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PubMed1992

Preoperative diagnosis of coronary artery disease in patients with valvular heart disease using technetium-99m isonitrile tomographic imaging together with high-dose dipyridamole and handgrip exercise.

Forty-seven consecutive patients (mean age 61 +/- 8 years) referred for cardiac catheterization due to moderate to severe aortic (n = 30) or mitral (n = 17) valvular heart disease were examined by technetium-99m isonitrile tomography together with a high-dose dipyridamole infusion (0.7 mg/kg) and handgrip stress. Tomography did not identify coronary artery disease (CAD) in 3 of the 21 patients with angiographically proven disease (sensitivity 86%) and suggested false positive results in 5 of the 26 without the disease (specificity 81% and negative predictive accuracy 88%). No patient without angina pectoris and with negative scintigraphy (n = 14) had angiographically significant (greater than or equal to 50% diameter stenosis) CAD. Overall vessel sensitivity was 63%, and specificity was 92%. The frequency of side effects during the dipyridamole-handgrip test was only 7%. No serious complications occurred during stress tests. Thus, technetium-99m isonitrile tomographic imaging, together with high-dose dipyridamole and handgrip exercise, is a useful noninvasive method in excluding significant CAD in patients with valvular heart disease.

Coronary Angiography↗
PubMed1988

Assessment of inflammatory bowel disease activity by technetium 99m phagocyte scanning.

Autologous technetium 99m-labeled phagocyte scanning has been used to assess disease activity in inflammatory bowel disease in 51 consecutive patients. Strong correlations were found between the 24-h fecal excretion of isotope and the histologic score of mucosal biopsy specimens (rS = 0.84, p less than 0.001, where rS is Spearman's rank correlation coefficient), and between the 24-h fecal excretion of isotope and a clinical inflammatory bowel disease activity index based on the Crohn's disease activity index (rS = 0.87, p less than 0.001). To develop a clinically useful and objective measure of inflammatory bowel disease activity that did not require a 24-h stool collection, the intensity of bowel uptake on scanning was graded visually from 0 to 4, a ratio of count rates for the region of interest to the iliac crest reference region was calculated, and the rapidity of labeled phagocyte uptake into inflamed bowel was measured as the peak uptake time. Visual grading of disease activity on the scans was validated by comparing it with the ratio of count rates from inflamed bowel regions of interest and those from the iliac crest reference region. The ratio of count rates showed a significant correlation with the clinical disease activity index (r = 0.75, p less than 0.001). The visual scan grade also correlated well with the clinical activity index (r = 0.87, p less than 0.001). Count rates from hourly scans were also used to calculate the time of peak uptake of counts for a given region of interest. There was a strong negative correlation between this peak uptake time and the fecal excretion of isotope (rS = -0.81, p less than 0.001), a clinical activity index (r = -0.60, p less than 0.001), and the histologic score of the mucosal biopsy specimens (r = -0.84, p less than 0.001). These results indicate that the technetium 99m-labeled phagocyte scan provides an objective assessment of disease activity in inflammatory bowel disease using the visual scan grade, ratio of count rates for the region of inflamed bowel, or by the peak uptake time, thereby avoiding the problems associated with fecal collections. This scanning test may prove to be of significant value in clinical management and in the assessment of treatment response.

Adolescent↗
PubMed1984

Technetium-99m benzimidazolyl iminodiacetic acid hepatobiliary radiopharmaceuticals: structure biodistribution studies.

The biodistribution of fifteen structural variants of the hepatobiliary radiopharmaceutical, technetium-99m benzimidazolyl iminodiacetic acid (BIMIDA) were determined 1 h after i.v. injection into rats. The best compounds with respect to hepatobiliary excretion were those with halogen substituents in the benzene ring of the BIMIDA ligand. The cholescintigraphic properties of the BIMIDA compounds compared favourably with those of technetium-99m acetanilido iminodiacetic acid (HIDA) radiopharmaceuticals.

Animals↗
PubMed1992

Measurement of myocardium at risk by technetium-99m sestamibi: correlation with coronary angiography.

