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

September

35, 1987

Value of Iridium-111Monoclon Antimyosin Antibody for lmagin in Acute Myocardial Infarction SIMON H. BRAAT, MD CHRIS de ZWAAN, MD JACOBUS TEULE, MD GUIDO HEIDENDAL, MD HEIN J.J. WELLENS, MD

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n 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-99rn stannous pyrophosphate imaging.ls2 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 ahtibody labeled to indium-111 was available in our laboratbry 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.

THE AMERICAN

JOURNAL

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Volume 60

326

opment of new pathologic Q waves on the electrocardiogram and an enzyme rise pattern characteristic of AMI. Monoclonal antimyosin antibody was administered intravenously 24 hours after the onset of chest pain. A mouse monoclonal antibody fragment RllD10 FAb DTPA, 0.5 mg, was used labeled to 1.8 to 2 mCi of indium-111. Anterior, 45’ left anterior oblique and left lateral images were recorded 12 to 36 hours (mean 221 after injection to define the myocardial location of the tracer. All 31 patients underwent planar antimyosin imaging with a medium-sensitivity collimator with a Technicare camera 438 HR interfaced to a mobile Technicare computer 560 (pulse height analyzer set at center line of 171 and 245 keV with a 20% window). Planar antimyosin antibodies images were independently interpreted by 2 observers directly from the computer video display. Observers were blinded to the clinical data. The images were used to determine the presence or absence of tracer uptake in studied myocardial region. When uptake was present, the zone of involvement was classified as anterior or inferior using the multiple views. No patient had adverse reactions. The myocardial infarction was electrocardiographically localized in the inferior wall in 14 patients and in the anterior wall in 17. The mean peak creatine kinase level [normal value less than 240 U/liter] was 1,848 f 1,187 U/liter and mean peak serum glutamic oxaloacetic transaminase [normal value less than 40 U/liter) was 275 f 87 U/liter. Localization of the iridium-111 monoclonal antimyosin antibodies: In all 17 patients with an electrocardiographic anterior wall myocardial infarction, uptake was seen in the anterior wall of the myocardiurn [Fig. I). In 12 of the 14 patients with an electrocardiographic inferior wall myocardial infarction, uptake was seen in the inferior wall. In 1 patient no uptake was seen and ifi the another patient, with electrocardiographically an inferior wall myocardial infarction and right ventricular involvement, uptake was judged to be in the anterior wall of the myocardiurn. Imaging was repeated 24 hours after the images in 26 of the 31 patients. However, better visualization of monoclonal antimyosin antibodies labeled to indium111 was not observed in any of these patients. In 13 patients the first study showed a clearer uptake

Thirty-one patients with proved AMI were studied. Criteria for selection were precordial chest pciin typical for cardiac ischemia lasting at least 30 minutes without an adequate response to nitroglycerin, develFrom the Department of Cardiology and Nuclear Medicine, Academic Hospital of Maastricht, State University of Limburg, P.O. Box 1918, 6201 BX Maastricht, The Netherlands. Manuscript received February 3, 1987; revised mariuscript received and accepted April 13,1987.

FIGURE 1. Results of a study with monoclonal antimyosin antibody labeled to indium-111. Left, left anterior oblique projection; middle, anterior projection; right, left lateral projection of a patient with an anterior wall infarction. Apart from uptake in the sternum and liver, selective pathologic uptake is seen in the anterior wall of the myocardium.

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of indium-111, suggesting that injection of monoclonal antimyosin antibodies labeled to indium-111 approximately 24 hours after the onset of chest was preferable. Technetium pyrophosphate is proved to be a sensitive and specific agent for detecting AMI.lJ However, its disadvantages include difficulties in distinguishing between low-grade uptake, blood pool activity or overlying ribs and sternum in planar images and a required delay of at least 24 hours, and preferably 48 to 72 hours, between acute myocardial necrosis and imaging. The half-life of technetium of 6 hours can be either an advantage or disadvantage. The advantage is that a larger dose of activity can be given and that the studies can be repeated after short intervals. The disadvantage is that the interval can be too short for sufficient blood pool clearing. Monoclonal antimyosin antibodies labeled to indium-111 and especially the use of Fab result in a rapid blood pool clearance and a reduction of unwanted immunogenic reactionsa Therefore, a high target to background ratio can be achieved. No uptake of the antibodies takes place in the overlying ribs. However, antibodies labeled to indium-111 activity are present in the hepatic area, which can make the diagnosis of a small inferior wall infarction difficult or impossible. Monoclonal antimyosin antibodies labeled to indium-111 were injected 12 to 36 hours (mean 22) after the onset of chest pain and 3 planar views were recorded 24 hours later. This is possible because the half-life of indium-111 is 2.81 days. At that time minimal blood pool activity is seen. Most of the disadvantages of technetium pyrophosphate infarct imaging are therefore not present when monoclonal antimyosin antibodies labeled to indium-111 are used.

