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PubMed1991

Technetium-99m-labeled monoclonal antibodies for immunoscintigraphy. Simplified preparation and evaluation.

Ascorbic acid incubated with monoclonal antibodies (22 degrees C, 60 min, pH 6.5) at a molar ratio of 3500:1, reduced 2.7 +/- 0.2% of the available disulfides to sulfhydryl groups that strongly bind 99mTc, and provided greater than 95% labeling efficiency for several IgM, IgG and F(ab')2 antibodies. The colloid formation was consistently less than 3% and the stability of the tracer when challenged with DTPA and cysteine was excellent. The immunospecificity of labeled antibodies as determined by immobilized specific antigen assay was 84 +/- 1% for IgM and 82.6 +/- 1.1% for IgG antibodies. For in vivo evaluation in mice bearing experimental abscesses and tumors, corresponding 125I-labeled antibodies served as controls. The liver uptake was similar (P = 0.76 and P = 0.12) for 99mTc or 125I labeled antinuclear antibody TNT-1 in mice bearing abscesses as well as for 99mTc-TNT-1-F(ab')2 and 125I-TNT-1-F(ab')2 in mice bearing tumors. Higher but statistically insignificant (P = 0.08, 0.18, and 0.73) urinary excretion was noted for 99mTc-antibodies. For corresponding 99mTc- and 125I-labeled antibodies, the abscess to muscle ratios (3.3 +/- 0.5 vs. 3.4 +/- 0.8) and tumor to muscle ratios (10.04 +/- 4.4 vs. 10.54 +/- 3.0) were similar. The high 99mTc-TNT-1-F(ab')2 uptake permitted excellent scintigraphic visualization of tumors whereas the nonspecific 99mTc-HSA did not (tumor/muscle ratio: 2.4 +/- 0.3). This method is simple, reliable, and adaptable to an instant labeling technique.

Animals↗

PubMed1997

Technetium-99m-meso-HMPAO as a potential agent to image cerebral glutathione content.

UNLABELLED: To clarify whether the content of glutathione (GSH) in the brain can be estimated by the uptake of 99mTc-meso-HMPAO, we conducted the following in vivo and in vitro experiments. METHODS: We investigated the effect of diethyl maleate (DEM) and buthionine sulfoximine (BSO) administration on the brain uptake of 99mTc-meso-HMPAO in the mouse, rat and rabbit, and the chemical specificity of in vitro interaction of 99mTc-HMPAO to GSH using measurements of octanol-extractable radioactivity as an index of remaining intact tracer. RESULTS: The uptake of 99mTc-meso-HMPAO in the mouse and rat brain were reduced together with decreased content of GSH by preloading of DEM, a GSH depletor that acts through glutathione S-transferase. Neither 99mTc-meso-HMPAO uptake nor GSH content was affected in the rabbit brain. Similarly, the uptake of 99mTc-meso-HMPAO and GSH content in the mouse brain was reduced by preinjection of BSO, a GSH depletor that acts through gamma-glutamylcysteine synthetase. In an in vitro study, 99mTc-HMPAO showed reactivity to the molecules possessing a -SH group, but were not specific to GSH. The order of 99mTc-meso-HMPAO reactivity to the mouse brain homogenate agreed with the order of GSH concentration: normal > BSO > DEM. GSH was a major contributor to the conversion reaction of 99mTc-meso-HMPAO to hydrophilic complex in mouse brain homogenate. CONCLUSION: GSH may have a major responsibility for trapping 99mTc-HMPAO in the brain, suggesting the possibility of in vivo measurement of brain GSH with 99mTc-meso-HMPAO.

Animals↗

PubMed1994

Investigations of ascorbate for direct labeling of antibodies with technetium-99m.

