Clinical trial of 111In-antimyosin antibody imaging: (2). Imaging of myocardial infarction and myocarditis

A new scintigraphic method to detect myocardial necrosis has been developed using antimyosin monoclonal antibody F ab labeled with indium-111 (111In-antimyosin). We investigated 111In-antimyosin scintigraphy in 35 patients with myocardial infarction, 5 patients with myocarditis and 3 patients with angina pectoris. 111In-antimyosin F ab was administered iv and antimyosin images were recorded by planar and single photon emission computed tomography (SPECT) 48-72 hrs after injection. Planar images showed discrete localization of 111In-antimyosin in 26 of 27 patients within 16 days after the onset of acute myocardial infarction in 14 of whom creatine kinase, glutamic oxaloacetic transaminase and lactic dehydrogenase had already normalized. In addition, positive scans were also obtained in 4 of 8 patients 1 to 9 months after the onset of the disease. Three patients with acute myocarditis (two of whom were biopsy-proven) had positive scans 2 and 4 weeks after the onset of the disease. Although mechanism of persistent positive anti-myosin images in the chronic stage remains to be clarified, 111In-antimyosin scintigraphy holds potential promise as a noninvasive method for the detection of myocardial injury.     

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.     

In-111 antimyosin-Fab uptake in contractile myocardium of old myocardial infarction]

As In-111 monoclonal antimyosin antibody (AM) has been thought to bind with human myosin exposed in myocytes irreversibly damaged by an ischemic event. The AM uptake in contractile myocardium after acute myocardial infarction was studied. AM planar images were obtained 48 hours later after injection of 74 MBq of AM in 6 patients 2-10 months later after acute myocardial infarction. Mean ejection fraction was 66% (75-58). Myocardial AM uptake was definite in comparison with mediastinum uptake in all 6 patients and mean heart lung ratio was 2.3 +/- 0.5. AM SPECT images and T1-201 SPECT images were obtained with dual mode. Mean T1-201 uptake at the region of maximal AM uptake was 77% (90-63). Echocardiography showed contractility of the region. Mean maximal AM uptake in the anterior wall region was 83% (100-75) and mean T1-201 uptake at the region was 81% (90-75) and shortening rate of the region was 34% (52-25). The region with AM uptake has been shown to correlate with the region salvaged from necrosis by reperfusion. It has been shown that AM was uptaken in contractile myocardium in chronic phase of acute myocardial infarction. It was suspected that myocardium under severe ischemic event may be salvaged by reperfusion therapy and retain contractility in chronic phase, however irreversible damage, which permit AM uptake, may remain in myocardium.     

Diagnostic utility of 111In-antimyosin Fab scintigraphy in acute myocardial infarction: comparison with 201Tl and 99mTc-pyrophosphate myocardial scintigraphy]

To assess the diagnostic accuracy, extent, and characteristics of 111In-antimyosin Fab scintigraphy (In-AM) in acute myocardial infarction (AMI), we studied In-AM in 17 patients with AMI and compared with In-AM, 99mTc-PYP and 201Tl scintigraphy. Intensity of In-AM uptake was classified into 3 grades. Fourteen of 17 patients (82%) showed positive uptake of In-AM. The locations of infarct area diagnosed by In-AM were in accordance with those by electrocardiography. There was a good correlation between the extent score of In-AM planar and that of SPECT (r = 0.72), In-AM SPECT and Tl SPECT (r = 0.79), In-AM planar and PYP planar (r = 0.92), In-AM SPECT and PYP SPECT (r = 0.76), respectively (p less than 0.01). Thus, In-AM is a useful method for diagnosis of AMI.     

