Identification of viable myocardium early after acute myocardial infarction using closed-loop arbutamine echocardiography: comparison with positron emission tomography.

OBJECTIVE: This study sought to evaluate the safety and efficacy of arbutamine echocardiography in identifying contractile reserve and predicting functional improvement early after acute myocardial infarction (AMI). METHODS AND RESULTS: Seventeen patients with first AMI underwent arbutamine echocardiography 48 to 96 hours after AMI. Arbutamine was infused by a closed-loop delivery device. The heart rate slope was 4 beats/min and the heart rate target was 20 beats/min above baseline heart rate. A follow-up echocardiogram was obtained one month later. N-13 ammonia and F-18 FDG positron emission tomographic (PET) imaging were performed 6 +/- 2 days after AMI, before coronary angiography. Mean duration of arbutamine infusion was 6 +/- 2 min. There was no complication and there were no major side effects. Myocardial viability was identified with PET in 15 of the 17 patients. Contractile reserve was observed in 10 patients during arbutamine infusion. Functional recovery was identified in 12 patients. Sensitivity, specificity and accuracy of PET and arbutamine echocardiography for predicting functional recovery were 100%, 40%, 76% and 67%, 80%, 84%, respectively. CONCLUSIONS: Low-dose arbutamine stress testing is safe early after AMI. Contractile reserve can be rapidly identified by echocardiography and is specific, but moderately sensitive for predicting reversible dysfunction.

The role of early measurement of nitrogen-13 ammonia uptake for predicting contractile recovery after acute myocardial infarction.

Previous studies have shown that the maintenance of cell membrane integrity and metabolism requires the persistence of residual myocardial blood flow. The purpose of this study was to assess the role of N-13 ammonia positron emission tomographic (PET) imaging performed early after an acute myocardial infarction for predicting functional recovery. Seventeen patients with an acute myocardial infarction were included in the study. Thirteen received thrombolytic therapy, 2 underwent immediate angioplasty of the infarct-related artery and 2 were treated with heparin. N-13 ammonia imaging was performed 6 +/- 2 days after the acute event and was followed by elective angioplasty in 13 patients. Using a 16-segment polar map display, regional N-13 ammonia uptake was expressed as a percentage of maximal segmental uptake and classified as normal (> 63%), moderately reduced (63-50%) and severely reduced (< 50%) based on values of tracer uptake obtained from healthy subjects. By echocardiographic assessment of regional wall thickening within 96 hours and at 1 month after the infarct, we examined the relationship between blood flow and functional outcome of myocardial segments in the infarct-related area. Regional wall thickening was graded on a 4-point scale: normal (1), hypokinesia (2), akinesia (3) and dyskinesia (4). Of 77 dyssynergic segments at baseline echocardiographic study, 43 had normal flow, 15 moderately reduced flow and 19 severely reduced flow. Segments with N-13 ammonia uptake > or = 50% demonstrated a significant improvement in wall thickening score at follow-up (p < 0.001), whereas segments with N-13 ammonia uptake < 50% showed no improvement in wall thickening scores (p < 0.001). The proportion of segments improving contractility by at least 1 score was significantly higher in the group of segments with N-13 ammonia uptake > 63%. The predictive value for defining functional recovery with segmental N-13 ammonia uptake > 63% was 86%. The predictive value for absence of recovery (uptake < 50%) was 54%. In conclusion, our data showed that early after an acute myocardial infarction N-13 ammonia imaging provides information regarding functional outcome.

Relation between contractile reserve and positron emission tomographic patterns of perfusion and glucose utilization in chronic ischemic left ventricular dysfunction: implications for identification of myocardial viability.