UNLABELLED: Recently, a method for the direct labeling of antibodies with 99mTc was described in which sulfhydryls were reportedly generated by reduction of antibody disulfides with ascorbic acid. Thereafter, these proteins may be labeled at high efficiency with 99mTc following reduction of pertechnetate with dithionite. This investigation was initially conducted to evaluate the mechanism of the increased stability towards cysteine challenge reported for the label and subsequently to determine the role of ascorbate in the labeling process. METHODS: It was possible to reproduce the reported high labeling efficiencies by increasing the dithionite concentration fivefold, presumably because of variabilities among lots of commercial sodium dithionite. RESULTS: Despite success in labeling, it was not possible to confirm that antibody reduction followed the treatment with ascorbate. Using both Ellman's reagent and 2,2' dithiodipyridine as indicators, we were unable to detect sulfhydryls on one IgG antibody treated at ten times the suggested ascorbate-to-antibody molar ratio. It was estimated that the number of sulfhydryls generated could not have been more than 1% (dithiodipyridine) to 2% (Ellman's). Furthermore, radiolabeling efficiencies for two IgG antibodies and stabilities of the label to cysteine challenge were unchanged when the ascorbate was eliminated. The number of sulfhydryls generated by treatment of the antibody with dithionite at 1-2 times the concentration required for adequate labeling was about 1% (dithiodipyridine) to 5% (Ellman's). CONCLUSION: For the conditions of this investigation and for the antibodies employed, ascorbate apparently played no more than a minor role at best in the labeling process. If antibody reduction occurred, this most likely was a result of residual dithionite presented to the protein along with the reduced 99mTc.

Antibodies↗

PubMed2005

Design and synthesis of site directed maleimide bifunctional chelators for technetium and rhenium.

A new family of heterobifunctional linkers (L1-L9) containing a terminus consisting of a tridentate donor set for coordination of the {M(CO)(3)}(+) core (M = Tc, Re), and a thiol reactive maleimide group has been prepared conveniently and in high yield under Mitsunobu reaction conditions by the coupling of an appropriate alcohol derivative with maleimide. The rhenium complexes [Re(CO)(3)(Lx)]Br (x= 1-9) were prepared in good yields from the reactions of the ligands and (NEt(4))(2)[Re(CO)(3)Br(3)] in refluxing methanol. The ligands and their Re complexes were characterized by (1)H and (13)C NMR, IR, and ESI-MS. Ligand L4 and [Re(CO)(3)(L5)]Br have been structurally characterized by X-ray crystallography. Photoexcitation of solutions of the complexes [Re(CO)(3)(Lx)]Br (x= 4-6) gives rise to intense and prolonged luminescence at room temperature (fluorescence lifetimes of ca. 16 micros). The ligands and their Re complexes react smoothly at the maleimide linker with sulfhydryl groups of peptides and proteins at room temperature in phosphate-buffered saline (PBS, pH 7.4) to form stable thioether bioconjugates. The photoluminescence properties of the labeled conjugates are similar to those of the parent complexes, but with even longer lifetimes. The ligands can also be labeled at room temperature with (99m)Tc to give chemically robust complexes. The corresponding hydrazinonicotinamide derivative N-[5-(6'-hydrazinopyridine-3'-carbonyl)aminopentyl]maleimide (L10) was also prepared. While coupling of L10 to cysteine ethylester and synthesis of the rhenium derivative [ReCl(3)(HYNIC-maleimide)(2)] were successfully accomplished, attempts to couple [ReCl(3)(HYNIC-maleimide)(2)] to glutathione or BSA yielded intractable mixtures.

Chelating Agents↗

PubMed1994

Tridentate ligands containing the SNS donor atom set as a novel backbone for the development of technetium brain-imaging agents.

