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Imaging necrotic myocardium: detection with 99mTc-pyrophosphate and radiolabeled antimyosin.

The major value of hot-spot imaging of the myocardium is its ability to define areas of necrosis rather than areas of diminished blood flow or cellular function. Applications of hot-spot imaging include the diagnosis and quantitation of myocardial infarction, myocarditis, and cardiac transplant rejection. The two agents in clinical use, 99mTc-Pyrophosphate and radiolabeled antimyosin, are discussed.

Animals↗

[Quantification of myocardial infarct size by technetium-99m pyrophosphate single photon emission computed tomography].

Myocardial infarct size in 41 patients with the first attack of acute transmural myocardial infarction (MI) was assessed by technetium-99m pyrophosphate single photon emission computed tomography (99mTcPYP-SPECT). A ratio of the number of voxels of 99mTcPYP uptake into the infarct area to that into the thorax was calculated as a parameter of MI size. The ratio was positively correlated with both peak CPK activity (r = 0.53, p less than 0.005, n = 24) and extent score in 201TI-SPECT (r = 0.70, p less than 0.005, n = 14) significantly in patients with anterior MI but not in patients with inferior MI. There was also significant negative correlation between the ratio and the left ventricular ejection fraction (LVEF) measured by RI angiography in both acute (r = -0.67, p less than 0.005, n = 18) and chronic (r = -0.75, p less than 0.005, n = 25) phases in patients with anterior MI. Recovery in LVEF at chronic phase was noted in patients with small anterior MI but not with large anterior MI. 8 of 14 patients with inferior MI had right ventricular MI, that might have affected evaluation of MI size and resulted in no correlation between variables. It was suggested that 99mTcPYP-SPECT was a useful method to evaluate MI size and to predict prognosis of cardiac function in patients with anterior MI but not in patients with inferior MI.

Adult↗

[Diagnostic possibilities of static gamma-scintigraphy using 99mTc pyrophosphate and Tc 99m phosphate in children with glomerulo nephritis].

Children with nephrotic glomerulonephritis were examined for incorporation of 99mTc-pyrophosphate and 99mTc-phosphone. The relationship was discovered between the accumulation of the radiopharmaceutical drug and the sensitivity to glucocorticoids used in the pathogenetic treatment. Accumulation of the drug in the course of the treatment documents the presence of complete, partial remission or the disease activity. It is recommended that static gammascintigraphy should be carried out for early assessment of the efficacy of the treatment and its correction.

Adolescent↗

Calcium pyrophosphate and monosodium urate crystal interactions with neutrophils: effect of crystal size and lipoprotein binding to crystals.

"Small" (between 75-98% of crystals less than or equal to 10 microns) and "large" (between 81-93% of crystals greater than 10 microns) size fractions of monosodium urate monohydrate (MSUM) and calcium pyrophosphate dihydrate triclinic (CPPD) crystals were incubated with human neutrophils and crystal induced neutrophil cytolysis monitored by measuring the release of lactate dehydrogenase. "Small" size fractions of MSUM and CPPD gave higher percent lysis values than "large" crystals. The binding of high density lipoproteins (HDL) and low density lipoproteins (LDL) to the crystals was quantitated. HDL and LDL bound in significant amounts to both CPPD and MSUM and strongly inhibited CPPD and MSUM induced neutrophil cytolysis. We propose that HDL and LDL bound to MSUM and CPPD may play important roles in the regulation of gouty inflammation.

Apolipoproteins↗

The contribution of 99mTc-pyrophosphate tomoscintigraphy in the evaluation of necrotic myocardial lesions.

Diagnostic contribution of Conventional Planar Scintigraphy (CPSc) and Single Photon Emission Computed Tomoscintigraphy (SPECT), using 99mTc-Pyrophosphate (99mTc-PYP), have been compared in 49 patients with either transmural (T.I., N = 40), or non-transmural (N.T.I., N = 9) infarction. Sensitivity ratios were, respectively for CPSc and SPECT, 75% and 100% in T.I., 78% and 88% in N.T.I. CPSc was non-diagnostic in 6 out of 49 patients, SPECT in only 1. Extent of the necrotizing process was better delineated on SPECT studies than on CPSc. Specificity of 99mTc-PYP tomoscintigraphy evaluated in a group of 6 young (under 40 years old) normal patients was 6/6 (100%). In nine out of ten additional patients without proven infarction who had underwent contrast coronarography within two weeks after a positive 99mTc-PYP SPECT study, significant stenosis (greater than 50%) were found on arteries supplying blood to pathologic territories as demonstrated on tomoscans. It is concluded that 99mTc-PYP SPECT is a very sensitive and specific way--better than CPSc--in the diagnosis as well as in the evaluation of the extent of necrotic myocardial process.

Aged↗

[The pathophysiologic basis for the incorporation of 99mTc-pyrophosphate into myocardial infarct].