OBJECTIVES: This study sought to determine the incidence and extent of dobutamine-induced contractile reserve in myocardial regions characterized by classical and new positron emission tomographic (PET) patterns in patients with chronic ischemic left ventricular dysfunction. BACKGROUND: PET is considered the most accurate method for assessment of myocardial viability, which is traditionally identified by perfusion-metabolism mismatch. METHODS: In 23 patients, segmental wall thickening expressed by four echocardiographic scores at rest and during low dose (5 and 10 microg/kg body weight per min) dobutamine infusion and regional myocardial uptake of potassium-38 and fluorine-18 fluorodeoxyglucose (F-18 FDG) during glucose clamp were compared in 16 corresponding segments. RESULTS: Of a total of 368 segments, data analysis focused on 214 (58%) dyssynergic segments at baseline. Contractile reserve was identified with increasing incidence according to the six following PET patterns: 1) diminished perfusion and moderate reduction of F-18 FDG uptake (3 [11%] of 28 segments); 2) proportional reduction of perfusion and F-18 FDG uptake (10 [23%] of 43 segments); 3) perfusion-metabolism mismatch (19 [46%] of 41 segments); 4) preserved perfusion but moderate reduction of F-18 FDG uptake (13 [46%] of 27 segments); 5) preserved perfusion and F-18 FDG uptake (37 [59%] of 63 segments) compared with our normal database; and 6) normal perfusion but absolute increased F-18 FDG uptake (8 [73%] of 11 segments). In the latter category, only 7 of 24 segments had normal rest function. In dyssynergic segments with F-18 FDG uptake > or = 50% supplied by vessels with > or = 75% stenosis, improvement in contractility during dobutamine correlated with the presence of collateral channels. CONCLUSIONS: Myocardial regions with the traditional mismatch pattern of viability show contractile reserve in slightly < 50%. In segments with moderate reduction of F-18 FDG uptake, the contractile response to dobutamine is linked to the level of rest perfusion. Most segments with preserved perfusion and increased F-18 FDG uptake have impaired rest function, but contractile reserve is still present. These data suggest that in chronic ischemic left ventricular dysfunction, myocardial hibernation is a heterogeneous condition.

Immediate and long-term results of percutaneous coronary angioplasty in patients aged 70 years or older.

Percutaneous coronary angioplasty (PTCA) nowadays appears as an attractive alternative to coronary artery by-pass grafting not only in young adults, but also in elderly patients. The aim of this study was to investigate the primary success, complications and long-term efficacy of PTCA in a consecutive series of 63 patients aged 70 years or over. Results are analysed in comparison to a younger group of 423 subjects who were submitted to PTCA during the same period of time. In the older group, PTCA was applied to 108 lesions. The angiographic success rate was 88%. Primary success was 87%, with a majority (91%) of complete revascularization. Failure of the procedure was recorded in eight patients (13%). Complications of PTCA were observed in three patients, (among these: one death). The outcome was excellent: out of 55 patients with successful angioplasty, 52 (94.6%) were asymptomatic at the time of hospital discharge. At follow-up (close to one year), 84.6% of the patients remained asymptomatic. The comparison with the younger group of patients showed no difference in terms of primary success, failure rate or incidence of complications. We therefore conclude that PTCA can be performed with safety and efficiency in patients aged 70 years or over.

Effect of spinal cord stimulation on regional myocardial perfusion assessed by positron emission tomography.

Spinal cord stimulation (SCS) can relieve symptoms in patients with severe angina pectoris refractory to conventional medical or surgical therapy. This symptomatic improvement may result from decreased myocardial ischemia. To test this hypothesis, positron emission tomography (PET) and potassium-38 as a flow tracer were used in 8 patients for the quantitative evaluation of regional myocardial perfusion at rest and after exercise, before and during SCS. Potassium uptake was evaluated as myocardial clearance (flow times net extraction) in ml/min/100 g. Tomographic segments were categorized as nonaffected and affected on the basis of the absence or presence of arterial stenosis on coronary angiography and on the basis of thallium scintigraphic data. In nonaffected segments, before SCS, regional myocardial clearance significantly increased from rest (28 +/- 4) to exercise (47 +/- 13 clearance units; p less than 0.004). A similar increase occurred after SCS. In affected segments, before SCS, regional myocardial clearance barely increased (p = 0.065) from rest (26 +/- 6) to exercise (33 less than or equal to 12). In comparison, after SCS, the resting regional myocardial clearance was slightly elevated (29 +/- 8) reflecting an increased double product, but did not increase (p = 0.192) with exercise (34 +/- 12). However, the magnitude and duration of ST-segment depression decreased during treatment with SCS. Anginal pain occurred in all patients during control exercise, but was attenuated in all but one with SCS. These results indicate that SCS improves exercise-induced angina and electrocardiographic signs of ischemia but this influence does not appear to be mediated by changes in regional myocardial perfusion.

Imaging of myocardial metabolism by positron emission tomography.