In developing 99mTc complexes as potential brain-imaging agents, we investigated the coordination chemistry of ligands containing sulfur and nitrogen donor atoms with the general formula R-CH2CH2N(CH2CH2SH)2 (R = C2H5S, (C2H5)2N). These ligands act as tridentate SNS chelates to the TcO3+ core, leaving open one coordination site cis to the oxo group. In reactions with the highly reactive [99TcOCl4]- precursor, this vacancy was occupied by a chlorine atom. When the ligands reacted in the presence of 4-methoxythiophenol, using 99Tc(V)-gluconate as precursor, the vacancy was filled with 4-methoxythiophenol, which acted as coligand. Thus neutral mixed ligand complexes of the general formula [TcO((SCH2CH2)2NCH2CH2R)X], where X = Cl or 4-methoxythiophenol, were synthesized. The complexes were characterized by UV-vis, IR, 1H NMR, crystallographic, and elemental analyses. The crystal structures of 3a (R = C2H5S, X = Cl) and 4b (R = (C2H5)2N, X = 4-methoxythiophenol) demonstrated that the coordination geometry is trigonal bipyramidal with the N1 and Cl or S3 occupying the apical positions and the basal plane defined by the S1 and S2 of the tridentate ligand and the oxo group. The complexes 4a(99mTc) (R = C2H5S, X = 4-methoxythiophenol) and 4b(99mTc) were prepared using 99mTc-glucoheptonate as precursor and were purified by HPLC. Biodistribution in mice showed high initial brain uptake (3.68% and 3.56% dose/organ for 4a(99mTc) and 4b(99m-Tc), respectively). Complex 4b(99mTc) displayed significantly higher brain/blood values and prolonged retention in brain as well. The results suggest that structural modifications based on configurations 4a,b may provide novel 99mTc brain-imaging agents with improved biological characteristics.

Animals↗

PubMed1987

Serum stability and non-specific binding of technetium-99m labeled diaminodithiol for protein labeling.

Previously we investigated the use of DTPA-coupled proteins to simplify labeling with 99mTc but especially to improve the stability of the label. These investigations have now been extended to include several N2S2 ligands such as N,N'-bis(2-methyl-2-mercaptopropyl)ethylenediamine (DADT) and a novel ligand of similar structure with a propylene bridge between two amines, 2-hydroxy-N,N'-bis(2-methyl-2-mercaptopropyl)propylenediamine++ + (DADT-3C-2OH). The condition of labeling of free ligand (pH, buffer and tin concentration) was optimized to provide 100% chelation with 99mTc at reasonable ligand concentrations (100 micrograms/mL or less). Labeling was determined by paper chromatography, reverse-phase and size-exclusion HPLC. After incubation in fresh serum, 37 degrees C for 24 h, repeat analysis showed less than 5% dissociation of the chelate. By contrast, the DTPA chelate shows instability towards oxidation during this period. DADT derivatized on an ethylene carbon showed almost identical serum stability as DADT itself whereas when derivatized on a nitrogen greater instabilities were apparent. Using identical labeling conditions, free DADT was chelated in the presence of IgG at different ligand: protein molar ratios. Non-specific binding of 99mTc to IgG at a 10:1 DADT-HM:IgG molar ratio was as little as 5% and was essentially zero at a 2:1 DADT:IgG molar ratio when labeling was by transcomplexation from 99mTc-EDTA. The DADT-3C-2OH ligand showed superior performance both in regard to serum stability and the absence of non-specific binding. In conclusion, the N2S2 ligands form more stable chelates with 99mTc than does DTPA with reduced non-specific binding and may therefore represent an attractive alternative for labeling proteins with 99mTc by the bifunctional chelate approach.

Amines↗

PubMed1976

[Study on tumor affinity of technetium-99m-labeled radiopharmaceuticals. (2) 99mTc-Sn-diphosphonate (99mTc-EHDP), 99mTc-Sn-dimercaptosuccinic acid (99mTc-DMSA), and 99mTc-Sn-diethyl stilbestrol diphosphate (99mTc-DSDP)].

The authors have examined the tumor affinity of various 99mTc-labelled radiopharmaceuticals to Ehrlich's tumor for the purpose of delineating positively human malignant neoplasm. This paper includes biologic distributions of 99mTc-Sn-diphosphonate (99mTc-EHDP), 99mTc-Sn-dimercaptosuccinic acid (99mTc-DMSA) and 99mTc-Sn-diethyl stilbestrol diphosphate (99mTc-DSDP, 99mTc-Honvan) as the second report on the tumor affinity to the Ehrlich-bearing mice. (a) Tumor concentration of 99mTc-EHDP was lowest and the positive delineation of implanted tumor with 99mTc-EHDP was poorest in sequential images, though the active accumulation to some soft tissue maglinant neoplasms, the breast cancer and the thyroid cancer, has been reported. (b) Tumor concentration and tumor to blood ratio of 99mTc-DMSA were not so high on the contrary of our expectation that 197Hg-DMSA may show the high tumor concentration and the high tumor to blood ratio like 197Hg chlormerodrin as same renal scanning radiopharmaceuticals. (c) Tumor concentration of 99mTc-DSDP was highest. Tumor to blood concentration ratio, however, was lower than that of the above mentioned radiopharmaceuticals but tumor to liver ratio and/or tumor to lung ratio was over 1.0 at the earlier time. Biologic distribution of 99mTc-DSDP was similar to that of 32P labeled DSDP and then it is presumed that 99mTc is labeled at phosphate ester of DSDP which is dephospholytated immediately by phospholylase in vivo following the intravenous injection. Therefore, it may be assumed that the accumulation mechanism of 99mTc-DSDP to Ehrlich's tumor is related to the phospholylase activity in neoplasms but is not known precisely.

