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Assessment of "microvascular no-reflow phenomenon" using technetium-99m macroaggregated albumin scintigraphy in patients with acute myocardial infarction.

OBJECTIVES: The aim of this study was the scintigraphic evaluation of clinical no-reflow phenomenon. BACKGROUND: In patients with acute myocardial infarction, the relationship of the severity of reduction of microvascular reflow to the ischemia time or to the secondary extension of myocardial necrosis is poorly understood, and we accordingly conducted a scintigraphic evaluation of clinical no-reflow phenomenon. METHODS: The group studied consisted of 25 consecutive patients with their first acute myocardial infarction. After recanalization, each patient received intracoronary injections of technetium-99m macroaggregated albumin (MAA). RESULTS: Eight patients (32%) had absent tracer uptake (scintigraphic no-reflow phenomenon). Fourteen patients showed absent or moderately reduced MAA uptake (group 1) and 11 showed slightly reduced or normal uptake (group 2). The time to recanalization was significantly longer in group 1 than in group 2 (290.4+/-130.6 min vs. 1773+/-93.5 min; p=0.0238). In chronic phase, the thallium-201 (TI-201) defect score index was significantly larger (p < 0.01) and regional ejection fraction was significantly lower (p < 0.01) in group 1 compared with corresponding values in group 2. No significant deterioration from acute phase to chronic phase in either TI-201 defect score index or regional ejection fraction was found in either group (two-way repeated measures analysis of variance). CONCLUSIONS: These findings suggest that scintigraphic noreflow phenomenon occurs in a subgroup of patients without angiographic no-reflow phenomenon, that the myocardial damage depends on the severity of microvascular damage and that prolonged ischemia time may increase the likelihood of "microvascular no-reflow phenomenon."

Aged↗

Technetium-99m-sestamibi uptake in axillary lymph node metastases in breast cancer patients.

In a prospective study the value of technetium-99m-sestamibi scintigraphy (MIBI scintigraphy) in staging axillary lymph node involvement in breast cancer patients was established. The study comprised 36 cases. The results of the staging were compared with physical and histological examination. MIBI scintigraphy had a sensitivity of 91% and a total accuracy of 81%. These percentages demonstrate the potential value of this technique; larger series will be needed to confirm our results.

Axilla↗

Technetium-99m-HmPAO brain SPECT in infantile Gaucher's disease.

The authors report serial technetium-99m hexamethylpropylene-amine-oxime brain single photon emission computed tomography (SPECT) findings in two infants with Gaucher's disease type 2. Detailed neurologic and laboratory examinations, including bone marrow biopsies and enzymatic assays, were described. Serial brain magnetic resonance imaging studies in one patient illustrated the progressive cerebral atrophy in the frontal and temporal lobes. The SPECT in both cases demonstrated positive findings of initial scattered hypoperfusion, with extending to hypoperfusion of the entire cerebrum after 4 months of clinical deterioration. These changes in the SPECT findings may reflect progressive degeneration of the cerebrum in Gaucher's disease type 2. Brain SPECT may provide useful information on cerebral flow and metabolic distribution corresponding to the neurologic deficits of neuronopathic Gaucher's disease.

Atrophy↗

Technetium-99m labelling of glycosylated somatostatin-14.

This study presents a technetium-99m labelling method based on organometallic chemistry. It describes the simple mixing of a 99mTc(I)-carbonyl compound [99mTc(OH2)3(CO)3]+ with a histidine-tagged somatostatin-dextran (SMS-Dx-His) conjugate. Somatostatin and histidine was coupled to periodate activated dextran. The linkage was stabilised by reductive amination. The conjugate was then radiolabelled with 99mTc by using the 99mTc(CO)3 core. The labelling efficiency was 65-80% and the radiochemical purity > 95%. In the in vitro cysteine challenge, the result showed that 25% of the radiolabel was released after 1 h incubation at 37 degrees C (cysteine-conjugate at 1000:1 molar ratio). The radiolabelled SMS-Dx-His showed similar HPLC profile as the unlabelled conjugate. This labelling method, employing non reducing conditions, is useful for the labelling of peptides containing disulphide bonds. It should be possible to be used also for labelling with rhenium-188 for therapeutic applications.

Chromatography, High Pressure Liquid↗

Stability studies on (99m)technetium(III) complexes with tridentate/monodentate thiol ligands and phosphine ('3 + 1 + 1' complexes).