Tracer techniques have provided new insight in cardiology by allowing noninvasive studies of myocardial perfusion, function, metabolism, and, more recently, ligand-receptor interaction. Positron emission tomography allows accurate quantification and the use of natural substrates labelled with 11C, 13N, or 15O. Myocardial metabolism is complex and utilizes a number of substrates, primarily fatty acids. Fatty acids utilization can be studied with 11C palmitate, while 11C acetate more selectively traces TCA cycle activity and reflects myocardial oxygen utilization. Glucose uptake can be traced using 18F deoxyglucose, a glucose analog that is a substrate for hexokinase but is not further metabolized. Flow and oxidative glucose metabolism are usually coupled, and thereby the uptake of FDG and perfusion tracers are usually similar. In myocardial ischemia, however, glucose utilization can persist due to anaerobic glycolysis, and its uptake is frequently enhanced. Clinical applications of the use of metabolic studies in patients with ischemic heart disease are presented.

Identification of viable myocardium by echocardiography during dobutamine infusion in patients with myocardial infarction after thrombolytic therapy: comparison with positron emission tomography.

To assess the presence of viable myocardium salvaged by coronary artery reperfusion, 17 patients with acute anterior myocardial infarction were studied. Each received intravenous thrombolysis within the first 3 h of symptoms and underwent two-dimensional echocardiography before and during dobutamine infusion (10 micrograms/kg per min) 7 +/- 4 days after admission and positron emission tomography 9 +/- 5 days after admission. Echocardiography and positron emission tomography were again performed 9 +/- 7 months later. Six comparable segments specific for the territory of the left anterior descending artery were selected for comparison of the two techniques. Wall thickening was evaluated by using an echocardiographic score index. Segmental perfusion and glucose uptake were measured and normalized to the peak activity. A ratio of glucose uptake to perfusion was calculated for each segment. Concordant interpretation of the two techniques was found in 79% of affected segments for both acute and follow-up studies. Positron emission tomography revealed the presence of viable myocardium in 11 patients (group 1); perfusion was within normal limits in 5 of these (group 1A). Myocardial thickening improved with dobutamine infusion in these five patients, the echocardiographic score index decreasing from 12 +/- 2 at rest to 7.8 +/- 1.3 during dobutamine infusion (p = 0.003). Functional recovery was demonstrated in all five patients (follow-up score index 7.4 +/- 1.7). Six patients exhibited decreased perfusion but an abnormally high glucose to perfusion ratio (group 1B); their score index improved with dobutamine from 14.8 +/- 2.2 to 12 +/- 2.1 (p = 0.05), but late functional recovery was found in only one of the six patients (mean follow-up score index in group 1B 16 +/- 1.7). In the six remaining patients in whom no viable myocardium was detected with positron emission tomography (group 2), the echocardiographic score index did not change with dobutamine (15 +/- 0.9 to 14.7 +/- 0.8, p = NS) and there was no functional recovery (follow-up score index 15.5 +/- 1.0). Echocardiography during dobutamine infusion is a promising method to unmask viable myocardium in acute myocardial infarction. Early recovery of perfusion in the area at risk is associated with a good functional outcome, whereas a high glucose to perfusion ratio indicates jeopardized myocardium that frequently loses viability.

[Methods and clinical applications of positron emission tomography in endocrinology]. / Méthodologie et applications cliniques en endocrinologie de la tomographie à émission de positons.

Positron emission tomography (PET) allows to detect in coincidence photons issued from annihilation between positrons and electrons nearby situated. Tomographic detection (plane by plane) and tomographic reconstruction will lead to the quantitation of radioactive distribution per voxel, in the organ of interest. Recent tomographs can acquire simultaneously several transaxial slices, with a high sensitivity and a spatial resolution of 3-5 mm. Commonly used positron emitters have a short half-life: 2, 10, 20 and 110 min for 150, 13N, 11C and 18F, respectively. The use of these isotopes requires on line production of radionuclides and synthesis of selected molecules. In endocrinology, PET allows among others to study noninvasively the receptor density of hormone-dependent neoplasms such as breast, uterus, prostate tumors and prolactinomas. These last tumors represent a particular entity because of several combined characteristics: high turnover rate of amino acids, high density of dopaminergic receptors and response to bromocriptine (analogue of dopamine inhibiting the secretion of prolactin) in relation to the level of receptors. Because PET permits to evaluate the density of dopaminergic receptors and the metabolism of amino acids, theoretical response of the prolactinoma to bromocriptine can be predicted, the achieved therapeutic efficacy can be estimated and the long-term follow up of tumor growth can be assessed. This example illustrates the clinical value of PET in endocrinology.

Effect of exercise on the leg distribution of C15O2 and 15O2 in normals and in patients with peripheral ischemia: a study using positron tomography.