Animals↗

PubMedDate not supplied

Synthesis, characterization, and biological evaluation of neutral nitrido technetium(V) mixed ligand complexes containing dithiolates and aminodiphosphines. A novel system for linking technetium to biomolecules.

A new biomolecule labeling method that utilizes the [(99m)Tc(N)(PNP)](2+) metal fragment is presented. Thus, a series of nitrido mixed-ligand M(V) complexes (M = (99m)Tc, (99g)Tc, Re), [M(N)(Ln)(PNP)], where Ln is the dianionic form of a dithiolate or substituted-dithiolate ligand and PNP is an aminodiphosphine, is described. (99m)Tc complexes can be prepared using either a two-step or a three-step procedure starting from generator-eluted pertechnetate through a prereduced mixture of [(99m)Tc(N)]-containing species, followed by sequential or contemporary addition of the relevant dithiolate and aminodiphosphine. The reactions of 2,3-dimercaptopropionic acid (H(2)L1) with [Tc(N)(PNP)](2+) were investigated in detail. It was found that this bidentate ligand coordinated the metal fragment through the [S(-),S(-)] donor atom pair, to yield neutral mixed-ligand complexes [(99m)Tc(N)(L1)(PNP)] in high specific activity. The additional carboxylic functional group was not involved in metal coordination, thus remaining available for conjugation to target-specific molecules. Dithiolates incorporating pendant functional group(s) gave rise to a 1:1 diastereoisomeric mixture of syn-[M(N)(Ln)(PNP)] and anti-[M(N)(Ln)(PNP)] derivatives, depending on the relative orientation of the dithiolate substituent(s) with respect to the terminal nitrido group, and no isomeric conversion was detected. (99m)Tc species had been proven to be identical with the (99g)Tc complexes prepared at the macroscopic level by comparison of the corresponding radiometric and UV/vis HPLC profiles. Challenge experiments with cysteine or glutathione indicated that these physiological agents had no effect on the stability of this class of mixed-ligand (99m)Tc-complexes. Biodistribution studies in rats of selected (99m)Tc-complexes showed a rapid clearance from the blood and tissues after 60 min pi.

Animals↗

PubMed1992

Evaluation of changes in myocardial function on exercise in patients with coronary artery disease using gated MIBI scintigraphy.

Technetium-99m-methoxy-isobutyl-isonitrile (MIBI) is a myocardial perfusion agent which allows simultaneous assessment of left ventricular function. We evaluated left ventricular (LV) function with exercise using a new method of myocardial profiling in 43 patients with chest pain. Twenty-eight had significant coronary artery disease and 15 were normal on coronary angiography. Results were compared to equilibrium radionuclide ventriculography. MIBI fractional shortening (FS) correlated well with ejection fraction (EF) on exercise (r = 0.79, P = less than 0.001). There was also a good correlation between changes in global function from rest to exercise (r = 0.82, P = less than 0.001) with a sensitivity of diagnosing CAD of 71% and specificity of 80%. New regional wall abnormalities were detected in 25/28 with CAD with a sensitivity of 89% and specificity of 60%. There was also a close correlation between mean diameters measured with gated MIBI scans and volumes measured with RNV, end-diastolic diameter (EDD) versus end-diastolic volume (EDV) r = 0.78 (P = less than 0.001) at rest and r = 0.74 (P = less than 0.001) on exercise and end-systolic diameter (ESD) versus end-systolic volume (ESV) r = 0.72 (P = less than 0.001) at rest and r = 0.72 (P = less than 0.001) on exercise. This produced a sensitivity for detecting CAD of 79% and a specificity of 73%. These results show that gated MIBI scanning on exercise provides information comparable to RNV so enhancing the diagnostic usefulness of MIBI.