The preparation and characterisation of 3 + 1 + 1 technetium complexes of the general formula [Tc(SES)(RS)(PMe2Ph)] (SES = tridentate dithiol ligand, E = S, O, NMe; RSH = monothiol ligand) at the n.c.a. level is described. The Tc(III) complexes are prepared in a one-step procedure starting from pertechnetate in yields of 85-95% of radiochemical purity. A comparison of their chromatographic data with the fully characterised 99Tc complexes indicate the identity of the investigated compounds. Stability studies show that the 99mTc complexes undergo some alteration in solution. They are oxidised to the 3 + 1 oxotechnetium (V) complexes and/or decompose in aqueous solution. In challenge experiments performed with glutathione, exchange of the monothiolato ligand occurs in the same manner as known for the 3 + 1 complexes.

Chromatography, High Pressure Liquid↗

The quantification of technetium in generator-derived pertechnetate using ICP-MS.

Previous analytical methods employed to measure 99Tc:99mTc ratios in chromatographic 99mTc generators, derived from fission-based 99Mo, were limited in monitoring the ratios in low activity generators, over the extent of their elution regimes. For regulatory purposes, ICP-MS was employed to measure total technetium in generator eluates down to a level of 200 pg ml(-1) (200 ppt). Measured 99Tc:99mTc ratios compared very well with the theoretically computed values, ranging from 47:1 for a first elution of a generator with a long ingrowth time to 1.4:1 for the 17th elution of a generator with a short ingrowth time.

Calibration↗

Technetium-99m labeling anti-amastigote polyclonal antibodies of Leishmania amazonensis.

Anti-amastigote polyclonal antibody (IgG) was incubated with solutions of stannous chloride and sodium borohidride. After that, 3.7 MBq of technetium-99m (99mTc) was added. A labeling yield of the antibody about 84% was obtained. After filtration of 99mTc-IgG, the radiochemical purity increased from 84 to 95%. The labeling of IgG with 99mTc did not modify the immunoreactivity of the antibody, since it was able to identify in vitro and in vivo the specific antigen of Leishmania amazonensis.

Animals↗

Anomalies in hepatobiliary excretion of technetium-99m-MAG3 preparations.

Technetium-99m-MAG3 is accepted as a renal tubular function agent. However, sporadic liver and gall bladder visualisation during its clinical use is clearly a disadvantage. HPLC-purified 99mTc-MAG3 samples exhibited appreciable hepatobiliary uptake (7%), and an elevated level of such uptake was observed in unpurified kit preparations, which was stated to be associated with the excretory property of the radiolabeled kit impurities. To verify this we attempted to quantitate the hepatobiliary uptake of the kit preparations with that of its radiolabeled components. The contribution of each component toward hepatobiliary uptake of the sample was calculated from their abundance in the chelate mixture and the individual biodistribution of the isolated components. However, the anticipated hepatobiliary uptake of different preparations of 99mTc-MAG3 calculated in this way was always lower than that of the experimental value determined directly. Further work is needed to explain the anomaly.

Animals↗

Rhenium-188 and technetium-99m nitridobis(N-ethoxy-N-ethyldithiocarbamate) leucocyte labelling radiopharmaceuticals: [188ReN(NOET)2] and [99mTcN(NOET)2], NOET = Et(EtO)NCS2: their in vitro localization and chemical behaviour.

In this study, we have investigated the preparation of rhenium-188 nitridobis(N-ethoxy-N-ethyldithiocarbamate) [188ReN(NOET)2] (NOET = Et(EtO)NCS2), analogous to the known technetium-99m radiopharmaceutical. The new 188Re complex was synthesized in good yield with a satisfactory radiochemical purity, using a kit method. The subcellular localization of both radiopharmaceuticals in granulocytes was observed by microautoradiography. The uptake was independent of the radionuclide and predominantly nuclear. Furthermore, HPLC was used to characterize the 99mTc complex before and after blood cell labelling and revealed that the intact radiopharmaceutical was involved.

Autoradiography↗

Determination of Sn(II) in technetium cold kits by voltammetry at the hanging mercury drop electrode (HMDE) and relevant radiopharmaceutical applications.

A novel approach for the determination of the stannous content in cold kits for labelling with 99mTc is described. The method is based on differential pulse polarography on the hanging mercury drop electrode in a methanol/water/perchloric acid mixture and is easy to perform. Examples for the determination of tin(II) in fractionated technetium cold kits are shown. The stability of tin(II) in solution was mainly dependent on the storage temperature and the kit composition. The low stability of stannous ions under certain conditions was shown to be the main reason for low radiochemical purity. Limits and dangers of fractionating kits are discussed and related to content and instability of tin(II).

