Tc-99m Pyrophosphate Research Articles

Automatic implantable cardioverter/defibrillator discharges and acute myocardial injury.

Multiple defibrillations by the automatic implantable cardioverter/defibrillator (AICD) have been reported to result in localized epicardial damage. No data exist, however, regarding whether this damage can be detected in the clinical setting or whether it interferes with the detection of true myocardial infarction. Forty-nine patients who received defibrillations by patch electrodes were studied prospectively. We attempted to document the presence of myocardial injury with the following three commonly used modalities for the detection of myocardial infarction: serial electrocardiographic changes, serial creatine phosphokinase (CPK) and CPK-MB release, and technetium 99m pyrophosphate scanning. Fifteen patients received defibrillations by AICD patches at the time of AICD generator replacement. Nine patients received defibrillations at the time of new AICD lead placement. The average total energy delivered was 85 +/- 29 J. None of these patients had detectable myocardial injury. Ten patients had defibrillations by the AICD patches at the time of bypass operation. One patient in this group developed acute myocardial infarction in the inferior wall after posterior descending coronary bypass operation, as detected by electrocardiogram, 99mTc pyrophosphate scanning, and CPK-MB analysis. Fifteen patients were evaluated for spontaneous AICD discharges. Thirteen had a maximum of five consecutive shocks, and cumulative energy delivered was not greater than 330 J. None of these patients had detectable injury. Two patients had CPK-MB release of 15.3% and 7.5%, respectively. One of these patients had a positive 99mTc pyrophosphate scan. These two patients received 12 and 17 rapid and consecutive AICD discharges, respectively, with cumulative delivered energy of 360 and 510 J, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of In-111 antimyosin Fab and 99mTc-pyrophosphate in reperfusion myocardial infarction model.

The myocardial uptake of In-111 antimyosin Fab and Tc-99m pyrophosphate was studied in dogs undergoing coronary artery occlusion for 90 minutes followed by reperfusion. The regional myocardial blood flow was determined by injecting Sc-46 labeled microsphere and was related to the relative concentrations of In-111 antimyosin and Tc-99m pyrophosphate.There was an inverse linear correlation between In-111 antimyosin Fab localization and the regional blood flow in both the subendocardial (r = 0.81) and subepicardial myocardium (r = −0.80). The greatest uptake of antimyosin was observed in areas of severe blood flow reduction (0–10% of normal).On the other hand, there was no correlation between the Tc-99m pyrophosphate uptake and the degree of blood flow reduction. Maximal subendocardial localization of Tc-99m degree of blood flow reduction. Maximal subendocardial localization of Tc-99m pyrophosphate was observed in areas where the blood flow was reduced to 31–50% of the normal. In the case of the subepicardium, the greatest uptake was localized to areas of 0 to 10% of the normal flow. In addition, there was significant myocardial uptake in regions where the blood flow was minimally reduced (>81%). This study suggests that In-111 antimyosin Fab is a specific and quantitative tool in the evaluation of myocardial necrosis.

Tc-99m Pyrophosphate Localization in Chest Wall Muscles After Bench Pressing

Tc-99m Pyrophosphate Localization in Chest Wall Muscles After Bench Pressing

Extensive Extraosseous Localization of Bone Imaging Agent in a Patient with Renal Failure and Rhabdomyolysis Accompanied by Combined Hypercalcemia and Hyperphosphatemia

Four sequential Tc-99m pyrophosphate (PYP) imaging studies were performed in a 28-year-old man with high fever and exudate pharyngitis associated with renal failure. Radiotracer localization in the left ventricle (LV), lungs, kidneys, and skeletal muscles were seen in two, initial imaging studies. In the second and third imaging studies, area of increase in activity was seen in the left-sided bowel. In studies done two months later (in the third study), the radioactivity in the skeletal muscles was no longer seen. Studies obtained nine months (in the fourth study) after the first imaging showed less radiotracer localization in the LV, lungs, and kidneys as compared to that seen in the initial study. Myocardial necrosis and microcalcification were proved by LV biopsy. The exact mechanism of extraosseous bone-imaging agent localization is unknown. However, this phenomenon may be related to renal failure, rhabdomyolysis, hypercalcemia, hyperphosphatemia, or elevated parathyroid hormone. The Tc-99m PYP imaging study is useful and sensitive in the detection of extraosseous tissue calcification and monitoring of the disease process.

