jnm/DIAGNDBTIC NUCLEAR MEDICINE

LOCALIZATION OF MYOCARDIAL DISORDERS OTHER THAN INFARCTION WITH 99mTCLABELED PHOSPHATE AGENTS

LouisA. Perez, David B. Hayt, and Leonard M. Freeman Misericordia Hospital Medical Center and the Albert Einstein College of Medicine, Yeshiva University, Bronx, New York

Myocardial studies with 99mTc@labeled phos tion of tracer to the myocardium (4) . In another phate agents were obtained in 20 patients with study, Willerson et al reported on 202 patients ad out demonstrable cardiovascular disease, 24 mitted to their coronary care unit with chest pain patients with unstable arteriosclerotic heart dig of varying origins (5) . Of these, 101 did not develop ease (ASHD) without acute infarction, and six clinical or electrocardiographic evidence of acute patients with myocardiopathy. The patients myocardial infarction and 92 had negative myocar without cardiovascular disease showed no locali dial scintigrams. Seven of the remaining nine patients zation of tracer; the patients with unstable ASHD had “unstableangina pectoris―and a faint, but defi and without acute infarction showed nonfocal nitely positive myocardial scintigram (5) . The pres ill-defined accumulation of tracer; and the pa ent investigation was undertaken to assess the pos tients with myocardiopathy showed diffuse ac sible cardiac uptake of radiophosphate in patients cumulation of tracer throughout the confines with no demonstrable cardiac disease, with arterio of an enlarged cardiac outline. Careful evalua sclerotic heart disease, and with myocardiopathy. tion of both the distribution and intensity of the activity, in conjunction with the clinical pic MATERIALS AND METHODS ture, allows differentiation among these disease Fifteen millicuries of either eemTc_stannous poly processes. Since ischemic areas around infarcted phosphate (New England Nuclear Corp., North Bit tissue may show increased activity, the value of lerica, Mass.) or oemTc@pyrophosphate (TechneScan this technique for sizing acute myocardial in PYP Kit, Mallinckrodt/Nuclear, St. Louis, Mo.) farction may be limited. was administered intravenously to each patient. The tracer was prepared according to the manufacturer's

Bonte reported that eemTc@stannouspyrophosphate localizes in dog myocardium after experimentally Received May 24, 1975; revision accepted Oct. 22, 1975. For reprints contact: Louis A. Perez, Dept. of Nuclear produced myocardial infarction (1 ) . Investigations Medicine, Norwalk Hospital, 24 Stevens St., Norwalk, Conn. in humans showed positive myocardial images in 15 06856. patients with acute transmural myocardial infarction (2) . Of these patients 13 gave positive studies 3—7 days after the initial episode. Electrocardiograms (ECG) correlated well with the localization of the infarct. Two patients with arteriosclerotic heart dis ease (ASHD) showed questionably increased ac tivity in the region of the left ventricle (2) . Acute subendocardial infarction has also been documented with this technique (3). Willerson et al have re ported that of 55 patients admitted for chest pain who did not evolve ECG or enzyme evidence of FIG. 1. Normalheart(Group1).Radioactivityis notincreased myocardial infarction, none showed positive localiza in vicinity of heart.

Volume 17, Number 4 241 PEREZ, HAYT, AND FREEMAN instructions and used within 3 hr of preparation. At era peak set at 140 keV with a 20% window. The 90 mm and again at 4 hr after injection, left an- records were obtained with Polaroid and 35-mm film. tenor, left anterior oblique, and left lateral scinti- Informed consent was obtained from all patients. grams of the upper thorax were obtained. Using a They were divided into three groups: Searle Radiographics Pho/Gamma III HP scintilla- Group 1. Patients without evidence of cardio tion camera, a high-resolution 140-keV collimator vascular disease. was centered at the point of maximal cardiac pulsa- Group 2. Patients with arteriosclerotic heart tion for each view. Three hundred thousand counts disease without acute infarction. were accumulated for each scintigram with the cam- Group 3. Patients with myocardiopathy.