Feasibility of long-term outcome prediction in acute myocardial infarction using the discordance between early and delayed image on 123I-BMIPP myocardial scintigraphy

OBJECTIVES: The feasibility of long-term outcome prediction using BMIPP myocardial scintigraphy was evaluated in cases of acute myocardial infarction. METHODS: BMIPP myocardial scintigraphy was performed on 165 patients with first acute myocardial infarction at the time of discharge from the hospital (average of 27 days after disease on set). Discordance between early and delayed image was checked and its relation to later cardiac events (during the mean follow up period of 64.2 +/- 9.8 months) was analyzed. In 82 of these 165 cases TlCl scintigraphy was simultaneously performed (Tl/BMIPP dual SPECT) to examine mismatch form BMIPP scintigraphy and discordance between early and images. RESULTS: Discordance between early and delayed images was observed in 86 cases (52%). Among patients for whom dual SPECT was performed, mismatch between TlCl and BMIPP scintigraphy was observed in 30 cases (37%). When the relation between mismatch and discordance was analyzed, mismatch was accompanied by washout. The incidence of later cardiac events was significantly higher for cases showing discordance accompanied by washout and cases showing mismatch on dual SPECT scintigraphy than cases without these findings. When multivariate analysis was conducted, involving age, sex, infarction related artery, left ventricular end-diastolic volume index, left ventricular ejection fraction, severity of disturbed fatty acid metabolism, washout and fill-in, washout was identified as an independent predictor of cardiac events. CONCLUSION: Mismatch on Tl/BMIPP dual SPECT is important for predicting long-term prognosis of acute myocardial infarction. Furthermore, washout on BMIPP scintigraphy is also useful as a predictor of cardiac events.     

Myocardial imaging in acute myocardial infarction using beta-methyl-p-(123I)-iodophenylpentadecanoic acid: comparison with 201Tl imaging and wall motion]

Myocardial imaging using beta-methyl-p-(123I)-iodophenylpentadecanoic acid (BMIPP) was performed in 11 patients with acute myocardial infarction. The left ventricular images were divided into 12 segments, and myocardial imagings with BMIPP were compared with coronary angiography (CAG), thallium-201 myocardial scintigraphy (TL) and wall motion obtained by two-dimensional echocardiography (WM). When the culprit lesion was at the proximal point of the left anterior descending artery (LAD), all segments showed depressed uptake. In 3 cases with single vessel disease of the LAD, inferior wall of the basis showed reduced uptake of BMIPP despite the location of the culprit lesion. In cases with discordant uptake between the two tracers, BMIPP frequently showed more severely depressed uptake than TL in the subacute phase, although the uptake of BMIPP correlated with that of TL (tau = 0.82, p less than 0.001). In such cases, the discordance was related to the improvement in WM from the acute phase to the convalescent phase. BMIPP uptake correlated with WM in the subacute phase (tau = 0.50, p less than 0.001). BMIPP showed more severely depressed uptake while WM showed mild asynergy in most cases in which discordance was found between the BMIPP and WM findings. However, there was no correlation between the change in WM from the acute to subacute phases, or the uptakes of BMIPP and TL alone. We concluded that the myocardial condition can be evaluated in detail in acute myocardial infarction by comparing the findings of BMIPP with those of TL and WM.     

A case of rhabdomyolysis demonstrated by Tc-99m methylene diphosphate scintigraphy

Technetium-99m phosphate compounds are useful for bone scintigraphy. Furthermore they occasionally demonstrated acute myocardial infarction and myocarditis as positive lesions. Also accumulations in the extraskeletal muscle have been reported using these compounds. This case was a 47-year-old male and had localized rhabdomyolysis, caused by compartment syndrome. We report the usefulness of technetium-99m methylene diphosphonate to diagnose the location of rhabdomyolysis.     

Clinical usefulness of 201Tl/99mTc-PYP dual myocardial quantitative gated SPECT program using low-dose dobutamine loading in assessment of myocardial viability in patient with acute myocardial infarction--a case report