99mTc Pyrophosphate Knee Scintigraphy as a Diagnostic tool for the Tear of the Meniscus of the Knee

99mTc Pyrophosphate Knee Scintigraphy as a Diagnostic tool for the Tear of the Meniscus of the Knee

Cardiac nuclear medicine

In this paper, the principal applications of nuclear medicine to studies of the heart are described. First, gated cardiac blood pool imaging is discussed, then thallium-201 myocardial imaging, myocardial infarct scintigraphy with 99mTc pyrophosphate, and evaluation of intracardiac shunts. In gated cardiac blood pool imaging, the patient's red blood cells are labeled with 99mTc. Images of the cardiac blood pool are then obtained in multiple projections and displayed in an endless-loop cine display. Quantitative indices of cardiac function are readily obtained, and a variety of functional images can be generated. Blood pool imaging may also be performed with use of a first-pass technique that yields similar information. Applications of blood pool imaging are discussed. The theory and techniques of planar and tomographic thallium-201 myocardial imaging are described, together with their application in the diagnosis of coronary artery disease. The prognostic value of thallium imaging is also examined. Myocardial infarct imaging with 99mTc pyrophosphate is described, and clinical indications are reviewed. Left-to-right cardiac shunts can be evaluated by following the first transit of a bolus of radiopharmaceutical through the lungs. Right-to-left shunts may be evaluated by injection of 99mTc macroaggregated albumin.

Muscle necrosis in the extremities: evaluation with Tc-99m pyrophosphate scanning--a retrospective review.

A retrospective review was done of 34 extremities studied between 1981 and 1985 with technetium-99m pyrophosphate scanning; 22 were subsequently amputated. Results of detailed pathologic examination or immediate postoperative examination of the resected extremity were available in 16 cases. In these cases, scanning had allowed correct prediction of the level of amputation and of the specific areas of muscle infarction in 13 cases. In the one case in which amputation was performed for infection rather than muscle necrosis, the lack of necrosis was correctly predicted with the scan. The limited results of this study indicate that the Tc-99m pyrophosphate scan allows the location of necrotic muscle to be predicted accurately and may therefore be a useful adjunct in determining the best level for ultimate amputation. Special caution is required in those cases in which muscle necrosis is due to acute causes (e.g., traumatic thrombosis) rather than chronic vascular disease.

99mTc bone scanning agents—VI. Gel chromatographic analysis of the plasma protein binding of 99mTc(Sn)pyrophosphate, 99mTc(Sn)MDP and 99mTc(Sn)HMDP

The plasma binding of Tc-complexes of pyrophosphate, MDP and HMDP was investigated in vitro usinggel chromatography on Biogel P-200. Binding percentages ranging from 5–15% were found. The pH of the preparation of the radio-pharmaceutical had a large effect on the protein binding. The differences between the three ligands used were small. The chemical composition of the complexes was investigated for Tc(Sn)pyrophosphate using gel chromatography on Biogel P-4. The protein-bound technetium was not attached to pyrophosphate. The chemical composition of the unbound Tc-complex is discussed. Finally a comparison is made with literature data. It is concluded that protein binding plays a minorrole.

Quantitation of postischemic skeletal muscle necrosis: Histochemical and radioisotope techniques

Skeletal muscle necrosis will result from prolonged periods of ischemia. The purpose of this study was to develop a method to estimate the extent of necrosis using nitroblue tetrazolium staining and technetium scanning. The bilateral canine gracilis muscle preparation with total vascular isolation was exposed to 4 hr of complete normothermic ischemia followed by reperfusion. After 45 hr of reperfusion 99mTc pyrophosphate (PYP) was injected and 3 hr later the muscles were harvested, cut into six slices, and stained with nitroblue tetrazolium. Biopsies were taken from tetrazolium-positive and -negative areas for electron microscopy to confirm the ability of the stain to distinguish viable from necrotic muscle. Computerized planimetry of the staining pattern was used to estimate the extent of necrosis as a percentage of the total muscle. Electron microscopy confirmed the validity of nitroblue tetrazolium to discriminate between viable and necrotic skeletal muscle in this experimental model. After 4 hr of ischemia the percentage necrosis was 30.2 ± 6.1% (mean ± SEM, n = 12), there was no difference in the extent of necrosis in left vs right paired muscles, using tetrazolium staining or technetium PYP uptake. There was a statistically significant correlation between the percentage necrosis and the density of 99mTc PYP uptake per muscle ( r = 0.83, P < 0.001) and per slice ( r = 0.94, P < 0.001). This study demonstrates the ability of tetrazolium staining to accurately differentiate between viable and necrotic skeletal muscle and provides a reproducible method for estimating the extent of necrosis in the gracilis muscle model.