Previous studies have shown that tomographic perfusion imaging with technetium-99m sestamibi (RP-30A) can accurately measure the myocardium at risk during acute myocardial infarction. The ability of coronary angiography to predict the wide variability in myocardium at risk was studied in 21 patients with their first acute myocardial infarction. In blinded fashion, two experienced angiographers provided an overall "best estimate" of the percent of left ventricular myocardium at risk considering multiple angiographic variables--infarct-related artery, location of stenosis (proximal or nonproximal), vessel diameter, length, territory and the number and size of proximal branches and collateral vessels. Many of these individual variables showed a significant association with myocardium at risk. The most important angiographic variable was the mean best estimate of the two angiographers (r = 0.89, p less than 0.0001). However, the SEE was large (8.6% of the left ventricle) and angiography significantly (p less than 0.002) overestimated myocardium at risk. When patients with an anterior or an inferior infarct were considered separately, the angiographic best estimate had a weaker correlation with myocardium at risk measured by technetium-99m sestamibi in patients in both groups (anterior infarction r = 0.65, p = 0.04; inferior infarction r = 0.65, p = 0.04. Seven patients with an inferior infarct and myocardium at risk ranging from 7% to 32% of the left ventricle had identical angiographic best estimates. Although angiographic estimates correlate closely with measurements of myocardium at risk in groups of patients, their ability to predict the myocardium at risk in individual patients is limited.

Adult↗
PubMed1992

Comparison of technetium-99m sestamibi and thallium-201 retention characteristics in canine myocardium.

OBJECTIVES: The aim of this study was to compare the myocardial retention of technetium-99m (Tc-99m) sestamibi and thallium-201 over a wide range of blood flow at different time points after tracer injection. BACKGROUND: Technetium-99m sestamibi has been proposed as a new perfusion tracer with better physical characteristics than those of thallium-201 for scintigraphic imaging. However, no studies have simultaneously compared the ability of both tracers to assess myocardial blood flow during pharmacologic vasodilation. METHODS: The myocardial retention of Tc-99m sestamibi and thallium-201 were compared over a wide range of blood flow induced by regional coronary occlusion and dipyridamole infusion in an open chest dog model. Myocardial retention of both tracers was determined by in vitro tissue counting at 2, 5, and 20 min after tracer injection and was correlated with microsphere-determined blood flow. RESULTS: Thallium-201 demonstrated greater absolute tissue retention than did Tc-99m sestamibi. At 2 min after tracer injection, there was an almost linear relation between the retention of both tracers and myocardial blood flow over a wide flow range. However, this relation was not maintained over time. At 20 min after injection, the retention of both tracers underestimated myocardial blood flow at higher flow rates. At 2, 5 and 20 min after injection, increments of relative tracer retention between the different levels of flow were always greater for thallium-201 than for Tc-99m sestamibi. CONCLUSIONS: Thallium-201 displays more suitable physiologic characteristics as a flow tracer and may allow better differentiation of myocardial regions with different levels of coronary flow reserve. For both tracers, early cardiac imaging may minimize underestimation of blood flow at higher flow rates.

Animals↗
PubMed1995

Incremental value of simultaneous assessment of myocardial function and perfusion with technetium-99m sestamibi for prediction of extent of coronary artery disease.

OBJECTIVES: This study assessed the incremental value of technetium-99m myocardial single-photon emission computed tomography (SPECT) and simultaneous first-pass radionuclide angiography, when added to treadmill exercise, for prediction of the extent of coronary artery disease. BACKGROUND: Technetium-99m count statistics permit the simultaneous assessment of myocardial perfusion and function. However, whether this characteristic improves prediction of the extent of coronary artery disease remains unknown. METHODS: We studied 70 consecutive patients who had coronary angiography within 6 months of the scintigraphic study. All patients underwent a symptom-limited treadmill exercise test. Treadmill data were summarized using a previously validated score. Left ventricular ejection fraction and regional wall motion were evaluated from a first-pass radionuclide angiogram acquired at peak treadmill exercise in the anterior view. Perfusion was assessed visually. Extent of angiographic disease was expressed as the presence or absence of multivessel disease (more than two coronary artery territories with > 50% stenosis) and as a score that reflects the location of severe (> 75%) stenosis. RESULTS: Stepwise addition of scintigraphic data (perfusion first, followed by function) to the treadmill score showed significant incremental value for prediction of the angiographic score at each step; exercise ejection fraction alone was the strongest independent predictor. Discriminant accuracy for detection of multivessel disease was also improved by the addition of perfusion information to the treadmill score and addition of regional wall motion analysis to both of them. In this case, ejection fraction failed to show independent value. CONCLUSIONS: The addition of simultaneously performed sestamibi perfusion SPECT and first-pass radionuclide angiography to the treadmill exercise test significantly improved prediction of the extent of coronary artery disease.

Coronary Angiography↗
PubMed1994

Influence of anatomic correction for transposition of the great arteries on myocardial perfusion: radionuclide imaging with technetium-99m 2-methoxy isobutyl isonitrile.