An 86-year-old man with chest pain was admitted to our hospital. Coronary angiography revealed 99% stenosis of the mid segment of the left anterior descending coronary artery, therefore, a coronary stent was implanted. Immediately after the stent implantation, 99% stenosis occurred at the proximal site of the 1st diagonal artery because of stent jeal. On the 4th hospital day, ECG-gated 201TL/99mTc-PYP dual myocardial quantitative gated SPECT was performed at rest and during low-dose dobutamine loading. The 201Tl scintigraphy revealed moderately reduced uptake in the anterior, septal and apical walls, and 99mTc-PYP uptake was observed in the mid-anterior wall. A three-dimensional surface display of gated 201Tl SPECT images showed severe hypokinesis in the anterior, septal and apical walls at rest. On the other hand, during low-dose dobutamine loading, improved wall motion was observed in the basal anterior and septal walls, while no change was observed in the midanterior and apical wall movements. Three-dimensional surface display of gated 201Tl/99mTc-PYP dual SPECT images revealed similar patterns of wall motion as those of gated 201Tl SPECT images at rest. During low-dose dobutamine loading, on the other hand, a three-dimensional surface display of gated 201Tl/99mTc-PYP dual SPECT images revealed improved wall motion in the basal anterior, septal and apical walls, but worsened wall motion of the mid-anterior wall. After 6 months, a follow-up coronary angiography revealed no re-stenosis of the stent, but 99% stenosis at the proximal aspect of the 1st diagonal artery. Left ventriculography revealed improved wall motion in the apex and akinesis of the mid-anterior wall. These wall motion findings were similar to those visualized in the three-dimensional surface display of gated 201Tl/99mTc-PYP dual SPECT images during low-dose dobutamine loading in the acute phase. These results suggest that 201Tl/99mTc-PYP dual myocardial quantitative gated SPECT using low-dose dobutamine loading could be useful for the assessment of myocardial viability after reperfusion therapy in patients with acute myocardial infarction.     

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.     

New color imaging of [99mTc]-pyrophosphate and [201Tl]-chloride dual isotope single photon emission computed tomography in acute myocarditis

[99mTc]-pyrophosphate (PYP) and [201Tl]-chloride dual isotope single photon emission computed tomography (SPECT) is now available to detect the site and extent of acute myocardial infarction. In inflammatory myocardial disease, [99mTc]PYP makes hot image on damaged area. We performed dual isotope SPECT of [99mTc]PYP and [201Tl]Cl in two patients with acute myocarditis and severe rhythm disturbance to evaluate the severity of inflammation. Myocardial damage was estimated by [201Tl] perfusion coloring blue and myocardial inflammation was estimated by [99mTc]PYP uptake coloring red. The overlap display of both images made it clear to detect spatial extent of myocardial inflammation. Using this technique, we expect to estimate the severity of myocarditis and to make a decision of therapeutic plan.     

Acute myocarditis presenting as acute myocardial infarction and sudden death with complete atrioventricular block: Value of antimyosin scintigraphy

Conclusion  Because endomyocardial biopsy may have poor sensitivity in clinical practice, antimyosin scintigraphy can be an effective noninvasive tool for diagnosing diffuse myocyte necrosis in acute myocarditis. In case of acute AV block, the diagnosis of myocarditis is clinically relevant because permanent pacing is not usually required, and the differential diagnosis with acute myocardial infarction may be difficult. Antimyosin scintigraphy may thus have therapeutic implications in acute AV block.     

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.     

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.     

Myocardial viability in QS region after PTCR

Myocardial viability after PTCR in patients with first anterior myocardial infarction was studied one month after the onset of acute myocardial infarction by profile curve of Tl-201 coronal myocardial SPECT images. Patients were devided into two groups according to left ventricular ejection fraction (EF), i.e. group A (EF more than 50%; 11 cases , EF; 62 +/- 10%) and group B (EF less than 50%; 9 cases, EF; 40 7%). Patients in group A showed an increase in serum GOT at the acute phase of acute myocardial infarction (322 +/- 182IU), decreased %Tl-201 uptake in QS region (65 +/- 7%) significantly less than the normal range, large size of region of infarction (214 +/- 83 degree) and abnormal QS in ECG (V1-3QS; 2 cases, V1-4QS; 8 cases, V1-5QS; 1 case). Improvement of wall motion in region of infarction was noted in 9 cases. Patients in group B showed an increase in serum GOT (651 +/- 382 IU p; ns), %Tl-201 uptake in QS region (48 +/- 7% p greater than 0.001) significantly less than the %Tl-201 uptake in group A, size of defects (243 +/- 45 p; ns) and abnormal QS in ECG (V1-3QS; 1 case, V1-4QS; 7 cases V1-5QS; 1 case). Improvement of wall motion was noted in 2 cases. The study showed that %Tl-201 uptake in region of infarction in patients with well EF was significantly more than that in patients with depressed EF. Mechanism of maintaining well EF after PTCR was suggested as the following, i.e. in the region released from severe ischemic attack part of myocardium resulted in necrosis, accompanying elevation of serum enzyme and appearance of QS, though part of myocardium might be salvaged from necrosis and contribute to EF in chronic phase. It has been generally thought that abnormal QS waves noted in anterior chest leads of ECG in chronic phase indicated transmural myocardial infarction in the anterior region. From this study it was concluded that QS region with %Tl-201 more than 50% did not generally correspond to transmural myocardial necrosis and that for estimation of myocardial viability %Tl-201 uptake might be more useful than ECG.     