Relationship between TI-201, Tc-99m (Sn) pyrophosphate and F-18 2-deoxyglucose uptake in ischemically injured dog myocardium

We have previously demonstrated that enhanced glucose utilization in reperfused myocardium as assessed by F-18-2-deoxyglucose (FDG) and positron tomography predicts functional recovery. In this study, we compared segmental uptake of F-18 FDG with that of TI-201 and Tc-99m (Sn) pyrophosphate (Tc-99m PPi) as conventional markers of tissue viability in seven dogs after a 3-hour intracoronary balloon occlusion and 20 hours of reperfusion. Myocardial blood flow was determined with microspheres. Regional retention fractions were calculated from tracer tissue concentrations, the arterial input function, and blood flow. ischemic injury was assessed by triphenyltetrazolium chloride (TTC) staining and histologic analysis. At 24 hours, blood flow was 22% lower in reperfused than in control myocardium ( p < 0.05). Uptake of TI-201 was related linearly to blood flow ( r = 0.92), while glucose utilization and Tc-99m PPi were 2.9 ( p < 0.01) and 4.7 ( p < 0.05) times higher in reperfused than in control myocardium. Retention fractions of Tc-99m PPi increased with the degree of ischemic injury, while F-18 FDG uptake was highest in segments with mild cell injury. Thus, in ischemically injured myocardium, TI-201 primarily reflects blood flow. F-18 FDG as a marker of glucose utilization identifies ischemically injured but viable tissue. The admixture of necrotic cells can be determined with Tc-99m PPi. Our results indicate that a dual tracer approach might best characterize the presence and extent of reversibly and of irreversibly injured tissue in a given myocardial region.

The extent and distribution of skeletal muscle necrosis after graded periods of complete ischemia.

The management of an acutely ischemic extremity requires knowledge of the response of skeletal muscle (the largest component of the lower limb) to prolonged periods of complete normothermic ischemia. We have used the canine gracilis muscle model to evaluate the extent and distribution of ischemic necrosis after 3 and 5 hours of ischemia and 48 hours of reperfusion. Each muscle was cut into six slices, and the extent and distribution of postischemic necrosis identified by means of nitroblue tetrazolium staining and 99mTc pyrophosphate uptake. After 3, 4, and 5 hours of ischemia the extent of necrosis was 2.0% +/- 0.9%, 30.3% +/- 6.0%, and 90.1% +/- 3.5% (mean +/- SEM), respectively. A statistically significant correlation exists between the extent of necrosis and the uptake of 99mTc pyrophosphate uptake per gram of tissue (y = 1574.9x - 8.4, r = 0.84, p less than 0.001). Most necrosis was centrally located and found in the thickest portion of the muscle. We conclude that there is a graded response in the extent of skeletal muscle necrosis related to the length of ischemic stress rather than an "all-or-none" phenomenon. This central distribution of necrosis makes the usual external evaluation of ischemic damage clinically unreliable. In addition, since there was no enveloping fascia in this model, a compartment release alone may not prevent the development of skeletal muscle necrosis. This knowledge of the response of skeletal muscle to ischemia may lead to an improved clinical approach to an extremity suffering a prolonged ischemic insult.

Frostbite: experimental assessment of tissue damage using Tc-99m pyrophosphate. Work in progress.

We designed an experimental model using a new method of freezing to study the pathogenesis and treatment of frostbite. Frostbite was simulated in a manner that closely resembles that which occurs in a natural environment. We used a radionuclide imaging technique to monitor the evolution and extent of tissue damage relative to temperature, rate of freezing, and controlled rewarming. Characteristic sequential changes were demonstrated on sequential nuclear scans. Nonperfusion, followed by perfusion, and finally again by nonperfusion occurred in all areas in which necrosis developed. The reappearance of nonperfusion corresponded to vascular injury and thrombosis evidenced at pathologic examination. We determined that lack of tissue perfusion corresponded to tissue injury. We believe that our experimental model provides an effective means of evaluating potential therapeutic regimens.

