Assessment of myocardial necrosis by 111In-antimyosin F ab scintigraphy

111In-antimyosin F ab (AM) myocardial scintigraphy was carried out in (A) 13 patients with acute myocardial infarction (9.9 +/- 2.2 days from the onset) and (B) 9 with myocarditis and/or dilated cardiomyopathy. Forty eight hours after injection of AM, the patients were injected with 74 MBq (2 mCi) of thallium-201 (TL). The two sets of Planar and SPECT image were obtained simultaneously using dual energy window sets. In group A, positive focal AM uptake was demonstrated in 12 (92%) patients. Higher AM uptake was observed in patients who had PTCR/PTCA. By combination with TL, it is useful to detect inferior infarction and to differentiate old from acute infarction. Dual SPECT images gave precise information about the infarcted area. In group B, positive diffuse AM uptake was demonstrated in 7 (77%) patients. In conclusion, AM myocardial scintigraphy was proven to be useful for the assessment of acute necrosis after myocardial infarction but also on-going necrosis of myocarditis and/or myopathy.     

Immunoscintigraphy using 111Indium-labeled antimyosin in suspected myocarditis

111Indium-monoclonal antimyosin scans were carried out in 21 patients with suspected myocarditis, confirmed by reduced ejection volume, pericardial effusion and clinical follow up in 12 patients. Coronary heart disease was excluded angiographically in all cases. Quantitative evaluation of myocardial 111In-antimyosin accumulation 48 hours after injection showed a pathological uptake in 10/12 patients with increased heart/lung ratios (Q48 greater than 1.58). Ratios were also elevated in 2 patients with cardiomyopathy, 2 suffering from vasculitis and 1 with dermatomyositis. Four patients without proven cardiac disease had normal ratios (Q48 less than or equal to 1.58). Examination after 24 hours was of limited value, depending on the residual blood pool activity. Visual analysis of the scans showed a high interobserver variation despite a positive correlation with quantitative analysis (48 h p.i.: r = 0.72; p less than 0.001), and is not recommended. The results show the value of the 111In-antimyosin scan as a screening method prior to myocardial biopsy. However, scintigraphy cannot definitely elucidate the cause of myocardial damage. Therefore, myocardial biopsy is still recommended after positive antimyosin scans.     

Time course of myocardial infarction evaluated by indium-111-antimyosin monoclonal antibody scintigraphy: clinical implications and prognostic value.

To investigate the clinical implications of 111In-antimyosin antibody scintigraphy in the chronic stage of myocardial infarction, 34 studies were performed in 26 patients with 36 infarcts of various infarct ages. The infarcts were divided into three groups according to time from onset of chest pain to scintigraphy. Positive antimyosin images were obtained in 93% of Group I patients (3 days to 1 mo), 71% of Group II patients (1.5 mo to 1 yr) and none were obtained from Group III patients (1.5-6 yr). A negative correlation was observed between antimyosin uptake and the time after myocardial infarction. In Group II, patients with coronary artery patency and patients showing redistribution on exercise 201TI scintigraphy were more likely to have positive antimyosin images compared to patients without these features. Recurrent angina may also relate to chronic antimyosin uptake. Indium-111-antimyosin antibody scintigraphy may be a useful method in assessing the course of myocardial infarction and for the patient follow-up.     

Role of noninvasive antimyosin imaging in infants and children with clinically suspected myocarditis.