Electrochemistry↗

99m-Technetium-labelled peptide-HYNIC conjugates: effects of lipophilicity and stability on biodistribution.

The aim of this study was to explore the effects of lipophilicity and stability on the biodistribution of 99mTc labelled peptides through the use of different co-ligands. 6-Hydrazinopyridine-3-carboxylic acid (HYNIC) was coupled to the somatostatin analogue RC160 and radiolabelled using a range of ethylendiaminediacetic acid (EDDA) and ethylenediaminetetraacetic acid (EDTA) derivatives as well as tricine and pyridine/tricine as co-ligands. After labelling with technetium-99m, chromatographic, stability, protein-binding, and rat biodistribution studies were performed. For most co-ligands, biodistribution correlated well with in vitro properties. Lipophilic substitution on EDDA resulted in higher protein binding, increased liver uptake, and intestinal excretion. Stabilisation of tricine with pyridines reduced blood levels and lowered liver uptake. EDTA derivatives showed high instability in vitro and in vivo.

Animals↗

The use of (99m)technetium-labeled MCP-1 to assess graft coronary artery disease in rat cardiac allografts.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is associated with the development of graft coronary artery disease (GCAD) following cardiac transplantation. This study assessed whether technetium 99m ((99m)Tc)-labeled MCP-1 binds its receptors in chronic cardiac transplants and thereby provides a potential modality to assess GCAD. METHODS: Allogeneic (PVG-->ACI, n = 9) and syngeneic (ACI-->ACI, n = 9) rat heterotopic heart transplants were performed. Allograft recipients were treated with 7.5 mg/kg per day of Cyclosporin A for 10 days until tolerance was achieved. After 90 days, animals were injected intravenously with (99m)Tc-MCP-1 and killed after 1 hour. Radioactivity of heart tissues was measured and standardized to uptake in the overall blood pool. Two-dimensional (99m)Tc-MCP-1 uptake (autoradiographs) was imaged by exposing 50-microm sections on a phosphoimager overnight. ED-1 staining of monocyte/macrophages was performed on serial sections. Additional sections were stained with elastin von Gieson and hematoxylin. Hearts were scored for luminal narrowing and intima/media ratio (I/M) with computerized image analysis. RESULTS: Allografts exhibited significantly more luminal narrowing (22.5 +/- 10.7% vs 2.6 +/- 4.6, p = 0.0005) and higher I/M (0.173 +/- 0.151 vs 0.015 +/- 0.029, p = 0.0088) than isografts. The ratio of (99m)Tc-MCP-1 uptake in allografts (1.04 +/- 0.4) was greater than that of isograft controls (0.72 +/- 0.11, p = 0.03). Pixel counts of autoradiographs and ED-1-stained sections demonstrated a modest correlation between the two (R(2) = 0.50). No significant differences were seen in acute rejection scores. CONCLUSION: (99m)Tc-MCP-1 uptake was higher in allografts vs isografts and was consistent with a greater degree of GCAD. These data demonstrating increased radiopharmaceutical uptake in hearts with GCAD provide a foundation for the development of a potentially non-invasive imaging assay of this disease process in heart transplantation.

Animals↗

Technetium 99m furifosmin regional myocardial uptake in patients with previous myocardial infarction: relation to thallium-201 activity and left ventricular function.

BACKGROUND: This study was designed to compare the results of rest-redistribution thallium-201 imaging with those of rest technetium 99m furifosmin single photon emission computed tomography in the same patients with chronic ischemic left ventricular (LV) dysfunction. METHODS: Twenty-one patients (mean age 62 +/- 9 years) with chronic myocardial infarction and LV dysfunction (mean LV ejection fraction 34% +/- 8%) underwent rest-redistribution thallium imaging and resting furifosmin single photon emission computed tomography on the same day. In each patient, regional thallium and furifosmin activity was quantitatively measured in 13 myocardial segments. Regional LV function was assessed in corresponding segments by echocardiography. RESULTS: At thallium imaging, 91 (33%) segments had normal uptake, 16 (6%) showed reversible defects, and the remaining 166 (61%) irreversible defects. Of these 166 irreversible defects, 74 (45%) had moderate (> or =58% of peak activity) and 92 (55%) severe (<58% of peak activity) reduction of thallium uptake. Regional furifosmin uptake was significantly related to both rest (r = 0.87, P < .0001) and redistribution (r = 0.90, P < .0001) thallium activity. Agreement in the evaluation of regional perfusion status between thallium and furifosmin imaging was observed in 70% of the 84 hypokinetic segments (kappa = 0.54) and in 76% of the 78 akinetic or dyskinetic segments (kappa = 0.60). Concordance in the detection of myocardial viability between thallium and furifosmin imaging was observed in 69 (82%) of hypokinetic regions (kappa = 0.60) and in 65 (83%) of akinetic or dyskinetic regions (kappa = 0.67). CONCLUSIONS: These results suggest that in patients with chronic coronary artery disease and LV dysfunction, quantitative rest-redistribution thallium scintigraphy and furifosmin tomography at rest provide similar results in the evaluation of perfusion status and in the detection of myocardial viability.