Adult↗

PubMed1998

Human polyclonal immunoglobulin labelled with technetium-99m via NHS-MAG3: a comparison of radiochemical behavior and biological efficacy with other labelling methods.

The aim of this study was to evaluate the radiochemical behavior, biological distribution, and localization in infection sites in mice of a human polyclonal immunoglobulin (HIG) labelled with 99mTc by a novel MAG3-labelling method. The resulting [99mTc]MAG3-HIG was compared with [99mTc]HIG preparations radiolabelled directly via 2-mercaptoethanol (2-Me) or stannous ion (Sn) reduction and indirectly via 2-iminothiolane (2-Im) conjugation. All preparations showed similar UV and radioactivity HPLC profile to that of native HIG except for 2-Im-HIG, which showed aggregates. The stabilities of the label to challenge with cysteine were similar for all the preparations. By nondenaturing SDS-PAGE, all preparations other than MAG3-HIG showed evidence of lower molecular weight fragments. The tissue distribution 4 and 24 h after intravenous administration of the four preparations were compared in mice previously administered with an isolate of Staphylococcus aureus in one thigh. The pharmacokinetics varied among the different preparations. When prepared via 2-Me, Sn, and 2-Im, both blood clearance and urinary excretion were faster than that of labelled MAG3-HIG. The absolute uptake in the infected thigh at 24 h was significantly higher for HIG labelled via MAG3 and 2-Me vs. the remaining methods. The infected thigh/normal thigh radioactivity ratios were similar at both time points for labelled HIG prepared via 2-Me, 2-Im, and NHS-MAG, methods but was significantly lower at 24 h for HIG prepared via Sn. The radioactive HPLC profiles of serum at 4 and 24 h were similar to that of the radiolabelled injectates. Based on these data we conclude that each radiolabelled HIG preparation studied showed increased localization in infectious foci although [99Tc]MAG3-HIG showed superior radiochemical and biological characteristics under the conditions of this investigation.

Animals↗

PubMed1990

In vitro validation of a simple tomographic technique for estimation of percentage myocardium at risk using methoxyisobutyl isonitrile technetium 99m (sestamibi).

With the advent of technetium 99m-labeled myocardial blood flow agents, there is a need for a simple technique for quantitation of infarcted or jeopardized myocardium (IM). This study provides an in vitro validation of a simple technique based upon the analysis of three short-axis slices through the heart following emission computed tomography. All acquisitions were performed using a static cardiac phantom containing pertechnetate Tc 99m. Activity in the phantom was adjusted so that the count density and myocardial-to-background ratio were comparable to those observed in patients. Plastic insets (range of sizes = 4%-72% of myocardium) were used to simulate transmural infarctions. Eighteen studies were acquired, each over 180 degrees into a 64 x 64 matrix. Data were reconstructed using a Ramp Hanning filter with cut off at 0.7 times the Nyquist frequency. Short-axis slices of the myocardium were then generated, and representative apical (A), mid-ventricular (MV), and basal (B) slices were selected. For each slice, a circumferential profile was generated, and the average radius (R) was measured. The fraction (F) of the profile falling below a threshold value was considered to represent IM. Total IM was given by % IM = 100 x (RB FB + RMV FMV + 0.67 RA FA)/(RB + RMV + 0.67 RA), where the subscripts to R and F refer to the relevant short-axis slices. For a threshold set at 60% of peak, measured IM agreed closely with true IM (R2 = 0.98, measured IM = 1.01 x true IM - 1.35). Measurement of % IM was not distorted by variations in slice radius or in slice selection.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1992

Effect of coronary reperfusion on technetium-99m methoxyisobutylisonitrile uptake by viable and necrotic myocardium in the dog.