The investigation studied the relation of 99mTc-pyrophosphate incorporation (99mTc-PYP) into experimental, 48-hours old myocardial infarction in dogs to tissue vascular supply and to the extent of necrotic tissue. The experimental myocardial infarction was induced in five animals during an operation by the ligation RIVA. The myocardial blood supply was measured in tissue samples, taken from transverse sections of the infarction by means of 86Rb captation. The extent of myocytolysis was measured by depletion of tissue creatine kinase (CK). In the subendocardial layer of the infarction it became obvious that 99mTc-PYP incorporation was proportional to the decrease of tissue blood supply. No relation between the extent of necrosis and the incorporation of the radioactive chemical was demonstrated. The accumulation of 99mTc-PYP requires the necrosis to be present, but its extent apparently does not influence the intensity of incorporation. In the subepicardial infarction layer there was neither a relation of the radioactive chemical cumulation to the blood flow, nor to the extent of the necrosis proved.

Animals↗

[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 Disease↗

[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.

Adult↗

[Noninvasive diagnosis of cardiac involvement by technetium-99m-pyrophosphate (Tc-99m PYP) myocardial scintigraphy in 2 cases of familial amyloid polyneuropathy and 1 case of secondary amyloidosis].

To validate the significance of technetium-99m-pyrophosphate (Tc-99m PYP) myocardial scintigraphy in diagnosing cardiac amyloidosis, 2 patients with familial amyloid polyneuropathy (FAP) and 1 patient with amyloidosis secondary to chronic rheumatic arthritis were studied. All three patients had echocardiographic abnormalities, which were increased wall thickness of the interventricular septum and the left ventricular posterior wall, and granular sparkling appearance in the septum. In 2 patients with FAP, abnormal myocardial uptake of Tc-99m PYP was diffusely detected in Tc-99m PYP SPECT. In the remaining 1 patient with secondary amyloidosis, however, Tc-99m PYP SPECT showed no abnormality, although we had confirmed the presence of myocardial amyloid deposits (type AA amyloid protein) with high amount in the histological examination. Thus, these results indicate that Tc-99m PYP scintigraphy may have a limitation in detecting cardiac involvement in secondary amyloidosis although it is useful in FAP.

Adult↗

Bartter's syndrome and chondrocalcinosis: a possible role for hypomagnesemia in the deposition of calcium pyrophosphate dihydrate (CPPD) crystals.

A new case of association between Bartter's syndrome and chondrocalcinosis is reported. The patient was shown to have marked hypomagnesemia. Indomethacin and magnesium therapy was started and resulted in increased magnesemia, even if it did not reach normal levels. There was complete remission of articular symptoms and no progression on the radiological picture after 2 years of continuous magnesium and indomethacin therapy. The 7 available family members were studied to assess the possible presence of a familial form of chondrocalcinosis and/or hypomagnesemia. The literature is reviewed and reports of previously described associations between Bartter's syndrome and chondrocalcinosis are summarized. The possible role of hypomagnesemia in predisposing to deposition of calcium pyrophosphate dihydrate crystal in cartilagine is also discussed.

Adult↗

[Infarct size in patients with acute myocardial infarction estimated by emission computed tomography with technetium-99m pyrophosphate: relation to creatine phosphokinase release].

To evaluate the usefulness of single photon emission computed tomography (SPECT) with technetium-99m-pyrophosphate (99mTc-PYP) for estimating infarct size, we compared SPECT data with maximum creatine phosphokinase values. Background threshold was established in a series of phantom experiments. When a 40% cut-off was applied, the SPECT data most closely approximated actual phantom volumes. Therefore, the 40% cut-off level was used in the present study. In 10 patients with acute myocardial infarction, planar 99mTc-PYP myocardial scintigraphy and SPECT using a rotating gamma camera were performed two days after the initial myocardial infarction episode. The maximum creatine phosphokinase value (CPKmax) was also measured repeatedly following the episode. When the infarct size measured by SPECT using transaxial images and calculated by the pixel counts, it correlated very closely with CPKmax (r = 0.94). Most studies so far have reported that the CPKmax level reflects infarct size. We conclude that the infarct size as measured by 99mTc-PYP SPECT closely approximates the actual infarct size, and that this method is useful to determine the severity of infarcts clinically. Among the 10 patients in this series, three of five with infarcts greater than 60 ml died of pump failure. Therefore, we may be able to predict prognosis after accumulating more such cases and improving the methodology.

Aged↗

Characterization and membranolytic effects of triclinic calcium pyrophosphate dihydrate crystals.

The effects of incubation time and buffers of differing phosphate concentration on the ability of well characterized, synthetic triclinic calcium pyrophosphate dihydrate (CPPD) crystals to cause hemolysis of erythrocytes were determined. Maximum hemolysis was attained between 8-11 h; the percent hemolysis was 79% at a high crystal concentration of 50 mg/ml. The percent hemolysis values decreased with increasing phosphate concentration, which may have been due to adsorbed phosphate ions partially masking or protecting the erythrocyte membrane from a binding interaction with CPPD crystals. CPPD crystals possessed a significant negative surface potential, and we postulate that the CPPD crystal-membrane interaction may be mediated via an electrostatic mechanism.