In order to evaluate regional muscle blood flow and oxygen utilization, we study with positron emission tomography (PET) the distribution of C15O2 and 15O2 in 17 subjects: 5 normals (24 +/- 3 years) and 12 patients (63 +/- 13.5 years). C15O2 and 15O2 are inhalated with a steady-state technique. Positron tomograms are recorded in supine position at the greatest diameter of the leg. Exercise consists in simultaneous ankle flexions. In all normals, C15O2 and 15O2 are distributed homogeneously and symmetrically in both legs. At rest, they concentrate in the region of vascular pedicle. After exercise, C15O2 and 15O2 are electively distributed in the anterolateral region of the leg. In patients, this pattern of distribution is similar but asymmetrical. Moreover, the regional uptake of C15O2 and 15O2 often dissociates. In conclusion, C15O2 and 15O2 allow to study repeatedly muscle blood flow and oxygen utilization in patients with peripheral ischemia, both at rest and after exercise. The broad spectrum of pathological changes observed in this study needs further metabolic investigations.

[Regional blood flow and oxygen consumption in the leg muscles of normal subjects and in those with arterial insufficiency. Study of the distribution of C15O2 and of 15O2 using positron emission tomography]. / Débit sanguin régional et extraction de l'oxygène dans les muscles de la jambe chez le sujet normal et l'insuffisant artériel. Etude de la distribution du C15O2 et de l'15O2 par tomographie à émission de positons.

We first studied the distribution of radioactivity during continuous inhalation of C15O2 and 15O2 in traverse tomograms of the greatest diameter of legs, at rest and immediately after exercise (ankle flexions). C15O2 and 15O2 were distributed homogeneously and symmetrically in both legs of normal subjects at rest. The activity accumulated in the anterolateral region after exercise. In patients, this pattern of distribution was similar but asymmetrical, depending on the arterial pathology. No systematic distribution of either C15O2 or 15O2 was observed. In a second step, we studied quantitatively blood flow (F), oxygen uptake (R) and oxygen extraction (E) in 11 subjects: 5 normals (23 +/- 1 years) and 6 patients (60 +/- 11 years) suffering from unilateral intermittent claudication. We used the bolus inhalation technique of C15O2 and 15O2. In the normal leg at rest, ranges were 2.5 to 8.0 ml/min.hg for F, 0.9 to 21.3 mumol/min.hg for R and 3.6 to 33.4% for E. In the pathological leg at rest, ranges were 3.7 to 11.3 ml/min.hg for F, 3.8 to 10.6 mumol/min.hg for R and 7.1 to 24.5% for E. After exercise, ranges were 6.4 to 62.8 ml/min.hg for F, 66.0 to 386.3 mumol/min.hg for R and 29.2 to 89.5% for E in both legs. There was no straight difference between normal and pathological legs soon after exercise. This study allows us to expect that the demonstration of such a difference implies a longer delay of data acquisition following the slow post-ischemia recovery.

Automated production of potassium-38 for the study of myocardial perfusion using positron emission tomography.

The 35Cl(alpha, n)38K nuclear reaction was developed for the routine cyclotron production of repeated multimillicurie batches of 38K for dynamic studies of regional tissue perfusion with positron emission tomography. The objective is to make this isotope available as an alternative to the use of [13N]NH3 and 82Rb for the investigation of flow in experimental and clinical use. A sodium chloride powder target mounted on a water-cooled nickel backing is bombarded with 26 MeV helium-4 ions at a maximum beam current of 25 microA. The target is remotely disconnected from the bombardment port, transported to a hot cell and entirely processed by a computer-controlled system within a total time of less than 4 min. The final pyrogen-free isotonic and sterile solution of 38K has a radionuclidic purity of more than 99.99%. A typical yield of 19 +/- 2 mCi of 38K is obtained at the end of a 30 min bombardment at 10 microA. The production rate at saturation can therefore be estimated to 2.05 +/- 0.2 mCi/microA.

Preparation and evaluation of a hydrous tin(IV) oxide 82Sr/82Rb medical generator system for continuous elution.

Hydrous tin(IV) dioxide in the Na+-form appears to be the most efficient inorganic exchanger for a reliable and versatile clinical 82Rb generator. Continuous elution with a commercial physiological NaCl solution yields 82Rb ranging between 10 and 40% at a flow rate as low as 3 to 10 mL/min respectively. At the same time the Sr breakthrough is less than 1.6 10(-6)%/mL. A clinical generator loaded with 100 mCi 82Sr (150 mCi 85Sr) and continuously eluted for 3 min at a typical flow rate of 5 mL/min yields 40 mCi of 82Rb, 8 nCi of 82Sr and 11 nCi of 85Sr. The total absorbed radiation dose for 40 mCi 82Rb administered is primarily due to 82Rb and has been estimated for the three principal target organs as 760 mrad for the kidneys, 520 mrad for the heartwalls and 276 mrad for the lungs. The 82,85Sr contribution to the dosimetry has been shown to be negligible. The absence of radiolysis with generators loaded with high level of 82Sr was demonstrated by the excellent reproductibility of continuous elution properties of the generator during its practical shelf-life estimated to 5-6 weeks of clinical use which would require more than 30 L of eluent.

