Indium-111 Monoclonal Antimyosin Research Articles

Coronary endothelial dysfunction and myocardial cell damage in chronic stable idiopathic dilated cardiomyopathy

Impairment of endothelium-dependent vasodilatation in response to acetylcholine reflects an abnormal endothelial function. Labelled indium-111 monoclonal antimyosin antibodies enable detection of myocardial cell damage. We analysed whether endothelial dysfunction correlates with myocardial antimyosin uptake in a selected group of patients with idiopathic dilated cardiomyopathy. Methods: Twenty-two consecutive patients with chronic stable idiopathic dilated cardiomyopathy (18 males and four females) were included. The duration of heart failure symptoms was 46±34 months. At inclusion, the functional class of New York Heart Association was 2.1±0.7. Endothelial function was evaluated using intracoronary graded concentrations of acetylcholine. Vasomotor responses of the left anterior descending coronary artery were measured by quantitative coronary analysis. Myocardial uptake of antimyosin antibodies was quantified by means of a heart-to-lung ratio (HLR). Results: Eighteen patients showed endothelial dysfunction (82%) and the remaining four patients showed a normal endothelial function. There were no statistically significant differences between patients with and without endothelial dysfunction in relation to clinical, echocardiographic and hemodynamic parameters. In addition, these variables did not correlate with the magnitude of the vasomotor response to acetylcholine. Eighteen patients (82%) showed abnormal antimyosin uptake; 15 of them (83%) showed endothelial dysfunction. The global mean HLR of antimyosin uptake was 1.73±0.24. The coronary vasomotor response to acetylcholine correlated with the intensity of uptake of antimyosin antibodies ( r=−0.45, P<0.04). Conclusions: Coronary endothelial dysfunction and myocardial antimyosin uptake was found in a high percentage of patients with chronic stable idiopathic dilated cardiomyopathy. The abnormal vasomotor response seems to be related to the degree of myocardial damage.

Myocardial indium-111 antimyosin uptake after uncomplicated coronary artery bypass surgery

The prevalence of myocardial damage after coronary artery bypass grafting is related to the criteria of its evaluation. Indium-111 monoclonal antimyosin antibody scintigraphy has been shown to be highly sensitive and specific for even small areas of myocardial necrosis or injury like those of myocarditis or transplant rejection. Our purpose was to evaluate, by using this method, myocardial damage after uncomplicated coronary artery bypass grafting. Uptake of this radio tracer was evaluated after coronary artery bypass grafting in 14 informed and consenting consecutive patients without previous myocardial infarction, with no post-surgical complications and a favorable postoperative course, following coronary artery bypass grafting for stable angina pectoris. Monoclonal antimyosin antibody indium-111 74 MBq (Myoscint Centocor) was injected on the third postoperative day; planar images in the anterior, left anterior oblique 45 ° and 70 ° projections were obtained 24 and 48 h later and analyzed for myocardial uptake. Indium-111 antimyosin uptake was present in 10 out of 14 patients (71.4%); it was diffuse in 6 and localized in 4. The ratio of the maximal counts in the myocardium to the counts in the adjacent lung background was measured and found elevated: 1.94 ± 0.23, higher than the normal values reported in the literature. Indium-111 antimyosin uptake was clear in a group of patients after uncomplicated coronary artery bypass grafting. No correlation was observed between indium-111 antimyosin uptake or heart to lung ratio and creatine kinase, creatine kinase isoenzyme MB, glutamic oxalacetic transferase levels, duration of cardiopulmonary bypass or aortic cross-clamp time, while elevated serum β myosin heavy chain fragments (IRMA Pasteur) were observed (1378 ± 238 μU/1). This study suggests that some degree of myocardial damage, though silent, is common after coronary artery bypass grafting.