Calcium Pyrophosphate↗

Ferrous [Fe++] but not ferric [Fe] ions inhibit de novo formation of calcium pyrophosphate dihydrate crystals: possible relationships to chondrocalcinosis and hemochromatosis.

To determine the physical-chemical effects of [Fe++] and [Fe ] on calcium pyrophosphate dihydrate (CPPD) crystal formation de novo, we studied CPPD crystal formation in an established model aqueous solution mixture system using physiological concentrations of Na+, Mg++, Ca++, C1-. We found that [Fe++] greater than 1 microM or [Fe ] greater than or equal to 100 microM inhibits CPPD crystal formation under conditions of [Ca++] = 1.5 mM, [Pi] = 0.1 mM, and [PPi] = 0.1 mM that simulate CPPD formation in vivo. These experiments suggest that at biological concentrations, Fe++ acts to inhibit CPPD formation but that [Fe++] depletion therapy by removal of inhibition effects may facilitate CPPD crystal formation in articular tissues.

Calcium Pyrophosphate↗

Calcium pyrophosphate crystal deposition in hyaline cartilage. Ultrastructural analysis and implications for pathogenesis.

Using transmission electron microscopy, selected area electron diffraction, and micro x-ray diffraction techniques, we studied calcium pyrophosphate dihydrate (CPPD) deposits from 23 patients with chondrocalcinosis affecting the femoral head to delineate the cellular and matrix environment in which CPPD crystals form, to determine the sequence of crystal deposition, and to address the question of coexistent calcium apatite crystal deposition. We found 2 types of CPPD crystal deposits with few transitional forms. First, small collections of crystals were seen at the border of the territorial matrix at the articular and subarticular poles of the chondron. CPPD crystal deposits were unassociated with collagen or matrix vesicles. Second, and more frequently, large collections of randomly arranged crystals (agglomerates) were observed, the smallest replacing the chondrocyte and adjacent pericellular matrix. Chondrocytes adjacent to crystal deposits were intact. Coexistent apatite crystal deposition was demonstrated in only 2 of 23 cartilages ultrastructurally examined, providing evidence that mixed crystal deposits are possible but not common in CPPD crystal arthropathy.

Aged↗

Clinical aspects of calcium pyrophosphate dihydrate crystal deposition.

CPPD deposition occurs in a wide variety of clinical settings, most commonly as an age-related phenomenon in the absence of other joint abnormality. Although our knowledge of CPPD and other intra-articular particles has increased in the last decade, the role of CPPD remains unclear. The paradox of asymptomatic deposition of phlogistic crystals, the wide spectrum of clinical presentation, and the lack of disease specificity, however, have challenged recognition of pyrophosphate arthropathy (PA) as a separate, distinct disease entity and led to reappraisal of earlier concepts of crystal deposition disease. In this article, clinical aspects of PA will first be presented; the validity of PA as a discrete arthropathy will then be discussed.

Arthritis↗

Comparison of technetium-99m pyrophosphate and technetium-99m DTPA aerosols for SPECT ventilation lung imaging.

Although [99mTc] diethylenetriaminepentaacetic acid (DTPA) is currently the most widely used radioaerosol, rapid alveolar clearance limits its usefulness for single photon emission computed tomography (SPECT) ventilation lung imaging. Previous research has shown that [99mTc]phosphate compounds have high alveolar deposition and slow clearance and thus provide suitable aerosols for pulmonary ventilation studies. We have compared the pulmonary retention and blood levels of [99mTc]pyrophosphate (PYP) and [99mTc]DTPA in eight normal nonsmoking male volunteers. These two radioaerosols have comparable pulmonary deposition. Technetium-99m PYP, however, has a much slower pulmonary clearance which allows sufficient time (20 or more minutes) for SPECT data acquisition using a single-headed rotating gamma camera. While the radiation absorbed dose to the lungs for [99mTc]PYP (0.31 rad/mCi) is greater than for [99mTc]DTPA (0.11 rad/mCi), it is at a clinically acceptable and safe level.

Administration, Inhalation↗

Peripheral nerve entrapment at the wrist in pyrophosphate arthropathy.

Of 200 consecutive patients with confirmed pyrophosphate arthropathy, clinically significant median nerve entrapment was found in 14 (14%) of those with wrist involvement. Three of these had electromyographically confirmed combined median and ulnar nerve entrapment at the wrist (bilateral in 2). Chondrocalcinosis, but not changes of arthropathy, was closely associated with the presence of entrapment (p less than 0.001), implying that soft tissue factors are important in causation. Treated hypothyroidism was more common in those with nerve entrapment (p less than 0.01), suggesting a possible interaction of multiple factors in the pathogenesis of nerve entrapment.

Adult↗