NOACUTEINFARCTIONPaTABLE 1.PATIENTSWITh ARTERIOSCLEROTICHEARTDISEASEAND

between anginol episode tlent and imaging est ut est No.AgeSexIntervalLDHScintigram177F7tSR (days)Dischargediagnosis ECG findingsHigh SGOTHigh CPKHigh

ASHD with cardiomegaly. with frequent APCs2155205 Mild increased activity at inferior CAstomach,S/P subtotal aspect of left ventricle gastredtomy 2 62 M 2 ASHD—unstableangina Old anterior wall myocardiol 30 55 305 Mild increased activity at apex infarct-—ag. indeterminate of left ventricle 3 66 M 6 ASHD with cardiomegaly. Nonspecific ST & T wave 30 70 360 Mild increased activity at in CAlung.S/P right changes. Old anteroseptal ferior aspect of left ventricle upper lobectomy infarct. Atrial fibrillation with rare ectopic beats 4 36 M 2 Acute pulmonary thrombo NonspecificST & T wave 15 75 220 Moderate increased ill-defined emboli changes activity at anterior left yen tricle S 51 F 7 Hypercholesterolemia NonspecifIc ST & T wave 36 120 350 Mild increased activity at apex changes of left ventricle 6 56 M 2 ASHD, diabetes Nonspecific ST& T wave 22 55 250 Moderate increased activity at changes inferior surface of left ven tricle 7 50 F 3 ASHD with cardiomegaly. Old inferior wall myocordial 38 110 330 ModerateIncreasedactivityat hypertension infarct—ageindeterminate medial border of left ventricle 8 72 F 3 ASHDwithunstableangina Old inferior wall myocardial 20 60 200 Mild increasedactivityat infarct—age indeterminate medial border of left ventri dc 9 65 F 8 ASHD with cardiomegaly. Left ventricular hypertrophy 80 40 280 Mild increased activity through. CAcervix out left ventricular contour 10 87 M 2 ASHD with unstable an Nonspecific ST & T wave 33 60 185 Mildincreasedactivitythrough gina, CA prostate changes. intraventricular out left ventricular contour conduction defect 11 42 F 8 CAbreast,S/P radical NonspecificST & I wave 24 205 350 Moderate increased activity at mastectomy.diabetes, changes apex of left ventricle hypercholesterolemia, hypothyroidism 12 60 M 3 ASHD with unstable an Old anteroseptal myocardial 23 1t5 390 Moderate increased activity at gina, cardiomegaly infarct—ageindeterminate anterior left ventricle 13 83 M 10 CA prostate NonspecificST & T wave 20 60 200 Mild increased activity at in changes ferior surface of left ventricle 14 75 F 3 ASHD with unstable angina Nonspecific ST & T wave 34 60 350 Mildincreasedactivityat an changes tenor left ventricle 15 55 M 20 ASHD. diabetes, CA colon NonspecificST & I wave 51 175 245 Moderate increased activity at changes inferior surface of left yen tricle 16 59 F 3 ASHD with unstable an Left bundle branch block 56 110 390 Mild increased activity at gina. cardiomegaly. anterior left ventricle acute pulmonary thromboemboli 17 76 F 5 CA colon, ASHD. diabetes tSR, occasional SVBs 28 115 200 Moderateincreasedactivityat medial inferior border of right ventricle 18 71 F 3 ASHD with unstable angina Right bundle branch block 40 140 295 Mildincreasedactivityat an tenor left ventricle 19 72 M 7 ASHD. CA prostate. S/P Nonspecific ST & T wave 30 100 330 Mildincreasedactivityat In prostatectomy changes ferior surface of left yen. tricle 20 48 M 3 ASHD, cardlamegaly, Old inferior wall myocardial 14 70 260 Mild increased activity at an anxiety reaction infarct—age indeterminate tenor and inferior left ven tide 21 86 F 6 ASHD. cardiomegaly. CA Nonspecific ST & T wave 28 80 160 Mild increased activity at In breast bilateral changes ferior surface of left ventricle 22 70 F 4 ASHD with unstable angina Nonspecific ST & T wave 24 95 240 Moderateincreasedactivityat changes apex of left ventricle 23 59 F 2 ASHD, cardiomegaly. hy. Left ventricular hypertrophy 27 165 290 Mild increased activity at apex pertension. diabetes and anterior left ventricle 24 54 F 3 ASHD with unstable angina, Old anteroseptal myocardial 24 65 340 Mild increased activity at apex deep thrombophlebitis infarct—ageindeterminate of left ventricle in right lower extremity

. Normal valus: SOOT 7—40 units; CPK 0—130 units; LDH 150—400 units.