Endomyocardial biopsy is an invasive procedure, often performed on children for the diagnosis of myocarditis, and is not without risk. Therefore, a noninvasive test of adequate diagnostic accuracy is highly desirable. We evaluated the role of antimyosin scintigraphy in infants and children with clinically suspected myocarditis. METHODS: Forty patients (age range, 2 mo to 14 y) with suspected myocarditis underwent (111)In-antimyosin scintigraphy. All patients were clinically followed for 29 +/- 17 mo; 21 patients underwent serial antimyosin scans (3.8 +/- 1.7 per patient). The antimyosin uptake was assessed by heart-to-lung ratio (HLR). The scan results were compared with endomyocardial biopsy results in 22 patients. RESULTS: Thirty-five of the 40 patients showed abnormal antimyosin findings; 17 patients showed intense myocardial antimyosin uptake (HLR > 2). The HLR was higher in patients presenting within the first 2 mo of illness (2.09 +/- 0.43 vs. 1.74 +/- 0.34, P = 0.01). Of 22 patients with endomyocardial biopsy, 17 demonstrated myocarditis. All 9 patients who had an HLR > 2 and underwent endomyocardial biopsy had histologic evidence of myocarditis. Of the remaining 13 patients with HLR < 2, 8 had biopsy-verified myocarditis (62%). The intensity of antimyosin uptake was the major determinant of survival in children, with a relative risk of 18 (confidence interval, 1.34-242; P = 0.027). High antimyosin uptake (HLR > 2) seen within 2 mo of the onset of symptoms was associated with a higher mortality rate. The survivors with an HLR > 2 and those with an HLR < 2 showed a high likelihood of complete functional recovery. Furthermore, the patients with serial antimyosin scans having persistently positive findings showed a poor clinical outcome. CONCLUSION: Intense myocardial uptake of antimyosin antibody is a reliable indicator of myocarditis in infants and children. Severe myocardial damage detected in the early phase of disease is associated with a higher mortality rate. The persistence of antimyosin uptake is associated with poor clinical outcomes.     

Indium-111 antimyosin monoclonal antibody uptake in patients with cardiomyopathy and myocarditis

Prognostic significance of myocardial uptake of indium-111 antimyosin antibody was evaluated in 17 patients with idiopathic cardiomyopathy; 10 patients with dilated cardiomyopathy and 7 patients with hypertrophic cardiomyopathy. Seven of 10 patients with dilated cardiomyopathy showed positive images. Three of these 7 patients with strongly positive scans died after scintigraphic examination. Six of 7 patients with hypertrophic cardiomyopathy showed positive images. Three of the patients with dilated left ventricle had prominent positive scans and higher heart to lung ratio. The heart to lung ratio of antimyosin uptake in total patients was correlated with left ventricular end-diastolic dimension and ejection fraction measured by echocardiography. In patients with myocarditis, all three patients showed positive scintigrams within 4 weeks after the onset of the disease and 1 of 6 patients was positive thereafter, who had dilated ventricle and decreased cardiac function. Thus, indium-111 antimyosin antibody imaging may be useful to evaluate prognosis of patients with cardiomyopathy and myocarditis.     

Clinical trial of 111In-antimyosin antibody imaging: (3) Comparison with 99mTc-pyrophosphate imaging

Clinical value of 111In-antimyosin monoclonal antibody F ab (AM) was compared with 99mTc-pyrophosphate (PYP) in 13 patients with myocardial infarction and 3 patients with myocarditis. Following PYP injection, PYP imaging was performed 3 hours later. Immediately after PYP imaging, AM was administrated and AM images were obtained 48 hours later. Abnormal accumulation in the infarcted myocardium was observed in 11 patients (85%) on AM images but only in 3 patients (23%) on PYP images. All patients within 8 days after the onset of infarction showed abnormal uptake on both images. Of 5 patients with 1 to 2 weeks after the onset of infarction, abnormal uptake was observed in all of them on AM images but only in one of them on PYP imaging. Furthermore, of 6 patients with more than 2 weeks after the onset, AM imaging showed abnormal uptake in 4 (67%) but PYP imaging did not show abnormal uptake in any of them. Similarly. Of 3 patients with myocarditis, diffuse uptake in the myocardium ws observed in 2 of them on AM images but none of them showed abnormal uptake on PYP images. We conclude that AM imaging is a useful means for identifying not only acute stages but also subacute stages of myocardial necrosis where PYP imaging did not show any abnormality.     

Antimyosin uptake and myofibrillarlysis in dilated cardiomyopathy

Background

Although antimyosin scintigraphy detects myocyte necrosis associated with myocarditis, it has also been reported to yield positive results in a large number of patients with clinical dilated cardiomyopathy without histologic evidence of myocarditis. The question to be resolved is whether this discordance represents false-positive results of antimyosin scans or whether antimyosin scintigraphy more accurately identifies the presence of myocyte necrosis than does endomyocardial biopsy testing.