Natural evolution of antimyosin scan and cardiac function in patients with acute myocarditis

Indium-111 monoclonal antimyosin antibody imaging is a convenient method to diagnose acute myocarditis. The present study examined the natural evolution of a positive antimyosin scan in 10 patients with acute myocarditis, in relation to left ventricular ejection fraction. All patients underwent myosin-specific monoclonal antibody imaging and radionuclide ventriculography; in all patients endomyocardial biopsy was performed. Repeat assessment of left ventricular function and antimyosin uptake was performed 1, 2 and 6 months later. A heart-to-lung ratio was used to quantify antimyosin uptake. Heart-to-lung ratio in patients with myocarditis was 2.12 ± 0.31, significantly higher than that observed in eight controls (1.35 ± 0.08, P < 0.001). During follow-up 2.2 repeat scans per patient were performed. Heart-to-lung ratio normalized (< 1.6) within 1 month in four patients, within 2 months in one patient and within 6 months in two patients; three patients continued to have a positive antimyosin uptake at 6 months, suggesting ongoing myocardial necrosis. At the end of follow-up, ejection fraction improved by > 5% in four patients; normalization or persistence of tracer uptake could not predict an improvement of ejection fraction. It is concluded that antimyosin scintigraphy is useful for diagnosing myocarditis in its subacute or chronic stage during which unknown or immune mechanisms may be in operation. An improvement in left ventricular function cannot be predicted on the basis of persistence or not of tracer uptake.

Myocardial uptake of indium-111 antimyosin after coronary angioplasty. Relationship with the total burden of ischaemia.

Indium-111 antimyosin scintigraphy was performed in 24 consecutive patients after percutaneous transluminal coronary angioplasty to assess whether repeated periods of ischaemia during balloon inflation results in myocardial cell damage even after a successful procedure. Patients with unstable angina, prior myocardial infarction and whose procedure was complicated were excluded. Indium-111 monoclonal antimyosin antibodies (80 MBq) were injected 24 h after coronary angioplasty and planar images were collected 24 h later. The relative antimyosin uptake was assessed subjectively and by a heart/lung count density ratio. In addition, the intracardiac gradient of activity was assessed by a count density profile analysis of the cardiac region of interest to distinguish better the focal as opposed to the diffuse antimyosin uptake. The antimyosin uptake index was calculated by multiplying the heart/lung ratio to the intracardiac gradient of activity. After coronary angioplasty, nine patients had minor ST-T wave changes on the surface ECG, but no patient demonstrated a new Q wave. Only three patients showed a mild rise in cardiac enzyme (CK-MB) serum levels. Indium-111 antimyosin uptake (heart/lung > 1.55) was present in eight patients (33%) and was intense (heart/lung > 1.9) in five (21%). Antimyosin uptake was always seen in myocardial segments corresponding to the treated coronary artery. Patients with a positive antimyosin scan had a longer duration of balloon-induced ischaemia compared with patients with no evidence of antimyosin uptake (541 +/- 211 vs 331 +/- 137 s, P < 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Indium 111—Monoclonal Antimyosin Antibody and Magnetic Resonance Imaging in the Diagnosis of Acute Lyme Myopericarditis

Lyme borreliosis is a tick-borne multisystem disorder that may present as self-limiting early or persistent chronic diseases of the skin, nervous system, joints, heart, and other organs. Cardiac involvement has mainly been reported as acute atrioventricular conduction disturbances or transient ventricular dysfunction. We treated a patient with clinical signs of acute myopericarditis and serologic evidence of Lyme borreliosis confirmed by silver staining of endomyocardial biopsy specimens and indium 111-monoclonal antimyosin antibody scan, which we believe has not been reported previously. Additionally, magnetic resonance imaging revealed epicardial and myocardial areas of increased intensity. Indium 111-monoclonal antimyosin antibody scanning and magnetic resonance imaging might play an additional important role in assessing and confirming the diagnosis of Lyme carditis in the presence of clinical symptoms and positive serologic findings.

Indium 111-monoclonal antimyosin antibody and magnetic resonance imaging in the diagnosis of acute Lyme myopericarditis

Indium 111-monoclonal antimyosin antibody and magnetic resonance imaging in the diagnosis of acute Lyme myopericarditis

Blood flow-dependent uptake of indium-111 monoclonal antimyosin antibody in canine acute myocardial infarction

