99mTc-Q3 injection. Microsphere blood flow and endocardial biopsies (n = 6 dogs) were performed at 30, 60, 120 and 240 min following 99mTc-Q3 injection. RESULTS: In the Group 1 animals, 99mTc activity (y) was related to myocardial blood flow (x) from 0 to 6.1 ml/min/g by the relationship y = 0.83X + 0.18, r = 0.95, p = 0.0001. The scintigraphic ratio of myocardial perfusion defect zone counts-to-normal myocardial zone counts (0.54 +/- 0.05 at 30 min) remained constant over 4 hr, as did technetium counts from direct endocardial sampling. Scintigraphic count ratios allowed discrimination between perfusion defect and normal myocardial regions beginning at 5 min following 99mTc-Q3 injection. CONCLUSIONS: Over a range of myocardial blood flows from 0 to 6.1 ml/min/g, 99mTc-Q3 myocardial activity is related to myocardial flow at the time of tracer injection. Technetium-99m-Q3 shows no evidence of myocardial redistribution over a 4-hr period.

Comparison of technetium-99m-Q3 and thallium-201 for detection of coronary artery disease in humans.

UNLABELLED: Technetium-99m-Q3 is a myocardial imaging agent that produces prompt myocardial visualization in humans. METHODS: In 19 patients with angiographic coronary artery disease, 2 patients with no angiographic coronary artery stenosis greater than 50% of the luminal diameter and 6 healthy volunteers, exercise and resting myocardial imaging were performed with 99mTc-Q3 and also with 201Tl. Technetium-99m-Q3 imaging began 15 min after injection at rest and with exercise, in a complete imaging sequence that required less than 100 min. RESULTS: Overall accuracy for coronary disease detection was 78% (21 true-positive or true-negative studies among 27 study participants) by tomographic thallium imaging versus 89% for 99mTc-Q3 tomographic imaging (p = ns). Accuracy for detection of individual coronary stenoses was 75% (61 true-positive or true-negative coronary segment classifications among 81 total coronary segments) for 201Tl imaging and 83% for 99mTc-Q3 imaging (p = ns). CONCLUSIONS: Technetium-99m-Q3 when used in a rest-exercise sequence that can be completed in 100 min appears to provide comparable diagnostic accuracy to 201Tl for overall coronary disease detection and detection of individual coronary artery stenoses.

Kinetic properties of 99mTc-Q12 in canine myocardium.

BACKGROUND: 99mTc-Q12 is a new Tc(III) perfusion imaging agent that permits prompt myocardial visualization in humans. We postulated that 99mTc-Q12 myocardial activity is related to actual myocardial blood flow during conditions of myocardial ischemia and pharmacological coronary artery vasodilation and that 99mTc-Q12 shows little or no myocardial redistribution as long as 4 hours after intravenous injection. METHODS AND RESULTS: In seven anesthetized, open chest dogs, the left circumflex coronary artery was occluded, and dipyridamole (0.32 or 0.56 mg/kg) was infused into the right atrium, followed by 10 mCi of 99mTc-Q12. Myocardial blood flow was measured by radiolabeled microspheres. The animals were euthanized, and a total of 315 myocardial samples were assayed in a well counter for 99mTc activity. One week later, radiolabeled microsphere activity was determined, and myocardial blood flow was calculated. 99mTc activity (y) was related to myocardial blood flow (x) from 0 to 2 mL.g-1 x min-1 by the relation y = 0.64x + 0.35 (r = .88, P = .0001). In 14 additional anesthetized, open chest dogs, an occluder was placed around the left circumflex coronary artery, and an ischemic level of circumflex blood flow was maintained constant over 4 hours as measured by an ultrasonic flowmeter. Dipyridamole (0.56 mg/kg) was infused intravenously beginning 15 minutes after coronary occlusion and then followed by 10 mCi of 99mTc-Q12. Gamma camera images, hemodynamics, microsphere blood flow, and endocardial biopsies (latter in six dogs) were performed at 30, 60, 120, and 240 minutes after 99mTc-Q12 injection. Myocardial blood flow in the distribution of the left anterior descending artery decreased by 29.6% from 30 to 240 minutes (P < .05), whereas left circumflex blood flow increased by 40.4% from 30 to 120 minutes (P < .05) as the dipyridamole hemodynamic effects dissipated. Nevertheless, the ratio of myocardial perfusion defect zone counts to normal myocardial zone counts remained constant over 4 hours, as did the technetium counts from the needle biopsy endocardial samples. CONCLUSIONS: Over a limited range of myocardial blood flows from 0 to approximately 2 mL.g-1 x min-1, 99mTc-Q12 myocardial activity is related to actual myocardial flow at the time of tracer injection. 99mTc-Q12 shows no evidence of myocardial redistribution.