Technetium-99m hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) distribution is flow-dependent, permitting the imaging of coronary perfusion defects. However, the behaviour of this tracer in viable and necrotic tissues within the ischaemic area at risk is still being debated. In a clinically relevant canine model, dogs were submitted either to a 24-h permanent occlusion (group 1) of the left descending coronary artery (LAD) or to a 90-min LAD occlusion followed by 22.5 h reperfusion (group 2). 99mTc-MIBI and radiolabelled microspheres were injected 3 h before sacrifice. After delimiting the area at risk and the infarct by Evans blue perfusion and triphenyltetrazolium chloride staining, heart slices were imaged by scintigraphy and tissue radioactivity measured in a gamma-counter. In the necrotic area of both groups, the 99mTc-MIBI distribution was proportional to the myocardial blood flow, approximating a 1:1 ratio (identity line slope 1, intercept 0) with highly significant correlation coefficients (group 1 r = 0.87, group 2 r = 0.86), whereas in the viable-ischaemic area of both groups, the data points are widespread above and below the identity line, indicating both over- and underestimations of blood flow in these tissue areas. These results were more pronounced following reperfusion as compared with permanent occlusion. Multiple linear regression analysis confirms differences (P less than 0.001) in 99mTc-MIBI distributions between the viable-ischaemic and the necrotic zones. Delineation of the ischaemic area at risk was possible only with permanent occlusion. A hypoperfused area was observed after reperfusion but differs from the anatomical infarcted area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Single photon emission computed tomography with technetium-99m hexakis 2-methoxyisobutyl isonitrile in acute myocardial infarction before and after thrombolytic treatment: assessment of salvaged myocardium and prediction of late functional recovery.

Single photon emission computed tomography (SPECT) with technetium-99m hexakis 2-methoxyisobutyl isonitrile was investigated as a method to evaluate the results of intravenous thrombolytic treatment in 14 patients (11 men and 3 women) with acute myocardial infarction admitted to the coronary care unit within 4 h of the onset of symptoms. All patients received an injection of 740 MBq of the tracer before starting the thrombolytic therapy, and isonitrile tomography was performed 3 to 4 h later. The tomographic study was repeated 5 days after the acute event. The results of thrombolytic treatment were independently evaluated taking into account the clinical, electrocardiographic (ECG) and enzymatic data and the findings of left ventricular and coronary angiography. Furthermore, all patients were studied with two-dimensional echocardiography on admission, 5 days later and 1 month later. The site and extent of the perfusion defects on admission scintigraphy were consonant with the ECG and echocardiographic findings. A good correlation could be established between the 5 day scintigraphic estimate of infarct dimension and the enzymatic infarct size (r = 0.907, p less than 0.00002). The comparison between pre- and postthrombolytic treatment images enabled the identification of successful and unsuccessful reperfusion even in patients whose other noninvasive findings were inconclusive. Finally, the reduction in defect size predicted late functional improvement that was demonstrated by echocardiography performed 1 month later (r = 0.89, p less than 0.00005). The results of the study suggest the feasibility and the possible usefulness of isonitrile tomography in demonstrating the presence and size of myocardial damage and in assessing the extent of myocardial salvage after thrombolytic therapy in acute myocardial infarction.

Aged↗

PubMed1990

99mTc-MIBI (RP-30) to define the extent of myocardial ischemia and evaluate ventricular function.

99mTc-MIBI, a new myocardial perfusion agent, is a technetium labeled isonitrile derivative. We have taken advantage of the physical characteristics of 99mTc to combine at rest, post infarction, ventricular function studies with analysis of perfusion. We have studied at rest and at stress, 22 patients with coronary artery disease selected on the basis of an abnormal coronary angiogram or on the basis of a positive exercise ECG stress test for symptomatic angina. We have also studied, at rest only, 20 patients with a previous myocardial infarction. A comparative thallium planar scintigraphy was obtained for all patients. The sensitivity of 99mTc-MIBI scintigraphy for detecting individual vessel lesions at stress was 88% as compared with 83% for 201Tl. Sensitivity was higher in patients with previous myocardial infarction (93% for the 2 isotopes) than in patients without (85% for 99mTc-MIBI versus 81% for 201Tl). Segmental myocardial correspondence between 99mTc-MIBI and 201Tl was very close (92%). The overall sensitivity for the detection of acute myocardial infarction reached respectively 91% for 99mTc MIBI and 87% for 201Tl. The specificity in the regions corresponding to arteries not involved was excellent for both tracers as we did not observe any false positive result. This is important information but it does not correspond to the specificity to detect coronary artery disease in the overall patient population. The correlation between first pass left ventricular ejection fraction obtained with 99mTc-MIBI and equilibrium left ventricular ejection fraction obtained with 99mTc red cells was excellent (r = 0.96). It was not as good but was still satisfactory for the right ventricle (r = 0.75).(ABSTRACT TRUNCATED AT 250 WORDS)