Aged↗

Repeatability of treadmill exercise ejection fraction and wall motion using technetium 99m-labeled sestamibi first-pass radionuclide ventriculography.

BACKGROUND: Peak treadmill exercise radionuclide ventriculography (RVG) with technetium 99m has recently been validated for determination of left ventricular ejection fraction (LVEF). However, the repeatability of this technique for determination of both LVEF and regional wall motion has not been reported. METHODS AND RESULTS: Each of 27 clinically stable patients underwent two treadmill exercise RVG studies within 40 +/- 51 days. The level of exercise achieved in the two tests was similar (double product: 26,357 +/- 3877 vs 26,621 +/- 4287), and there was no change in clinical or treatment status between the studies. Acquisition and processing were accomplished with a mobile multicrystal camera and a new version of a commercial software (Scinticor SIM 400 V. 4.1 BETA, Milwaukee, Wis.) that uses two left ventricular regions of interest. The two tests were compared to assess agreement (repeatability) on both an automatically calculated LVEF and wall motion in five left ventricular segments (basal anterior, distal anterior, apical, distal inferior, and basal inferior), with a 3-point semiquantitative visual score. Intraobserver and interobserver agreements (reproducibility) also were assessed on quantitative exercise LVEF derived from the same RVG test from a separate group of 20 patients with a broad range of exercise LVEF. The first and second treadmill exercise LVEFs were highly correlated (r = 0.92, SEE = 3.96, y = 0.97x + 0.58; and r = 0.99, SEE = 1.32, y = 0.99x + 0.25, respectively). Results of segmental visual score agreement between the first and the second treadmill first-pass studies were as follows: overall, 86% (116/135, kappa = 0.74); basal anterior, 85% (23/27, kappa = 0.72); distal anterior, 85% (23/27, kappa = 0.84); apical, 93% (25/27, kappa = 0.85); distal inferior, 93% (25/27, kappa = 0.80); and basal inferior, 67% (18/27, kappa = 0.64). CONCLUSION: Treadmill exercise first-pass RVG is a highly repeatable and reproducible test for quantitative LVEF and visual regional wall motion analysis. Our results imply the procedure may be useful for serial follow-up of patients with coronary artery disease and for the evaluation of the efficacy of medical or interventional treatment.

Adult↗

A Monte Carlo investigation of artifacts caused by liver uptake in single-photon emission computed tomography perfusion imaging with technetium 99m-labeled agents.

BACKGROUND: Significant hepatobiliary accumulation of technetium 99m-labeled cardiac perfusion agents has been shown to cause alterations in the apparent localization of the agents in the cardiac walls. A Monte Carlo study was conducted to investigate the hypothesis that the cardiac count changes are due to the inconsistencies in the projection data input to reconstruction, and that correction of the causes of these inconsistencies before reconstruction, or including knowledge of the physics underlying them in the reconstruction algorithm, would virtually eliminate these artifacts. METHODS AND RESULTS: The SIMIND Monte Carlo package was used to simulate 64 x 64 pixel projection images at 128 angles of the three-dimensional mathematical cardiac-torso (MCAT) phantom. Simulations were made of (1) a point source in the liver, (2) cardiac activity only, and (3) hepatic activity only. The planar projections and reconstructed point spread functions (PSFs) of the point source in the liver were investigated to study the nature of the inconsistencies introduced into the projections by imaging, and how these affect the distribution of counts in the reconstructed slices. Bull's eye polar maps of the counts at the center of the left ventricular wall of filtered back-projection (FBP) and maximum-likelihood expectation-maximization (MLEM) reconstructions of projections with solely cardiac activity, and with cardiac activity plus hepatic activity scaled to have twice the cardiac concentration, were compared to determine the magnitude and location of apparent changes in cardiac activity when hepatic activity is present. Separate simulations were made to allow the investigation of stationary spatial resolution, distance-dependent spatial resolution, attenuation, and scatter. The point source projections showed significant inconsistencies as a function of projection angle with the largest effect being caused by attenuation. When consistent projections were simulated, no significant impact of hepatic activity on cardiac counts was noted with FBP, or 100 iterations of MLEM. With inconsistent projections, reconstruction of 180 degrees resulted in greater apparent cardiac count losses than did 360 degrees reconstruction for both FBP and MLEM. The incorporation of attenuation correction in MLEM reconstruction reduced the changes in cardiac counts to that seen in simulations in which attenuation was not included, but resulted in increased apparent localization of activity in the posterior wall of the left ventricle when scatter was present in the simulated images. CONCLUSIONS: The apparent alterations in cardiac counts when significant hepatic localization is present is due to the inconsistency of the projections inherent in imaging. Prior correction of these, or accounting for them in the reconstruction algorithm, will virtually eliminate them as causes of artifactual changes in localization. Attenuation correction and scatter correction are both required to overcome the major sources of apparent count changes in the heart associated with hepatic uptake.