Objectives. The relation of myocardial blood flow and indium-111 (111In) antimyosin antibody uptake was studied by inducing myocardial infarction in 18 dogs, 8 with closed chest left anterior descending artery balloon occlusion for 3 h followed by reperfusion (group A) and 10 dogs with open chest left anterior descending artery ligation (without reperfusion, group B).Background. The relation of antimyosin uptake to myocardial injury has been documented. However, its relation to tracer delivery by myocardial blood flow has not been studied and has been assumed to be independent.Methods. Indium-111 antimyosin antibody, 2 mCi, was injected 20 min after reperfusion and 3 h after coronary artery ligation in groups A and B, respectively. Regional blood flows were determined by radiolabeled microspheres during occlusion and 24 h later in both groups. On day 2, dogs were killed after risk zone delineation with gentian violet. The heart was excised and stained with triphenyltetrazolium chloride solution and graded for increasing severity of tissue injury based on extent of staining. Microsphere activity and 111In antimyosin activity were measured in control tissue (grade 1), noninfarct tissue at risk (grade 2), mixed tissue (grade 3), infarct tissue (grade 4) and hemorrhagic infarct tissue (grade 5, present only in group A dogs). count activity was normalized to that of the mean value in control tissue (grade 1) and expressed as a ratio of activity.Results. Indium-111 astimyosin activity was high in triphenyltetrazolium chloride grade 4 tissue in both groups but was attenuated in grade 4 tissue in group B dogs (10.6 ± 5.1 vs. 5.0 ± 4.5; p < 0.05 group A vs. group B), which had lower blood flow on day 2 (0.51 ± 0.36 vs. 0.23 vs. 0.22; p < 0.01). Normalizing 111In antimyosin activity for blood flow on day 2 resulted in equivalent 111In antimyosin uptake for infarct tissue (32.6 ± 21.6 vs. 36.6 ± 29.8 for group A vs. group B; p = NS).Conclusions. Thus, 111In antimyosin uptake is a specific marker of necrotic tissue with a high signal ratio in reperfused tissue. However, its uptake is dependent on residual blood flow in the infarct territory. Indium-111 antimyosin could potentially serve as a suitable tracer for infarct sizing if myocardial blood flow in the same region were factored simultaneously.

Early Indium-111 antimyosin scintigraphy for assessment of regional wall motion asynergy on discharge after myocardial infarction

To assess the relation between early Indium-111 monoclonal antimyosin antibody scintigraphy and degree of regional asynergy on discharge, 38 patients with a first acute myocardial infarct were studied (18 anterior, 20 inferoposterior infarctions). In 21 patients thrombolytic therapy was administered. On the first day of myocardial infarction, 80 MBq Indium-111 Antimyosin was injected. Planar images, anterior, lateral and left anterior oblique, were made 24 hours later. Localized myocardial uptake was present in 37/38 patients, and was evaluated for Count Density Index (count density of infarct zone/left lung count density) in the left anterior oblique images, which displayed the infarct zone well. Regional asynergy on discharge was evaluated by cross-sectional echocardiography and defined mild (hypokinesia) or severe (akinesia or dyskinesia). Count density index was significantly lower in 15 patients with mild asynergy, compared with 22 patients with severe asynergy (1.61 +/- 0.25 vs. 2.42 +/- 0.40, p less than 0.001). This difference was present in both patient groups treated with or without thrombolysis. We conclude that early count density index, reflecting the amount of local necrosis, is highly correlated to the ultimate degree of wall motion impairment.

Frequency of myocardial indium-111 antimyosin uptake after uncomplicated coronary artery bypass grafting

The reported incidence of myocardial damage after coronary artery bypass grafting (CABG) is highly related to the methods used. Since indium-111 monoclonal antimyosin antibody scintigraphy has been shown to be highly specific and sensitive for myocardial necrosis, even in small lesions, uptake of this radiotracer was evaluated after CABG. In 23 consecutive patients without previous myocardial infarction who underwent CABG for stable angina, 80 MBq indium-111 antimyosin was injected on the third postoperative day. Planar images were obtained 48 hours later and analyzed for myocardial uptake of indium-111 antimyosin. Scintigraphic results were related to creatine kinase MB levels, duration of both aortic cross-clamping and cardiopulmonary bypass, and electrocardiographic changes. In all patients surgical procedure and postoperative course was uncomplicated. Indium-111 antimyosin uptake was present in 19 of 23 patients (82%). It was diffused in 7 patients and localized in 12. No pathologic Q waves occurred postoperatively. Fourteen patients exhibited ST-segment changes. No good relation was found among indium-111 antimyosin uptake and creatine kinase MB levels, duration of cross-clamping or bypass, and ST-T changes. It is concluded that some degree of myocardial damage, though silent, is common after CABG.