99mTc bone scanning agents—II. Adsorption of 99mTc(Sn)pyrophosphate complexes on the mineral phase of bone

The adsorption of pyrophosphate, tin-pyrophosphate and 99mTc(Sn)pyrophosphate on Ca3(PO4)2 was investigated at pH 4.0 and pH 7.4. All components were radioactively labeled. Tin and reduced technetium were in most cases almost completely bound. The adsorption of pyrophosphate, tin(II) and technetium-99m at pH 4.0 was higher than at pH 7.4. The presence of tin gave rise to an increase of the pyrophosphate adsorption that was much larger than can be accounted for by a stoichiometric adsorption of tin-pyrophosphate. It is concluded that tin and technetium are bound as negatively charged complexes with pyrophosphate. Finally it is argued that the fraction of the bone scanning agent that reaches the bone surface is adsorbed completely by the mineral phase.

99mTc bone scanning agents—III. Preparation and gel chromatography of 99mTc(Sn)MDP complexes

The preparation of 99mTc(Sn)MDP was investigated as a function of pH, MDP concentration and Sn(II) concentration. The labeling efficiency was over 90% in the majority of the experiments and remained constant over the range pH 2-9. The MDP concentration had little effect, while the Sn(II) concentration had a significant positive influence. The complex formation appeared to be partly reversible. The formation of different complexes was investigated by means of gel chromatography under various experimental conditions. Altogether six complexes were found. At acid conditions two major complexes were found and at neutral pH one major complex. The presence or absence of a particular complex was mainly determined by the pH and by the MDP concentration. The Sn(II) concentration had very little effect. The results are compared with previous results of similar experiments with 99mTc(Sn)pyrophosphate.

Sequential uptake patterns of technetium-99m pyrophosphate in hepatoma.

Sequential liver scintiphotography with Tc-99m pyrophosphate (PYP) was used to prospectively evaluate its uptake patterns in hepatoma. The scintiphotos and time-activity curves of 40 cases were analyzed. Two distinct patterns of tumor activity were noted: gradual but complete extraction and trapping of Tc-99m PYP in hepatoma in 38% of the patients (group 1), and absence of subsequent Tc-99m PYP uptake in hepatoma after initial blood pool activity in 62% of the patients (group 2). Since extraction and trapping of Tc-99m PYP occur approximately in two fifths of the patients with hepatoma, we conclude that Tc-99m PYP liver scintigraphy is not worthwhile supplementing the conventional radionuclide studies for diagnosing hepatoma, even in the selected patients in the countries where the prevalence of hepatoma is high.

Selective, Symmetric, Skeletal Muscle Uptake of Tc-99m Pyrophosphate in Rhabdomyolysis

From the Department of Radiology, Division of Nuclear Medicine, Stanford University Medical Center, Stanford, California

Applications of anticardiac myosin monoclonal antibodies in the diagnosis of heart disease.

We have developed anticardiac myosin antibodies, especially monoclonal antibodies, for helping in the diagnosis of heart disease. Our investigations were divided into three research projects. We visualized the distribution of myosin isozymes in human atrial and ventricular myocardium by an immunofluorescence staining method using monoclonal antibodies specific for individual human cardiac myosin isozymes. We also revealed the redistribution of these cardiac myosin isozymes in an overloaded condition. The isozymic pattern of cardiac myosin was changed from the atrial type to the ventricular type in the overloaded atrium. This isozymic redistribution can be considered as physiological adaptive mechanism to meet increased cardiac work during overload. We developed a new method of imaging for myocardial infarction by single photon emission tomography using labelled monoclonal antibody specific for cardiac myosin heavy chain. Specific localization of the labelled antibody was demonstrated in the infarcted area and no accumulation of radioactivity was shown in the bone matrix as observed in 99mTc pyrophosphate images. We developed a sensitive radioimmunoassay of cardiac myosin light chain I (LCI) and demonstrated that peak serum levels of LCI in the patients with acute myocardial infarction correlated well with the left ventricular ejection fraction. Furthermore, LCI release from the infarcted myocardium was not affected by coronary reperfusion due to intracoronary thrombolysis. Thus, serial determinations of serum LCI better quantify the extent of myocardial damage even after coronary reperfusion in acute myocardial infarction.