Methods and Results

Forty patients with the acute onset of dilated cardiomyopathy (left ventricular ejection fraction <45%; mean 27%±11%) but no endomyocardial biopsy evidence of myocarditis, were identified from a consecutive series of 50 patients who had undergone indium 111 antimyosin antibody scintigraphy and endomyocardial biopsy for suspected myocarditis. The endomyocardial biopsy specimens were analyzed to identify features correlating with antimyosin uptake or improvement in left ventricular ejection fraction (LVEF) over time. Twenty-five patients showed left ventricular myocardial uptake of radiolabeled antimyosin antibody by both planar and tomographic imaging. The remaining 15 patients had no antimyosin uptake. Of the 25, 22 (88%) patients with positive findings on antimyosin scans had degenerated, myofibrillarlytic myocytes in their biopsy specimens. Of the 15 patients with negative findings on antimyosin scans, only 6 (40%) had similar myofibrillarlytic myocytes (χ²; p<0.0047). No other histological feature correlated with the antimyosin positivity. Stepwise multiple regression analysis was performed for identification of predictors of short-term improvement in LVEF. Patients with positive findings on antimyosin scans showed a trend toward improvement with time (F=3.97; p>0.05). None of the histologic features predicted improvement in the LVEF. However, the combination of positive findings on an antimyosin scan and myofibrillarlysis did correlate significantly with spontaneous improvement in ejection fraction (F=4.53; 0.01; <p<0.05).

Conclusions

This study identifies myofibrillarlysis as a common pathologic alteration in patients with recent onset of dilated cardiomyopathy and positive findings on antimyosin scan, who lack right ventricular biopsy evidence of myocarditis. Because myofibrillarlytic cell population may represent a histologic spectrum of viable to necrotic myocytes, it appears that antimyosin uptake detects necrotic myofibrillarlytic myocytes that are not identified by light microscopy.     

Acute myocardial infarct imaging with indium-111-labeled monoclonal antimyosin Fab

Indium-111 monoclonal antimyosin Fab scintigraphy was used to detect myocardial necrosis in 52 of 54 patients (96.3%) with acute myocardial infarction. Infarcts were visualized when coronary arteries were persistently occluded (n = 10), became patent after thrombolysis (n = 33), or became patent after spontaneous reperfusion (n = 7). Posteroinferolateral visualizations were obtained in two patients with clinical and enzymatic evidence of infarction but normal electrocardiograms. Of the two patients in whom no infarcts were visualized, one had an anterior myocardial infarct. This patient underwent successful thrombolytic therapy, with attendant minimization of creatine kinase release. The other patient had a small, nonreperfused inferior myocardial infarct. Five patients with a history of remote infarction and acute necrosis showed antimyosin uptake only in regions concordant with the acute episodes of infarction, and radiolabeled antimyosin Fab localized in neither old infarcts nor normal, noninfarcted myocardium. Antimyosin Fab scintigraphy, thus, appears to be a highly specific means of delineating necrotic myocardium, at least in this limited and selected group of patients.     

Indium-111-antimyosin images compared with triphenyl tetrazolium chloride staining in a patient six days after myocardial infarction.

The results of indium-111 (111In) antimyosin imaging during life and the findings on postmortem imaging and triphenyl tetrazolium chloride (TTC) staining of the heart are reported from a patient who received 111In-antimyosin on the sixth day following myocardial infarction and died after imaging the next day. The planar images obtained during life showed abnormal 111In-antimyosin uptake in the posterior, lateral, and apical walls of the left ventricle. Autopsy revealed extensive infarction of the left ventricular lateral and posterior walls with cardiac rupture, which was the cause of sudden death. Direct imaging of the sliced specimen of heart revealed abnormal tracer uptake in the lateral and posterior walls of the left ventricle, which correlated closely with the area of necrosis outlined by TTC staining. Our results confirm the experimental findings that antimyosin antibody binds specifically to the acute irreversibly damaged myocardial cells. A high degree of tracer uptake can be seen even when 111In-antimyosin is injected six days postinfarction.     