OBJECTIVES: We sought to determine the incidence of late perfusion defects attributable to coronary artery mobilization in patients undergoing anatomic correction for complete transposition of the great arteries. BACKGROUND: Anatomic correction (arterial switch procedure) is currently the surgical treatment of choice for complete transposition. From its conception, there has been concern about the impact on myocardial perfusion of the coronary artery mobilization and reimplantation involved in the correction. Previous studies have demonstrated myocardial perfusion defects in patients after correction, although a causal relation between coronary mobilization, and perfusion abnormality has not been established. METHODS: In a case-comparison study designed to test this hypothesis, 29 children underwent imaging with technetium-99m 2-methoxy isobutyl isonitrile (technetium-99m mibi). Ten had undergone anatomic correction (arterial switch group; interval from operation 6.9 +/- 1.42 years [range 4.9 to 9.1]); 9 had required noncoronary open heart surgery for other cardiac lesions (post-bypass group; interval from operation 5.6 +/- 3.6 years [range 1.0 to 13.25]); and 10 had had no surgical procedure (control group). The latter group comprised children with atrial or ventricular septal defects who required a radionuclide study for shunt calculation. Planar studies were performed in all 29 children, and additional tomographic acquisition was achieved in 25. To assess reversibility of perfusion defects both an exercise and a rest planar study were performed in the arterial switch group. RESULTS: Perfusion abnormalities were observed in seven of the nine children in the postbypass group and in all 10 children in the arterial switch group. The frequency of perfusion defects in these two groups was similar, with at least 25% of the tomographic segments reported being abnormal. The control group had significantly fewer defects than the other two groups (p = 0.02), with only 8% of the tomographic segments judged to be abnormal. In all except one patient in the arterial switch group, the segments reported as abnormal on the planar exercise study were either abnormal or equivocal on the rest study, indicating a fixed abnormality. CONCLUSIONS: Although the precise etiology of these perfusion abnormalities cannot be defined from this study, these data suggest that their origin is related more to the insult of open heart surgery itself than to the coronary manipulation involved in the arterial switch procedure. The functional importance requires further study.

Cardiac Surgical Procedures↗
PubMed1994

How accurate is dobutamine stress electrocardiography for detection of coronary artery disease? Comparison with two-dimensional echocardiography and technetium-99m methoxyl isobutyl isonitrile (mibi) perfusion scintigraphy.

OBJECTIVES: This study was designed to establish the appropriate diagnostic criteria for positive dobutamine electrocardiographic (ECG) stress test results and to compare their accuracy with those of dobutamine two-dimensional echocardiography and perfusion scintigraphy. BACKGROUND: Conventional criteria for positive findings on ECG exercise testing may not be appropriate for use with dobutamine ECG stress testing. METHODS: One hundred twenty-nine consecutive patients with an interpretable ECG and without previous myocardial infarction were prospectively studied at the time of coronary arteriography. All completed a standard dobutamine protocol (5 to 40 micrograms/kg body weight per min in 3-min dose increments) without side effects. Significant coronary artery disease, defined as > 50% lumen diameter stenosis of a major epicardial coronary artery on coronary angiography, was present in 83 patients. Empiric receiver operating curves were generated for various ECG criteria derived from computer-averaged signals. RESULTS: The best ECG criterion, with a sensitivity of 42% and a specificity of 83%, was an ST segment shift, relative to baseline, of 0.5 mm 80 ms after the J point. The sensitivity of this criterion was greater than that of the conventional criterion of 1-mm ST segment depression 60 (23%) or 80 (18%) ms after the J point, was comparable to that of chest pain occurring during the test (44%, p = NS) but remained inferior to the sensitivities of technetium-99m methoxyl isobutyl isonitrile (mibi) perfusion (76%) or stress echocardiography (76%, p < 0.001, for both). The specificity of this criterion was not significantly different from that of technetium-99m mibi perfusion tomography (65%) or stress echocardiography (89%) but was superior to that of chest pain (59%, p < 0.025). CONCLUSIONS: We conclude that this new criterion for dobutamine electrocardiography is specific but that an imaging technique is still required to accurately predict coronary artery disease.

Adult↗
PubMed1987

Brain imaging agents: synthesis and characterization of (N-piperidinylethyl) hexamethyl diaminodithiolate oxo technetium(V) complexes.

Two 99mTc complexes of (N-piperidinylethyl) hexamethyl diaminodithiol (NEP-DADT) have shown high brain uptake in rodents and lower primates. One of these 99mTc complexes has given positive images of the brain in man which are qualitatively related to regional brain blood flow (rCBF). In order to determine the structure of these 99mTc products, the corresponding 99Tc(NEP-DADT) complexes were prepared and characterized by HPLC, TLC, fast-atom-bombardment mass spectrometry (FAB MS) and other analytical techniques. These results indicate that the two 99Tc (NEP-DADT) complexes are syn and anti isomers (i.e. one isomer has the N-piperdinylethyl side chain located syn to the technetium oxo core while the other has this side chain located anti to the technetium oxo core).