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gina! episode who were not admitted for suspected -f acute myocardial infarction. Acute infarction was excluded in Group 2 by serial ECGs, serum enzyme studies, and subsequent clinical course. Group 3. Myocardiopathy. Six patients were stud ied: all were men, with an age range of 50—70years. ——,,@:1k. A strong history of alcoholic intake was present in four cases. The diagnosis of myocardiopathy was FIG.2. Unstablearterioscleroticheartdisease(Group2).Note made on clinical grounds. moderate ill-defined nonfocal increased radioactivity in vicinity of left ventricle. RESULTS Group 1. No patient had any history of significant The Group I patients were studied as part of an cardiac disturbance and physical examination did examination for routine bone imaging. They were not disclose cardiac disease. Electrocardiograms all informed that the images of the heart were being were all normal, and the highest SGOT, CPK, and obtained as part of a clinical investigation. LDH values were within normal limits. No myo Group 1. No evidence of cardiovascular disease. cardial activity was found in 19 of the 20 patients Twenty patients were studied: 10 men and 10 studied (Fig. 1). The exception, a 31-year-old women. The age range was 18—69years. All had woman without confirmable cardiac disease, showed history, physical examination, and electrocardio increased tracer uptake at about the inferior and grams. Serum-enzyme determinations included glu apical border of the left ventricle. It was not super tamic-oxaloacetic transaminase (SGOT), lactic de imposed breast activity, which in this patient was hydrogenase (LDH), and creatine phosphokinase localized anterior to the chest wall by a lateral scm (CPK). tigram. The myocardial activity was confined to the Group 2. Arteriosclerotic heart disease without thoracic cavity and did not move with the breast on acute infarcion. Twenty-four patients were studied: the lateral scintigrams. The patient has no known 10 men and 14 women. The age range was 36—87 primary or metastatic malignant disease. We have years. These patients all had angina and some had no explanation for this scintigraphic finding. previous myocardial infarction as indicated by dcc Group 2 (Table 1). All 24 patients had confirma trocardiograms. This group is actually composed tory history and physical findings for ASHD. Each of two subgroups. Approximately one-half were ad was studied 2—20 days after an anginal episode. All mitted with chest pain and the suspicion of acute showed ill-defined faint-to-moderate activity in the myocardial infarction, and the other half were pa region of the anterior or inferior aspect of the left tients with arteriosclerotic disease and a recent an ventricle (Fig. 2). Serial ECG and serum enzymes

TABLE 2. PATiENTS WITH MYOCARDIOPATHY

Pa High High.High tientestestestNo. Age Sex Chestpain Condition ECGfindings SGOTCPKLDH Scintigram

1 50 M None Alcoholic ventricular 80 120 330 increased activity through myocardiopathyLeft hypertrophyFaint out enlarged cardiac silhouette252MNoneAlcoholic bundle increasedactivity through myocardiopathyleft branchblock40140360Faint out enlarged cardiac silhouette359MNoneAlcoholic ventricular increased activity myocardiopathyleft hypertrophy3524240Moderate throughout enlarged cardiac silhouette470MNoneAlcoholic ventricular increased activity through myocardiopathyLeft hypertrophy6070300Faint out enlarged cardiac silhouette577MNoneIdiopathic blockand increased activity myocardiopathyAV incomplete throughout enlarged cardiac silhouette655MNoneIdiopathic right bundle branch block5971270Marked ventricular 10300No increasedactivity myocardiopathyLeft hypertrophy701