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.     

Serial change of TL/BMIPP dual SPECT myocardial scintigram in patients with acute myocardial infarction; meaning of chronic mismatch phenomenon]

This study was aimed to elucidate the serial changes and clinical significance of accumulation mismatch with TL and BMIPP dual SPECT myocardial scintigraphy during 6 months in patients with acute myocardial infarction (AMI). The dual SPECT scintigraphy was performed at one, three and six months after onset of AMI in 46 patients who underwent reperfusion therapy. Long axis fractional shortening in infarct-related area and left ventricular end-diastolic volume index (LVEDVI) were measured by left ventriculography performed immediately after reperfusion and at one, six months after onset of AMI. The patients were divided into two groups: those with mismatch (Group (+)) and those without (Group (-)) at one month after reperfusion. Group (+) was subdivided into three groups according to duration of persistence of mismatch; one month persistence (1 M), three months (3 M) and six months (6 M). Improvement of wall motion abnormality (WMA) in infarct-related area was seen at one month after reperfusion in group 1 M and group 3 M, while group 6 M showed no apparent change in WMA throughout the study period. LVEDI did not change at six months after reperfusion in group 1 M and 3 M, while significant increase was seen in group 6 M. It is concluded that the case with disappearance of mismatch between TL and BMIPP until three months after reperfusion indicates myocardial stunning while in the case with long-standing mismatch left ventricular remodeling is suggested.     

Utility of rest Tl-201 myocardial SPECT images for estimating myocardial viability]

Rest Tl-201 myocardial SPECT images were underwent in 19 patients with anterior wall myocardial infarction under PTCR one month after the onset of acute myocardial infarction. The relationship between shortening rate (SR) of the left ventricle estimated by radial method and corresponding %Tl-201 uptake obtained by circumferential profile analysis was studied. For each patients 10 points on the anterior wall were taken into consideration. Seven patients showed depressive flat profile curve and 12 patients showed slant curve, in which %Tl-201 uptake continuously decreased from base to apex. Well correlation was obtained between SR and %Tl-201 uptake (SR = -41.2 +/- 1.03% Tl-201 uptake, r = 0.54, p less than 0.001). Average %Tl-201 uptake corresponding to SR = 0 was 46.3 + 6.8% (36-58). The sensitivity of %Tl-201 uptake greater than or equal to 60% for SR greater than or equal to 20% was 97% (87/90) and specificity was 69% (31/45). Tl-201 myocardial SPECT images were useful for estimating myocardial viability and %Tl-201 uptake was one of excellent parameters for quantitatively estimating myocardial viability.     

Assessment of myocardial damage in cardiomyopathy using 111In-antimyosin Fab myocardial scintigraphy

111In-antimyosin Fab (AM) myocardial scintigraphy was carried out in (A) 10 patients with idiopathic dilated cardiomyopathy, (B) 7 with dilated phase of hypertrophic cardiomyopathy and (C) 8 with normal (control) individuals. Imaging was taken 48 hours after intravenous injection of 74 MBq of AM. Myocardial uptake of AM was evaluated qualitatively and quantitatively. Positive uptake was observed in 9/10 (90%), 7/7 (100%) and 0/8 (0%) in group A, B and C, respectively. AM index (heart/lung ratio) in group A and B were 2.04 +/- 0.24 and 2.46 +/- 0.49, values significantly higher than that obtained in the control patient without cardiomyopathy (1.51 +/- 0.13) (p less than 0.01). Positive monoclonal antimyosin antibody studies were highly prevalent in dilated cardiomyopathic and dilated phase of hypertrophic cardiomyopathic patients, even in the presence of negative right ventricular biopsy. It is suggested that this method was useful for the noninvasive assessment of active myocardial damage in these patients.     

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.     

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.