EVALUATION OF 99mTc PYROPHOSPHATE TO DIAGNOSE ACUTE CARDIAC REJECTION IN THE RAT WITH STUDIES ON THE EFFECT OF CYCLOSPORINE

Uptake of 99mTc pyrophosphate (PYP) has been shown to be a sensitive and specific indicator of ischemia myocardial injury. We investigated the uptake of 99mTc PYP during acute cardiac rejection in an experimental model of heterotopic transplantation in the rat. The model allowed comparison of uptake of PYP between the transplanted and the recipient's native heart, and the results were corrected for weight and expressed as a ratio: Transplanted/Native. Four groups of ratio were studied: Group 1 (N = 6) was between animals of isogeneic strain and the ratio of uptake was 1.85 ± 0.9 (M ± SD) which was significantly different from the ratio of 3.23 ± 0.96 in Group 2 (N = 11) in which transplants were between non-isogeneic animals (P<0.01). Group 3 (N = 7) were non-isogeneic animals treated with Cyclosporine 10 mg/Kg/day and the ratio 2.14 ± 0.5 was not different from Group 1, but was statistically different from Group 2 (P< 0.01). In contrast the ratio of uptake between non-isogeneic animals treated with subtherapeutic doses of Cyclosporine (1mg/Kg/day) Group 4 (N = 4) was 2.81 ± 0.6 which was not different from Group 2. In groups 1, 2 and 3 there was correlation between the histology of the transplanted hearts graded 1 to 5 blindly according to the severity of rejection and the uptake of 99mTc PYP. 99mTc PYP can therefore be used to diagnose cardiac rejection in a rat model, and the results correlate well with the severity of rejection as assessed histologically.

The use of gated radionuclide angiography in the diagnosis of cardiac contusion

No currently used diagnostic test is an accurate predictor of patients who will develop morbidity or mortality from cardiac contusion. In a prospective study we used gated cardiac radionuclide angiography to assess cardiac function in 30 patients with blunt chest trauma, and we compared the results of this test with those of other diagnostic studies for cardiac contusion to determine whether gated angiography is a more accurate predictor of serious cardiac injury. Diagnostic tests included the following: serial electrocardiograms (ECG), serial creatine phosphokinase muscle-brain isoenzyme (CPK-MB) and lactic dehydrogenase (LDH) isoenzymes, gated cardiac radionuclide angiography, and technetium-99m (Tc-99m) pyrophosphate scintigraphy. Abnormal studies were present in 26 patients; 22 showed abnormalities in CPK-MB, 19 on ECG, and five on gated scan. No patient demonstrated an abnormal Tc-99m pyrophosphate scan or abnormal elevation of LDH isoenzyme. Although no diagnostic test was predictive of morbidity and mortality, CPK-MB isoenzyme was the only test to correlate with morbidity and mortality. Morbidity and mortality correlated most closely with the number of associated major injuries and the presence of hypotension or hypoxia.

Effects of mechanical loading on the tissues of the rabbit knee.

We studied changes in subchondral bone and articular cartilage in an animal model of osteoarthrosis. In this model we applied repetitive impulsive loads to rabbits' knees. Their legs were held in short leg splints so the rabbits were unable to dampen the peak applied load with ankle flexion. After sacrifice, at 1 day to 6 weeks, we studied proximal tibial load-bearing cartilage histologically, biochemically, and with radioactive sulfate uptake. We also studied the subchondral bone under that cartilage histologically, histomorphometrically, with bone scan (99mTc pyrophosphate), and by tetracycline labeling. An increase in 99mTc labeling of the subchondral bone was the first reliable change observed. This was followed by an increase in tetracycline labeling, bone formation, and a decrease in porosity, which has been associated with relative stiffening of bone. Horizontal splitting and deep fibrillation of the overlying articular cartilage followed the early bone changes. All of these changes preceded changes in content and characterization of cartilage proteoglycans or increased chondrocyte activity as manifested by incorporation of radioactive sulfate. In this model the early bone changes preceded changes in the articular cartilage. The deep splitting of articular cartilage occurred prior to metabolic alteration of that tissue.