Volume 17, Number 4 243 PEREZ, HAYT, AND FREEMAN excluded acute myocardial infarction. For those pa positive at 90 mm, although the activity was some tients who previously had acute myocardial infarc what less intense. The O9mTc4abeled phosphate was tion, clinical history and electrocardiogram dating tested for free technetium at the time of administra could not pinpoint the time of the previous infarc tion, using instant thin-layer chromatography with tion. However, it seemed clear that an interval silica-gel medium and acetone as solvent (6,7) . At greater than 3 weeks had existed between the pre no time was more than 12% of free technetium vious infarction and the subsequent imaging. found, and usually only 5% was present; this is Group 3 (Table 2). The diagnosis of myocardiop comparable to results obtained elsewhere (6,7) . In athy was made on clinical grounds. Five of the six addition, no activity was detected in the thyroid or patients were volunteers from the cardiac clinic and stomach area of any patient. one was an occult case discovered incidentally at the We have no reason to believe that the kinetics of time of bone imaging for an unrelated disorder. None the technetium-labeled polyphosphate and pyrophos of the patients was hypertensive or in cardiac de phate in our patients was in any way different from compensation at the time of imaging. Four patients that reported (7) . It seems unreasonable to assume had confirmatory history and physical findings for that increased and persistent blood-pool activity, due alcoholic myocardiopathy. They all presented with to altered plasma binding or inappropriate labeling out chest pain and with normal SGOT, CPK, and with a phosphate, has occurred in all our patients LDH enzyme values. Electrocardiography showed with arteriosclerotic heart disease and myocardiop left ventricular hypertrophy in three patients. The athy. This is especially unlikely in that 19 normal four patients with alcoholic myocardiopathy showed patients did not show myocardial activity. Moreover, faint-to-moderate diffuse activity throughout the some of the normal patients were injected from the markedly enlarged cardiac silhouette (Fig. 3) . One same batch of radiopharmaceutical as were the pa of the two patients with idiopathic myocardiopathy tients who showed myocardial activity. Persistent showed similar findings. blood-pool activity could also be accentuated in pa tients with chronic renal failure, but of those studied DISCUSSION none had chronic renal failure and only one was in Bonte et al studied patients with arteriosclerotic cardiac decompensation. Another potential pitfall heart disease without acute infarction and found activity in the region of the left ventricle. Myocardial activity with 9OmTc.labeled phosphate agents need not indicate acute myocardial infarction. Myocardial activity has been detected in one out of 20 normal patients and in 24 out of 24 patients with arterio sclerotic heart disease but without acute infarction. Since confusion could arise if poor labeling of the phosphate caused an increase in free technetium and persistent activity in the cardiac blood pool, we corn pared the 90-mm scintigrams with others obtained at 4 hr. The same abnormal myocardial activity was FIG.3. Myocardiopathy(Group3).Notefaintdiffuseincreased observed on the 4-hr studies in all patients who were radioactivity throughout markedly enlarged cardiac silhouette.

TABLE 3. SCINTIGRAPHIC OBSERVATIONS IN MYOCARDIAL ABNORMALITIES USING 99mTc4@BELEDPHOSPHATES

Clinical diagnosis Distribution of activity Intensity of activity

Normal None None Acute myocardial infarct Focal, corresponding to distribution of Moderate to marked occluded vessel ASHD without acute infarct (stable) None None ASHD without acute infarct (unstable), Ill-defined, in region of left ventricle Mild to moderate recent anginal episode Myocardiopathy Diffuse, involves entire radiographic car Usually mild to moderate, occasionally diac contour marked