Direct effects of smoking on the heart: silent ischemic disturbances of coronary flow.

Cigarette smoking is strongly associated with ischemic heart disease and acute coronary events. The effect of smoking a single cigarette on regional myocardial perfusion was studied in 13 chronic smokers with typical stable angina pectoris using positron emission tomography and rubidium-82 (82Rb). Findings were compared with the effects of physical exercise. After exercise, 8 patients (61%) had angina, ST depression and abnormal regional myocardial perfusion. Uptake of 82Rb increased from 49 +/- 8 to 60 +/- 7 in remote myocardium, but decreased from 46 +/- 3 to 37 +/- 5 in an ischemic area. The remaining 5 patients (39%) had homogeneous increases in 82Rb uptake without angina or ST depression. After smoking, 6 of the 8 patients with positive exercise test responses had a decrease in 82Rb uptake, from 47 +/- 3 to 35 +/- 6 in the same segment of myocardium affected during exercise. However, in contrast to exercise, the events during smoking were largely silent. The absolute decreases in regional 82Rb uptake after smoking occurred at significantly lower levels of myocardial oxygen demand than after exercise. This suggests that an impairment of coronary blood supply is responsible. Thus, in smokers with coronary artery disease, each cigarette can cause profound silent disturbances of regional myocardial perfusion that are likely to occur frequently during daily life. Such repeated insults may represent an important mechanism linking smoking with coronary events.

Regional myocardial and organ blood flow after myocardial infarction: application of the microsphere principle in man.

A physiologic means of measuring the distribution of cardiac output and regional myocardial blood flow has been developed that uses human albumin microspheres labeled with carbon-11 (11C) and external detection with positron emission tomography. Ten patients with previous myocardial infarction were studied to investigate the level of blood flow in normal and infarcted segments of the heart. After diagnostic catheterization, 4 to 6 mCi of 11C on 2 to 3 million sterile microspheres (15 to 20 micron) were mixed and injected into the apex of the left ventricle during timed withdrawal of arterial blood to obtain reference flow values. Regional activity in brain, heart, lungs, liver, spleen, and kidneys was measured tomographically. Blood flow was calculated based on the relationship between total activity in a reference flow and tissue activity in tomograms of each organ (ml/min/100 g). No adverse effects were noted after injection of the microspheres. Successive myocardial tomograms showed no loss of activity. There were no significant differences in flow values in matched regions of paired organs. Mean cerebral flow was 52.4 +/- 10.0 ml/min/100 g in the frontal lobes, 54.4 +/- 8.8 in the temporal lobes, 67.6 +/- 8.2 in the occipital lobes, and 53.0 +/- 9.4 in the basal ganglia. Flow was 16.0 +/- 8.4 ml/min/100 g (range 0 to 40.0) in the center of infarcted myocardium and 82.0 +/- 32.0 in the remote segments. This method meets most of the demands for use of microspheres to measure tissue blood flow. The wide range of flow values in infarcted myocardium may be a function of infarct size, spatial resolution, or pathologic evidence of islands of viable tissue. Patients with angina had high flow values in the infarcted segment, whereas those with heart failure had significantly lower values. Surviving myocardium in the region of the infarct may need to be considered if patients complain of angina, particularly when treatment is aimed at preserving ventricular function.

Myocardial blood flow and glucose uptake after myocardial infarction.

Position emission tomography can picture the distribution of flow tracers as well as of metabolic substrates or analogs. Studies of the distribution of these tracers allow to infer information about regional myocardial clearance (flow X extraction) and substrate utilization. In a study of 32 patients after myocardial infarction, we have contrasted flow and substrate utilization to demonstrate ischemic but viable myocardium in the arterial territory of the infarct in a number of patients also specially after fibrinolytic reperfusion. Restoration of blood flow to the ischemic but viable myocardium through coronary bypass or dilatation improves flow from 56.3% to 84.2% of control and restores substrate utilization. In another group of 32 patients studied with the Strontium-82/Rubidium-82 generator, we have demonstrated perfusion changes both in the myocardial infarct area and at a distance. These changes predominate in patients with multiple vessel disease. Combined PET studies of flow and substrate utilization are new tools to study early intervention after myocardial infarction and to document the benefits of revascularization.