Brain↗
PubMed1988

A formate based precursor for the preparation of technetium complexes.

Tc-formate complexes have been prepared by electrolytic, stannous, and borohydride reduction of pertechnetate in formate buffer. Individual Tc-formate complexes were isolated from reaction mixtures with silica bonded phase anion-exchange HPLC. The predominate air stable red Tc-formate complex has a negative charge, an absorption maximum at 536 nm, and a molecular weight between 100 and 300 dalton. The isolated major Tc-formate complex was found to react with isocyanide, diphosphonate, and various nitrogenous ligands. The relevant use of Tc-formate complexes as synthetic precursors to other technetium complexes is seen as being beneficial to the understanding of technetium ligand substitution.

Chemical Phenomena↗
PubMed1989

Synthesis and biological properties of the lipophilic technetium-99m complex 99mTc(acac)3.

In the development of technetium-99m radiopharmaceuticals for the evaluation of regional cerebral perfusion, one series of complexes that has remained unexplored is the neutral lipophilic tris complexes formed with beta-diketonato ligands. The prototype complex of this series, tris(2,4-pentanedionato) technetium(III), has been prepared via a new synthetic route and chemically characterized using 99Tc and the biodistribution of the no-carrier-added 99mTc complex has been determined. The 99mTc complex was found to be distributed throughout the body with persistent high blood levels indicative of a high degree of protein binding. The primary route of excretion was the hepatobiliary system as indicated by the appearance of 99mTc in the gut and feces at longer sample times post-injection. Although this complex was not retained by the brain, it does provide a starting point from which a more effective agent might be developed.

Animals↗
PubMed1991

Chloro----hydroxy substitution on technetium BATO [TcCl(dioxime)3 BR] complexes.

The neutral, seven coordinate complexes of technetium known as the BATO (Boronic acid Adducts of Technetium diOximes) complexes have shown their utility as myocardial and cerebral perfusion agents. The axial chloride ligand of the BATO complexes [99mTcCl(dioxime)3 BR] is labile to substitution by a competitive anion; under physiological conditions, the axial chloride ligand can be replaced by a hydroxy group. The chloro and hydroxy analogs have different biodistributions and single-pass cerebral extraction efficiencies. The influence of structure on the rate of the in vitro chloro/hydroxy exchange process has been studied. The mechanism of axial ligand exchange was found to be SN1-CB, which proceeds by way of a transient, neutral six coordinate complex. Evidence is presented which indicates that chloro/hydroxy exchange is not the mechanism by which BATO complexes are retained in the brain.

Animals↗
PubMed1993

CEA-immunoscintigraphy with 99m-technetium correlates with tumour cell differentiation in colorectal cancer.

The clinical usefulness of immunoscintigraphy with the monoclonal anti-CEA (carcinoembryonic antigen) antibody BW431/26, directly labelled with 99m-Technetium in targeting colorectal carcinomas was investigated in 43 patients. In addition, tumour cell grading and CEA-expression were examined immunohistochemically. Best imaging results were obtained in pelvic tumour lesions (sensitivity 80%). Tumour grading correlated with radioimmunoimaging, well differentiated tumours being detectable at a higher rate (P = 0.09). Immunoscintigraphy preceded the findings of conventional diagnostic methods in 3 patients. In 4 cases immunoscintigraphy was decisive for patients management. Therefore, immunoscintigraphy with 99m-Technetium is valuable in directing patients management if conventional diagnostic methods remain undecisive.

Adult↗
PubMed1993

A new method of technetium-99m labeling of monoclonal antibodies through sugar residues. A study with TAG-72 specific CC-49 antibody.

We have developed a very efficient labeling technique for monoclonal antibodies with technetium-99m. Oxidation of sugar residues on the IgG class of antibodies leads to the generation of aldehyde groups which are further reacted with two newly developed hydrazide compounds. This methodology introduces sulfhydryl groups on the antibody through sugar residues which can be labeled with technetium-99m. We have studied the TAG-72 specific second generation antibody CC-49. The specific activity of the labeled antibody was high without loss of its immunoreactivity.

Adenocarcinoma↗
PubMed1994

In vivo metabolism of the technetium isonitrile complex [Tc(2-ethoxy-2-methyl-1-isocyanopropane)6]+.