Clinical role of indium-111 antimyosin imaging.

Myocyte necrosis occurs in ischaemic, inflammatory and toxic heart diseases and can be detected by indium-111 antimyosin imaging. This allows a non-invasive evaluation of the site, extent and quantitation of the severity of myocardial necrosis. Simultaneous imaging of perfusion in patients with myocardial infarction allows the differentiation of necrosed and perfused areas and the varying degrees of mismatch and overlap, which has prognostic significance. 111In-antimyosin imaging is useful in the assessment of patients with unstable angina and in those for whom the diagnosis of infarction or unstable angina is not clear. In suspected myocarditis, a positive scan indicates the necessity for endomyocardial biopsy to confirm inflammation, whereas a negative scan makes the diagnosis of myocarditis unlikely. Antimyosin imaging is not useful as a marker of rejection in the 1 year post-transplant, but uptake after this period is associated with an increased rejection rate and is therefore an important tool in planning management strategies. Most patients on anthracycline treatment have demonstrable uptake, which is related to the cumulative dose and to the ejection fraction. Its role in this situation is as yet unclear. The use of new ligands and radioisotopes (99mTc) is likely to allow earlier imaging and produce improved quality.     

Clinical role of indium-111 antimyosin imaging

Myocyte necrosis occurs in ischaemic, inflammatory and toxic heart diseases and can be detected by indium-111 antimyosin imaging. This allows a non-invasive evaluation of the site, extent and quantitation of the severity of myocardial necrosis. Simultaneous imaging of perfusion in patients with myocardial infarction allows the differentiation of necrosed and perfused areas and the varying degrees of mismatch and overlap, which has prognostic significance.¹¹¹In-antimyosin imaging is useful in the assessment of patients with unstable angina and in those for whom the diagnosis of infarction or unstable angina is not clear. In suspected myocarditis, a positive scan indicates the necessity for endomyocardial biopsy to confirm inflammation, whereas a negative scan makes the diagnosis of myocarditis unlikely. Anti-myosin imaging is not useful as a marker of rejection in the 1 year post-transplant, but uptake after this period is associated with an increased rejection rate and is therefore an important tool in planning management strategies. Most patients on anthracycline treatment have demonstrable uptake, which is related to the cumulative dose and to the ejection fraction. Its role in this situation is as yet unclear. The use of new ligands and radioisotopes (^99mTc) is likely to allow earlier imaging and produce improved quality.     

111In-antimyosin Fab scintigraphy in cardiovascular diseases: (multicenter clinical trial)

In a multicenter study, a total of 380 patients with myocardial infarction, myocarditis and cardiomyopathy underwent 111In-Antimyosin Fab myocardial imaging. 111In-Antimyosin Fab was administered intravenously and myocardial images were obtained 48 hours later. Only 3 patients developed mild adverse effects. Human antimouse antibodies were detected in 7 patients. Positive scans in patients with myocardial infarction were seen in 92/119 (77%) within 2 weeks after the onset of myocardial infarction, in 58/71 (82%) at 3-4 weeks, in 20/22 (91%) at 4-8 weeks and 17/31 (55%) thereafter. The location of myocardial damage delineated by 111In-Antimyosin Fab imaging was concordant with the infarct location by ECG and coronary angiography. In patients with myocarditis, 111In-Antimyosin Fab uptake was positive in 7/12 (58%) within 8 weeks and 6/17 (35%) thereafter. Positive 111In-Antimyosin Fab scans were seen in 12/36 (33%) in dilated cardiomyopathy and in 17/19 (89%) in hypertrophic cardiomyopathy. Although the mechanism of persistently positive 111In-Antimyosin Fab images in the subacute to chronic stage of myocardial infarction and myocarditis remains to be clarified, 111In-Antimyosin Fab may be useful for the detection of the diseases and in evaluating the prognosis of patients with cardiomyopathy.     