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lated by the difficulties in infarct diagnosis encoun tered by the standard methods. An extension of this reasoning suggests the exciting possibility that the abnormal uptake in our patients with arteriosclerotic heart disease might conceivably represent areas of subclinical infarction, not confirmable by standard diagnostic tests. Further investigative work should help to confirm or refute this possibility. As with other radionuclide imaging studies, the specificity of the procedure is always enhanced by evaluating the results in conjunction with other clinical considera tions. In addition, careful assessment of the intensity and distribution of the abnormal activity should help to differentiate the entities of acute infarction, ar teriosclerotic heart disease without acute infarction, and myocardiopathy (Table 3, Fig. 4) . We empha size the relatively unstable status of the Group 2 patients. All had recent angina, but no evidence of acute infarction was present. Myocardial imaging with oomTc@labeledphosphate is a simple safe noninvasive technique which may be useful to establish the presence or absence of myo cardial infarction. Whether the localization of tracer detectable by a camera indicates only frank infarction or may also include areas of simple ischemia still remains to be determined. This situation may be similar to that of labeled tetracycline in ischemic myocardium (1 1 ) . Attempts have been made to size acute myocardial infarction in patients using simi FIG.4. Bycomparisonofscintigraphicpatternsof myocardial activity, various disease processes can generally be distinguished. lar methods ( 12) . If it should turn out, however, that the scintigram also signals simple ischemia, the esti mate of “infarctsize―may be too generous. is breast localization of phosphate agents, described by several investigators (8) . The lateral scintigram REFERENCES is particularly helpful in such situations. 1. BONTE FJ, PARKEY RW, GRAHAM KD, et al: A new Bonte et al postulated that myocardial infarction method for radionuclide imaging of myocardial infarcts. induces cellular influx of calcium ions with localiza Radiology 110: 473—474,1974 2. PARKEYRW, BONTEFJ, MEYERSL, et al: A new tion in the mitochondria near the hydroxyapatite method for radionuclide imaging of acute myocardial in. crystal (1 ) . Thus, in myocardial ischemia without farction in humans. Circulation 50: 540—546,1974 infarction, the phosphate tracer may be showing this 3. WILLERSON JT, PARKEY RW, BONTE FJ, et al: Acute intracellular flux of calcium ions from the sarcoplas subendocardial myocardial infarction in patients. Circulation mic reticulum to the mitochondria (9) . These 51: 436—441,1975 4. WILLERSONJT, PARKEYRW, BONTEFJ, Ct al: Tech changes may occur early in myocardial ischemia and netium 99m stannous pyrophosphate myocardial imaging in have been demonstrated before standard clinical the diagnosis of acute myocardial infarction in patients. signs of overt cardiac failure appeared (9) . Simi Circulation 49—50:Suppl No 3, 4, 1974 larly, these intracellular changes associated with the 5. WILLERSONJT, PARKEYRW, BONTEFJ, et al : Tech preclinical stages of cardiac failure may occur in netium stannous pyrophosphate myocardial scintigrams in patients with chest pain of varying etiology. Circulation 51: arteriosclerotic heart disease without overt infarc 1046—1052,1975 tion. It is well known that the “diagnosisof acute 6. BILLINGHURSTMW: Chromatographicquality control myocardial infarction depends on inferential clinical of mmTc-Iabeled compounds. I Nucl Med 14: 793—797,1973 and laboratory data, including the occurrence of 7. KRISHNAMURTHYGT, HUEBOrrERRJ, WALSHCF, chest pain, sequential electrocardiographic changes, et al: Kinetics of ‘@mTc-labeled pyrophosphate and poly and altered pattern in serum enzyme activity―(10). phosphate in man. I Nucl Med 16: 109—115, 1975 8. SERAFINIAN, RASKINMM, ZAND LC, et al: Radio Much of the enthusiasm for 99mTc@labeledphosphate nuclide breast scanning in carcinoma of the breast. I Nucl or tetracycline in myocardial imaging has been stimu Med 14:1149—1152,1974

Volume 17, Number 4 245 PEREZ, HAYT, AND FREEMAN

9. CHIDSEYCA : Calcium metabolismin the normal and 11. POE ND, RoBINsoN GD: Relation between blood f@i1ing heart. In The Myocardium: Failure and Infarction, flow and uptake of labeled tetracycline in ischemic myo Braunwald E, ed, New York, Hospital Practice Publishing, cardium. Clin Res 23: No. 2, 1, 125A, 1975 1974,pp 37—47 12. HARRIS RA, PARKEYRW, BONTE FJ, et al: Sizing 10. HOLMAN LB, LESCH M, ZWEIMAN FG, et al: Detec acute myocardial infarction in patients utilizing technetium tion and sizing of myocardial infarcts with technetium stannous pyrophosphate myocardial scintigrams. Clin Res 99m (Sn) tetracycline. N Engi I Med 291 : 159—163,1974 23: No. 1,3A, 1975

23rd ANNUAL MEETING

THE SOCIETY OF NUCLEAR MEDICINE

June 8—11,1976 Dallas ConventionCenter Dallas, Texas

Members and nonmembers of the Society of Nuclear Medicine are invited to attend the 23rd An nual Meeting. The convenience and comfort of attendees will be emphasized as much as possible, with good food service,snackbars, and lounge areas readily available in the ConventionCenter.Thisyear's program will include lectures by distinguished scientists in specialty areas as well as selected research papers of merit. Due to the popularity of the teaching sessions,the format has been expanded so that teaching is not confined to the early morning hour, but is distributedthroughout the daily program.

A wide variety of nuclear medicine topics in clinical research, clinical practice, and basic science will be covered,including the following: Bone/Joint,Cardiovascular,Computer/DataAnalysis,Computer ized Axial Tomography, Dosimetry, Endocrine/Metabolism, Gastroenterology, Hematology, Instrumenta tion, In Vitro Assays, Neurology, Oncology, Pediatrics, Pulmonary, Radiopharmaceuticals, and Renal! Electrolytes. Scientific sessions for the Technologist Section will be held concurrently.

Registration forms are available from the Society of Nuclear Medicine, 475 Park Avenue South, New York, N.Y. 10016.

J

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