[Prognostic significance of the type A behavior pattern]. / Influence pronostique du modèle de comportement de type A.

In a clinical study on cardiac rehabilitation, the authors point out that the outcome of coronary heart disease patient is profoundly conditioned by the intensity of Pattern A behavior. The need to modify this behavior is evident.

Transient ST-segment depression as a marker of myocardial ischemia during daily life.

Patients with angina and coronary artery disease (CAD) have many episodes of transient ST-segment depression during ordinary daily life, and these are often asymptomatic. To investigate this signal as a marker of myocardial ischemia, 30 patients with chronic stable angina and CAD underwent positron tomography, recording the regional myocardial uptake of rubidium-82, pain and ST-segment changes before, during and after 59 technically satisfactory exercise tests, 35 cold pressor tests and 22 episodes of unprovoked ST depression. Exercise resulted in 53 episodes of ST depression with angina and in 5 episodes without pain. After cold pressor tests, there were 3 episodes of ST depression and pain and 12 of painless ST depression. Only 9 episodes of unprovoked ST depression were accompanied by pain. Tomography showed independent evidence of ischemia in 63 (97%) of the total 65 episodes of ST depression with angina and in all 30 episodes of painless ST depression. In each patient perfusion defects occurred in the same myocardial segment during painful and painless ST depression and responses were significantly different from those in 16 normal subjects studied in the same way. These findings support the use of transient ST depression in continuous monitoring to assess the activity of CAD, but only in patients with typical angina pectoris, ST depression during exercise and proved CAD. They strengthen the evidence derived from ambulatory monitoring for a wider picture of the disease than is generally appreciated, with more frequent episodes of silent myocardial ischemia than of angina pectoris.

Silent myocardial ischaemia due to mental stress.

Patients with angina and coronary disease have many episodes of symptomless transient myocardial ischaemia, most of which cannot be explained by physical exertion. 16 patients with typical stable angina pectoris were examined to test the hypothesis that these episodes can be triggered off by ordinary daily events, such as changes in mental activity. Regional myocardial perfusion and ischaemia were assessed by measurement of the uptake of rubidium-82 with positron tomography after mental arithmetic and physical exercise. With mental arithmetic, 12 (75%) patients had abnormalities of regional perfusion, accompanied in only 6 by ST-segment depression and in 4 of these 6 by angina, leaving 6 patients with perfusion abnormalities but neither pain nor electrocardiographic changes. After exercise, all the patients showed abnormal regional myocardial perfusion in the segments that became ischaemic with mental arithmetic. This was accompanied by ST depression in all and angina in 15. The association between mental activity and myocardial ischaemia may operate frequently during everyday life and may explain many of the transient and symptomless electrocardiographic changes in patients with coronary disease.

Validation of quantitation of regional myocardial blood flow in vivo with 11C-labeled human albumin microspheres and positron emission tomography.

Use of radiolabeled microspheres is a standard method to measure regional myocardial perfusion in animals. Human albumin microspheres have been given safely to patients, but positron-emitting 68Ga-labeled human albumin microspheres are characterized by an unstable radiolabel. A new labeling procedure that covalently binds 11C (t1/2 = 20.3 min) to human albumin microspheres via 11CH3I was developed. Seven open-chest and two closed-chest dogs were studied. Reference and 11C-labeled human albumin microspheres (2 to 25 mCi) were both injected into the left atrium. Positron tomographic images were obtained of the myocardial distribution of the 11C-labeled microspheres. Timed arterial withdrawal was used for both reference gamma-labeled microspheres and 11C-labeled human albumin microspheres. Myocardial tissue samples matched to tomographic slices were well-counted for calculation of reference values of regional myocardial perfusion. Serial venous blood samples for residual 11C activity of 30 and 60 min after injection were less than 1% of the myocardial 11C concentration demonstrating a stable 11C bond to the human albumin microspheres. Regional myocardial perfusion calculated by this technique correlated well with values obtained with reference microspheres (r = .97) over a range of 0.2 to 3.5 ml/min/g. Correction for wall thickness improved the slope of the regression equation from y = 0.71 x -0.03 to y = 0.88 X -0.05. Thus, 11C human albumin microspheres are stable radiochemically and can be used as a quantitative measure of regional myocardial perfusion.