Imaging of Acute Myocardial Infarction in Pigs with Indium-111 Monoclonal Antimyosin Scintigraphy and MRI

Indium-111 antimyosin F(ab')2 was used in a series of scintigraphic studies on experimentally induced myocardial infarctions in pigs. Antimyosin distribution recorded by planar images of in vivo pigs and by single photon emission computed tomography (SPECT) of excised hearts delineated areas of myocardial necrosis if infarct volume exceeded 3.3 cm3. Scintigraphic images were compared with magnetic resonance images (MRI) obtained from excised hearts and with photographs of slices of the hearts. Infarct size and localization determined with antimyosin were compared. The MR images, with or without gadolinium-DTPA (Gd-DTPA), of the in vivo pigs were all false-negative; some myocardial wall thinning and high bloodpool signals were visible. Results show that both the antimyosin and the MR technique are specific methods for the visualization of induced myocardial necrosis in this animal model. However, the use of antimyosin is limited to a period ranging from 24 to 72 hours after infarction.

Predictive value of indium-111 antimyosin uptake for improvement of left ventricular wall motion after thrombolysis in acute myocardial infarction

In 21 patients treated with thrombolysis for acute myocardial infarction (AMI), the degree of myocardial uptake of indium-111 monoclonal antimyosin antibodies injected within 24 hours after onset of AMI was compared with the degree and extent of regional asynergy on admission and discharge, as assessed by 2-dimensional echocardiography. On the first day of AMI, 80 MBq of indium-111 antimyosin was injected and planar images were made 24 hours later. Indium-111 antimyosin uptake was evaluated for count density index (count density of infarct zone/left lung count density) in the left anterior oblique projection, in which the infarction zone was well displayed in all patients. Using 2-dimensional echocardiography, the left ventricle was divided into 13 segments and evaluated for regional asynergy, which was considered severe (akinesia or dyskinesia) or mild (hypokinesia). The extent of regional asynergy was measured by the number of asynergic segments. All 21 patients had severe regional asynergy on admission. Nine of 21 showed only mild regional asynergy on discharge and 12 of 21 had persistent severe regional asynergy in at least 1 segment. The count density index was significantly lower in patients with mild regional asynergy on discharge compared with patients with severe regional asynergy (1.63 ± 0.27 vs 2.50 ±0.42, p < 0.01). In 13 patients a decrease in the number of akinetic segments was seen between admission and discharge, whereas in 8 patients this number was unchanged; the count density index was, respectively, 1.77 ± 0.32 and 2.71 ± 0.37 (p < 0.01). It is therefore concluded that early count density index can predict wall motion improvement in the post-AMI patient treated with thrombolysis.

Patterns of evolution of myocyte damage after human heart transplantation detected by indium-111 monoclonal antimyosin

The indium-111 labeled Fab fragment of antimyosin monoclonal antibody was used to study cardiac rejection and the time course of myocyte damage after transplantation. Fifty-three studies were performed in 21 patients, 17 men and 4 women, aged 19 to 54 years (mean 37 ± 8), from 7 to 40 months after transplantation. Repeat studies were available in 8, and 10 were studied after the first year of transplantation. A heart-to-lung ratio was used for quantitation of uptake (normal 1.46 ± 0.04). Differences between absent (1.69 ± 0.29) and moderate (1.90 ± 0.36) rejection were significant (p < 0.03). Antimyosin ratio at 1 to 3 months (1.89 ± 0.35) differed from that at >12 months (1.65 ± 0.2) (p < 0.01). Repeat studies revealed a decrease in antimyosin ratio in 5 patients with uneventful clinical course; 2 had persistent activity after transplantation and suffered heart failure from rejection. After 1 year of transplantation uptake was within normal limits in 7 of 10 patients, and high uptake was associated with vascular rejection in 1. Because they can define evolving patterns of myocardial lesion activity, antimyosin studies could be useful both in patient management and in concentrating resources for those patients who most require them. The heart-to-lung ratio is suggested to monitor sequentially the degree of myocyte damage after transplantation.