Clinical application of Indium-111 antimyosin antibody and Thallium-201 dual nuclide single photon emission computed tomography in acute myocardial infarction

The significance of indium-111 antimyosin antibody and thallium-201 dual nuclide single photon emission computed tomography (SPECT) was evaluated in 7 patients with acute myocardial infarction (AMI) who underwent emergency coronary angiography with successful revascularization by intracoronary thrombolysis. Indium-111 antimyosin antibody and thallium-201 dual nuclide SPECT was performed 11 to 36 days after the onset of AMI. Antimyosin SPECT images delineated areas of myocardial necrosis in all 7 patients (100%), but planar images detected necrotic areas in only 4 of 7 patients (57%). Peak CPK-MBs of the 3 patients in which no necrotic area was detected by indium-111 planar image showed a tendency to be smaller. Indium-111 antimyosin antibody/thallium-201 overlap was observed in all patients. The area of overlap was at the center of necrosis in 4 patients (2 anterior infarction, 1 inferior infarction, 1 inferolateral infarction) and at the peripheral portion in 3 patients (all 3 had inferior infarction). Indium-111 antimyosin antibody and thallium-201 dual nuclide SPECT is useful in identifying the localization of myocardial infarction and the overlap of these tracers might reflect the presence of salvaged myocardium adjacent to the necrotic myocardium.     

Indium-111-antimyosin antibody imaging for detecting different stages of myocardial infarction: comparison with technetium-99m-pyrophosphate imaging

The diagnostic value of 111In-antimyosin (AM) imaging for identifying myocardial infarction was evaluated in comparison with 99mTc-pyrophosphate (PPi) imaging. Twenty-four patients with various stages of myocardial infarction, ranging from three days to nine months after the onset of infarction, underwent both AM and PPi scans. Of 26 infarct lesions AM scan identified 22 (85%), while PPi scans detected 10 (38%) (p less than 0.01). When less than a week had passed since the onset both scans demonstrated all infarct lesions. For seven subacute lesions studied within one to two weeks of onset, AM scans detected (100%), while PPi scans identified only 2 (29%). Furthermore, AM scans showed discrete myocardial uptake in 7 (64%) of those studied more than two weeks after onset. The intensity of AM uptake in the infarcts studied more than seven days after onset was less than that in acute infarcts studied within seven days of onset (p less than 0.05). These preliminary data indicate that the abnormal myocardial uptake of AM persists beyond the first two weeks when PPi no longer accumulates. Thus, AM scans can be considered to provide a sensitive diagnosis of subacute as well as acute myocardial necrosis.     

Immunoscintigraphy with 111In antimyosin Fab

Monoclonal 111In antimyosin Fab is a marker for myocytes which have lost their membrane integrity. Because of the slow blood pool clearance of the radiopharmaceutical, imaging is usually started 24-48 h after intravenous injection of 74 MBq of the tracer. This long postinjection interval restricts its utilization in the primary diagnosis of acute myocardial infarction. However, antimyosin may help to differentiate between necrotic and viable myocardium in the subacute stage of incomplete myocardial infarction. Serial endomyocardial biopsy for early detection of transplant rejection after heart transplantation may be partially replaced or supplemented by antimyosin scintigraphy. The compound may facilitate the diagnosis of myocarditis. Other potential indications may be prognostic assessment of dilated cardiomyopathy, monitoring cardiotoxic side-effects of chemotherapeutics, recognition of cardiac contusion as well as diagnosis of rhabdo- and leiomyosarcoma. In specific clinical situations 111In antimyosin Fab immunoscintigraphy may provide valuable diagnostic information.     

Visualization of myocardial infarction 6 h after injection of 111In-antimyosin antibodies using a blood pool subtraction technique.

111In-antimyosin antibodies are capable of visualizing myocardial infarction (MI). Because of slow blood clearance, images are usually recorded 24 or 48 h postinjection. In this pilot study, a blood pool subtraction technique, which makes it possible to visualize MI 6 h postinjection, is validated. Twenty-five patients with proven MI (16 anterior, 9 inferior) were imaged a few minutes, 6 and 24 h after an injection of 111 MBq 111In-labelled antimyosin antibodies. Three planar views are obtained each time. Using software which performs the geometric registration, the grey level normalization and the subtraction of images, the blood pool image (obtained a few minutes postinjection) is subtracted from the 6 h image. The resulting image is the blood pool corrected 6 h image. The 24 h images and the blood pool corrected 6 h images were interpreted blindly and the number of correct, incorrect and impossible MI localizations was counted. The number of correct localizations is 19/25 for the standard 24 h images and 22/25 for the blood pool corrected 6 h images. Then, with this blood pool subtraction method, it is possible to visualize MI 6 h postinjection. This has to be taken into account when discussing the role of antimyosin scintigraphy in the management of patients with MI.     