Early Precordial ST-Segment Depression Due to Isolated Acute Right or left Circumflex Coronary Artery Occlusion SYLVIA A. MAMBY, MD ARLENE B. BRADLEY, MD WILLIAM E. BODEN, MD

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rolonged chest pain (at least 30 minutes) and STsegment elevation on the admission electrocardiogram are frequently used as the sole eligibility criteria for patient enrollment into randomized studies of thromFrom the Division of Cardiology, Department of Internal Medicine, Harper Hospital/Detroit Medical Center, Wayne State University School of Medicine, 3990 John R, Detroit, Michigan 48201. Manuscript received January 30, 1987; revised manuscript received and accepted May 18,1987.

However, the high energy of indium-111 of 171 and 245 keV make use of a medium-energy collimator necessary. The high uptake in the liver can also obscure a small inferior wall myocardial infarction, as may have been the case in one of our patients. Application of single photon emission computed tomography may solve this problem.5 Infarct size must be compared between treated and untreated patients in evaluation of new thrombolytic agents. Use of enzyme levels in these studies may present problems in quantifying the infarct size. Single photon emission computed tomography of infarct imaging agents such as monoclonal antibodies labeled to indium-111 may be a better alternative. Some investigators have found that infarct size measured with monoclonal antibodies is smaller than that measured with technetium pyrophosphate, probably because indium activity is only accumulated in the necrotic area and not in the ischemic zone, while technetium uptake would take place also in the ischemic zone, but this is still controversial and needs further investigation. 1. Bruno FP, Cobb FR, Rivas F, Goodrich JK. Evaluation of ggm-technetium stannous pyrophosphate as an imaging agent in acute myocardial infarction. Circulation 1976;54:71-78. 2. Parkey RW, Bonte FJ, Meyer SL, Atkins JM, Curry GL, Stokely EM, Willerson JT. A new method for radionuclide imaging of acute myocardial infarction in humans. Circulation 1%‘4;56:546-547. 3. Corbett JR, Lewis M, Willerson JT, Nicod PH, Huxley RL, Simon T, Rude RE, Henderson E, Parkey R, Rellas JS,Buja LM, Sokolov JJ,Lewis SE. ggmTcpyrophosphate imaging in patients with acute myocardial infarction: comparison of planar imaging with single-photon tomography with an without blood pool overlay. Circulation 1984;69:1120-1128. 4. Khaw BA. Haber E. Radioimmunochemical imaeine of mvocardial infarction: utilization of anticardiac myosin antibodies. 1;: &ichikI S, Rhodes BA, Friedman B, ed. Tumor Imaging: The Radioimmunochemical Detection of Cancer. New York: Masson Publishing 1981:189. 5. Khaw BA, Gold HK, Yasuda T, Leinbach RC, Kanke M, Fallon JT, BarlaiKovach M, Strauss HW, Sheehan F, Haber E. Scintigraphic qunatification of myocardial necrosis in patients after intravenous injection of myosin-specific antibody. Circulation 1986;74:501-508.

bolytic therapy during acute myocardial infarction (AMI).lJ The rationale for using these criteria is that in most patients with acute ST-segment elevation, “transmural” AM1 and pathologic Q waves will develop if the patient is treated conventionallyP Conversely, patients presenting with AM1 characterized by electrocardiographic ST-segment depression are usually excluded from participation in acute thrombolytic trials, ostensibly because such ST-segment depression is a marker of “subendocardial ischemia” or non-Q-wave AMI, and thus is not indicative of a totally occluded infarct-related artery.4 We report 2 patients with lvessel coronary artery disease who had significant precordial ST-segment depression associated with isolated acute occlusion of a dominant right coronary artery and circumflex coronary artery, respectively. A 36-year-old man was transferred to Harper Hospital with severe substernal chest discomfort 2 to 3 hours in duration. He had no history of coronary artery disease, and his only cardiac risk factor was 2pack/day cigarette smoking. The initial blood pressure was 114/66 mm Hg, pulse 84 beats/min, lung