Technetium(2-ethoxy-2-methyl-1-isocyanopropane)6+, [Tc-EIBT] is a complex of technetium(I) structurally similar but slightly more lipophilic than the commercial myocardial perfusion agent Cardiolite [Tc-MIBI]. Tc-EIBI exhibits rapid extraction from the blood into heart, liver, kidney and striated muscle and rapid hepatobiliary clearance. In the guinea pig, unlike Tc-MIBI, this compound is almost completely enzymatically metabolized to numerous cationic complexes containing a mixture of ethyl other and hydroxy isonitrile ligands. Substitution of the ethyl other group for a methyl ether produces an agent that shows selective in vivo metabolism and more rapid clearance from the liver.

Animals↗
PubMed1996

Technetium labeling of bi, tri and tetradentate ligands derived from 2-aminocyclopentene-1-dithiocarboxylic acid: characterization and biodistribution of their oxo and nitrido 99mtechnetium complexes.

We have synthesized and characterized seven ligands derived from 2-aminocyclopentene-1-dithiocarboxylic acid with different donor sets (SN2-, SNO2-, SNN2-, SNNO3- and SNNN3-) and different substituents on the sulfur moieties-SR (with R = H, CH3 or C2H5O(CH3)CH). With five of these ligands technetium nitrido complexes have been obtained with high yields (over 95%) using rather harsh conditions (pH = 1, temperature > or = 80 degrees C), whereas for technetium oxo complexes similar high yields were only obtained with two ligands but with mild conditions (pH = 7-8, temperature approximately equal to 50 degrees C). Changing an OH group for an NH2 has a drastic effect upon labeling yields. The possibility of complexing ligands as either oxo (TcO)3+ or nitrido (TcN)2+ derivatives increases the number of available labeled agents with different overall change and consequently with different biological behavior.

Animals↗
PubMed2004

Differential prognostic significance of peri-infarction versus remote myocardial ischemia on stress technetium-99m sestamibi tomography in patients with healed myocardial infarction.

Peri-infarction and remote myocardial ischemia involve different myocardial substrates, but their differential clinical implications have not been previously studied. We assessed the differential prognostic significance of peri-infarction and remote ischemia during long-term follow-up in patients with healed myocardial infarction. We studied 345 patients (59 +/- 12 years old; 282 men) with previous myocardial infarction who demonstrated reversible perfusion abnormalities on exercise or dobutamine stress technetium-99m sestamibi tomography. Follow-up events for 5.5 +/- 2.6 years were 60 deaths (17%; 40 cardiac deaths) and 25 reinfarctions (7%). Reversible perfusion abnormalities were detected in the remote region in 129 patients (37%), the peri-infarction region in 142 patients (41%), and in both regions in 74 patients (21%). The annual rates of cardiac death in these groups were 1.2%, 2.8%, and 2.9%, respectively (p <0.01). The annual rates of reinfarction were 1%, 1.5%, and 0.9%, respectively (p = NS). In a multivariate analysis model, independent predictors of cardiac death were history of heart failure (risk ratio [RR] 2.8, 95% confidence interval [95% CI] 1.2 to 7), diabetes mellitus (RR 4.1, 95% CI 1.9 to 8.9), summed score at rest (RR 1.4, 95% CI 1.1 to 3.1), and peri-infarction ischemia (RR 2.6, 95% CI 1.1 to 6.1). Predictors of reinfarction were age (RR 1.03, 95% CI 1.01 to 1.07) and diabetes mellitus (RR 3.3, 95% CI 1.2 to 9.1). Peri-infarction ischemia assessed by stress technetium-99m sestamibi tomography is associated with a greater risk of cardiac death than is remote ischemia. The risk of reinfarction is not related to the location of ischemia.

Aged↗
PubMed2006

Vascularity of the femoral head after Birmingham hip resurfacing. A technetium Tc 99m bone scan/single photon emission computed tomography study.

To investigate the vascularity of femoral heads after Birmingham hip resurfacing (BHR), we used a visual scale to assess technetium Tc 99m HDP planar and single photon emission computed tomography bone scans of 36 arthroplasties in 32 asymptomatic patients for an average of 26 months after BHR. The validity of this method was demonstrated by comparing levels of radiation detected from within and immediately adjacent to a BHR prosthesis placed on a technetium Tc 99m radioisotope tracer-filled hollow tube and further validated in vivo by comparing radiation levels from bilateral hip scans in human subjects with 2 normal hips and with unilateral BHR. All femoral heads scanned postoperatively appeared vascular. We speculate that preserved femoral head vascularity after BHR may be related to increased intraosseous blood supply from metaphyseal vessels in arthritic hips.

Arthroplasty, Replacement, Hip↗