Accumulation of 111In-antimyosin antibody at the focal site of inflammation

An p6-year-old man with anterior acute myocardial infarction was administered antimyosin antibody labeled with 74 MBq (2 mCi) 111In, and abnormal hot activity was observed in the left lung by immunoscintigraphy. 67Ga-citrate scintigraphy also showed abnormal uptake in this lesion. At this time, this patient complained of fever and cough with sputum, and roentgenography showed a coin lesion-like shadow at the same location of the lung. By treatment with antibiotics, his symptom was improved and coin lesion-like shadow disappeared. So we thought the RI uptake area in the left lung was inflammatory lesion. This case suggests that 111In-antimyosin antibody can be trapped to the focal site of inflammation.     

Lyme myocarditis diagnosed by indium-111-antimyosin antibody scintigraphy

We report a new case of Lyme disease with cardiac manifestations, which has been possible to follow during the long period of 12 years. We have detected the usual ECG abnormalities, and concentric hypertrophic myocardiopathy, by echocardiography. The acute myocarditis was demonstrated by 111In-antimyosin scintigraphy, which showed global myocardial uptake of the tracer, constituting the first report, to our knowledge, of Lyme myocarditis diagnosed by this method.     

Imaging of cardiac transplantation rejection in primates using two new antimyosin agents.

Indium-111-labeled monoclonal antimyosin Fab has been used to image myocardial infarction, myocarditis and cardiac transplant rejection with localization in myocytes that have suffered irreversible loss of cell membrane integrity. Technical factors potentially limiting clinical usefulness of 111In antimyosin include dosimetry (72 hr half-life of 111In), slow blood clearance of antibody proteins delaying optimal imaging to 24 to 48 hr postinjection and nontarget organ uptake. Therefore, two new antimyosin imaging agents experimentally shown to potentially improve dosimetry, shorten time from injection to imaging or decrease nonspecific cell binding were evaluated in a primate cardiac transplant model. The two agents evaluated were polylysine 111In-antimyosin (0.023 mg Fab modified with a 3.3 kd polymer of polylysine and labeled with 111In) and 99mTc-antimyosin (0.5 mg Fab' antimyosin labeled using the RP-1 ligand technique). A total of eight baboons were studied: three with heterotopic (cervical) xenographs, three with orthotopic allographs and two control animals. Each animal was injected first with 12-23 mCi of 99mTc-RP-1 antimyosin and 5-16 hr after completion of imaging, was injected with 0.72-1.88 mCi of 111In-polylysine antimyosin (PIs) and reimaged 12-48 hr later. The imaging results were compared to the histology of the animals. Biexponential curves were fit to the blood sample data and rate constants were determined and expressed as T1/2 values. There were no significant differences between the two agents in either the early fast components or the late slow components. On planar imaging, there was blood-pool activity at 10-12 hr postinjection of both agents, but by 16-24 hr postinjection, blood pool was negligible on the 111In-PIs scans. Both agents were concentrated in the rejected cardiac tissue. The slow blood-pool clearance combined with the 6 hr half-life of 99mTc-RP-1 AMA make this agent less promising for detection of diffuse myocardial uptake than 111In Fab modified with polylysine.     

Lyme myocarditis diagnosed by indium-111-antimyosin antibody scintigraphy

We report a new case of Lyme disease with cardiac manifestations, which has been possible to follow during the long period of 12 years. We have detected the usual ECG abnormalities, and concentric hypertrophic myocardiopathy, by echocardiography. The acute myocarditis was demonstrated by ¹¹¹In-antimyosin scintigraphy, which showed global myocardial uptake of the tracer, constituting the first report, to our knowledge, of Lyme myocarditis diagnosed by this method.