Value of indium-111 monoclonal antimyosin antibody for imaging in acute myocardial infarction

In most patients with chest pain, clinical history and observed electrocardiographic and enzymatic changes are sufficient to prove or rule out an acute myocardial infarction (AMI). However, in some patients these methods fail to rule out or do not allow to localize the site of an AMI. In patients admitted several days after the acute attack of chest pain, enzyme levels may have returned to normal and the electrocardiogram may not differentiate old from recent infarction. In addition, the enzyme changes after coronary artery bypass grafting may be comparable to those seen during an AMI, but confirmation of the diagnosis and localization of the AMI on the electrocardiogram may be difficult. Localization of myocardial infarction may also be difficult in patients with a left bundle branch block or Wolff-Parkinson-White syndrome. Finally, although infarct size has been estimated by measuring enzyme levels, these values may be less reliable as a marker of infarct size after thrombolytic therapy. To overcome these problems nuclear imaging techniques have been used, particularly technetium-99m stannous pyrophosphate imaging. 1,2 However, technetium stannous pyrophosphate has disadvantages. Persistent blood pool activity and low-grade uptake in the region of the heart may be confused. In addition, uptake by overlying ribs and sternum may make interpretation of the technetium pyrophosphate scan difficult. Also, one must wait at least 24 hours, and preferably 48 to 72 hours, after the onset of chest pain. These problems may be resolved if single photon emission computed tomography and blood pool overlay techniques are used. 3 Since monoclonal antimyosin antibody labeled to indium-111 was available in our laboratory a study was undertaken to assess the value of this antibody to localize an AMI. To study the value of this technique patients were selected in whom electrocardiographic changes allowed localization of the AMI.

Indium 111-monoclonal antimyosin antibody imaging in the diagnosis of acute myocarditis.

A definitive diagnosis of myocarditis requires right ventricular biopsy. Despite its specificity, however, right ventricular biopsy may lack sensitivity due to the focal nature of the disease. Because indium 111-monoclonal antimyosin antibody imaging can be used to detect myocardial necrosis, this procedure was performed on 28 patients clinically suspected of having myocarditis, 25 of whom had left ventricular ejection fractions of less than 45%, and the results were compared with those of right ventricular biopsy performed within 48 hr of the scan. Antimyosin scans were positive in nine patients who had evidence of myocarditis on right ventricular biopsy, and negative in 11 who had no evidence of myocarditis by biopsy. The remaining eight had positive antimyosin scans but showed no evidence of myocarditis on right ventricular biopsy. On the basis of a right ventricular biopsy standard, the sensitivity of this method was 100%, the specificity 58%. We conclude that antimyosin antibody imaging is a reliable screening method for the evaluation of patients suspected of having myocarditis, and that a positive antimyosin scan indicates the need for right ventricular biopsy to establish the histologic diagnosis.

Measurement of infarct size and percentage myocardium infarcted in a dog preparation with single photon-emission computed tomography, thallium-201, and indium 111-monoclonal antimyosin Fab.

Single photon-emission tomography (SPECT) and indium 111-labeled monoclonal antimyosin Fab fragments were used to measure myocardial infarct size in 12 dogs, six subjected to balloon catheter-induced coronary artery occlusion for 6 hr (late reperfusion) and six subjected to occlusion with reperfusion at 2 hr (early reperfusion). Tomographic imaging was performed 24 hr after the intravenous injection of labeled Fab fragments with the use of a dual-head SPECT camera with medium-energy collimators. Immediately after the first tomographic scan, thallium-201 was injected into nine of 12 dogs and imaging was repeated. Estimated infarct size in grams was calculated from transaxially reconstructed, normalized, and background-corrected indium SPECT images with the use of a threshold technique for edge detection. Estimated noninfarcted myocardium in grams was calculated from obliquely reconstructed thallium SPECT images by a similar method. The animals were killed and infarct size in grams and true infarct size as a percentage of total left ventricular myocardial volume were measured by triphenyl tetrazolium chloride staining. Estimated infarct size from indium SPECT images showed an excellent correlation with true infarct size (r = .95, SEE = 4.1 g). Estimated percentage myocardium infarcted was calculated by dividing estimated infarct size from indium images by the sum of estimated infarct size plus estimated noninfarcted myocardium obtained from thallium images. Correlation between the estimated percentage of myocardium infarcted and true percentage of myocardium infarcted was excellent (r = .93, SEE = 4.4%). We conclude that dual-isotope SPECT with indium 111-monoclonal antimyosin antibodies and thallium-201 can accurately estimate infarct size and percentage myocardium infarcted.