Artifacts↗

Attenuation-corrected rest thallium-201/stress technetium 99m sestamibi myocardial SPECT in normals.

BACKGROUND: Rest thallium-201/stress technetium 99m sestamibi protocol is widely used in the clinical setting. Although attenuation correction (AC) represents an important recent development in cardiac single photon emission computed tomography (SPECT) imaging, adjacent extracardiac activity can affect the myocardial count density distribution on AC images, particularly with 201Tl. The aims of this study were to compare normal distribution between AC rest 201Tl and stress 99mTc-sestamibi SPECT images as well as to evaluate the effect of extracardiac activity on AC SPECT images with 99mTc and 201Tl. METHODS AND RESULTS: A phantom measurement and a study of 21 patients with low likelihood of coronary artery disease were performed with a triple-head SPECT system equipped with a americium 241 line source. In the phantom study, the presence of extracardiac activity increased the inferior-to-anterior ratios, particularly with 201Tl (1.01 to 1.32). In the clinical data, reduced count density with 201Tl compared to 99mTc-sestamibi was observed in most of the noninferior segments. On an individual segment basis, 37 (20%) of 189 segments from 11 (52%) of 21 subjects showed reduced count density on the 201Tl image compared to 99mTc-sestamibi by >10% of peak activity. CONCLUSIONS: There is a significant difference in myocardial count density distribution between 99mTc-sestamibi and 201Tl on AC SPECT images, indicating that a careful image interpretation that considers the different normal count density distribution between the tracers and/or a tracer specific normal database is necessary, especially when defect reversibility is of concern. Further work should aim for the incorporation of scatter correction combined with attenuation correction.

Aged↗

Prognosis in patients with spontaneous chest pain, a nondiagnostic electrocardiogram, normal cardiac enzymes, and no evidence of severe resting ischemia by quantitative technetium 99m sestamibi tomographic imaging.

BACKGROUND: There are limited data addressing the outcome of patients with normal or near normal myocardial perfusion during chest pain at rest. The purpose of this study was to determine the prognosis of patients with spontaneous chest pain, a normal or nondiagnostic electrocardiogram, no enzymatic evidence of myocardial infarction, and no evidence of severe resting ischemia by quantitative technetium 99m (99mTc) sestamibi imaging. METHODS: In the study, 111 patients who fulfilled the above criteria were injected with 99mTc sestamibi during resting chest pain and were followed for a median 2.7 years. Of the patients in the study group, 58% had coronary artery disease that was documented by clinical history or coronary angiography. Tomographic 99mTc perfusion images were interpreted with a quantitative threshold technique initially developed to detect severely hypoperfused myocardium. The images were also interpreted qualitatively to detect patients with milder degrees of hypoperfused myocardium. RESULTS: During follow-up 3 patients had cardiac deaths, 5 had nonfatal myocardial infarctions, and 21 underwent revascularization procedures (13 within 3 months and 8 more than 3 months after the sestamibi study). At 3 years, survival free of cardiac death was 97%, survival free of cardiac death or myocardial infarction was 91%, and survival of cardiac death, myocardial infarction, or late revascularization was 82%. Quantitative analysis of the scans revealed that 100% of patients without fixed defects had 3-year survival free of cardiac death versus 76% of patients who had fixed defects (p < 0.001). Mild to moderate resting ischemia by qualitative interpretation of the scans was present in 20% of patients, but this did not predict outcome. CONCLUSIONS: Patients with spontaneous chest pain and nonischemic quantitative 99mTc sestamibi images were at reasonably low risk for hard cardiac events although some patients (18%) required revascularization.

Aged↗