Contrast Media↗

PubMed1994

First evaluation of technetium-99m dimercaptopropionyl albumin as a possible tracer agent for ventriculography in a volunteer.

Technetium-99m labelled red blood cells (99mTc-RBCs) are the standard radiopharmaceutical for radionuclide ventriculography but suffer from some practical disadvantages such as risk of viral contamination and lengthy preparation (in vitro labelling) or poor labelling efficiency due to patient medication interactions (in vivo labelling). 99mTc-labelled human serum albumin (HSA) is not really a valuable alternative as the activity diffuses too rapidly out of the vascular space due to the weak binding of the radionuclide. We have modified HSA by reaction with N-hydroxysuccinimidyl 2,3-di(S-acetylmercapto)propionate (SAMP) to introduce a varying number of 2,3-dimercaptopropionyl (DMP) side chains. The resulting DMP-HSA can be rapidly labelled with 99mTc at room temperature by simple addition of stannous ions and eluate of a 99mTc generator. After evaluation in mice and rabbits, two different 99mTc-DMP-HSA preparations - obtained after reaction of SAMP with albumin in a molar ratio of, respectively, 8:1 and 16:1 - were tested in a volunteer and compared to 99mTc-RBCs. The blood time-activity curves of the three preparations were quite similar but both 99mTc-DMP-HSA preparations were excreted much less into the urine than 99mTc-RBCs. Ventriculography was performed with the three tracer agents, each time with a 1-week interval. In the three studies, the heart was clearly visualized and the left and right ventricle could be easily delineated. The ejection fractions obtained after administration of the three preparations were similar. With both 99mTc-DMP-HSA preparations the low activity in the spleen was a distinct advantage and facilitated delineation of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocytes↗

PubMed1990

Detection and location of myocardial infarction using technetium-99m sestamibi imaging at rest.

Technetium-99m (Tc-99m) sestamibi imaging at rest has been used to detect and localize myocardial infarction. The largest study to date is a cooperative study of 146 patients in 17 institutions. There were 24 normal subjects and 122 patients with documented myocardial infarction based on clinical, enzymatic or electrocardiographic criteria. The presence of segmental myocardial perfusion defects was compared to the presence of a Q wave on the electrocardiogram or wall motion abnormality on gated blood pool scans, performed within 48 hours of the Tc-99m sestamibi study. Of the 122 infarct patients, 118 (97%) showed perfusion abnormalities by Tc-99m sestamibi imaging. A perfusion defect was found in 110 (99%) of 111 patients with a Q wave and a wall motion abnormality, 113 (99%) of 114 patients with a wall motion abnormality and 113 (98%) of 115 patients with a Q wave. Of the 24 normal subjects, 22 (92%) had normal Tc-99m sestamibi images. In 75% of 1,986 segments, both a Tc-99m sestamibi defect and a regional wall motion abnormality on gated blood scans were present. In 11% of segments, wall motion was normal but Tc-99m sestamibi imaging was abnormal; in 14% of segments, wall motion was abnormal and Tc-99m sestamibi images were normal. In the 24 control subjects, 99% of the segments were normal. Thirty-eight patients had coronary angiography. A close relation existed between the coronary anatomy and myocardial Tc-99m sestamibi uptake. All 9 territories supplied by an occluded vessel and poor collaterals had grade 0 uptake (scale 0 to 2: 0 = markedly reduced; 2 = normal).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Technical aspects of myocardial SPECT imaging with technetium-99m sestamibi.

Most reports to date using single photon emission computed tomography (SPECT) with technetium-99m (Tc-99m) sestamibi have used acquisition parameters that were optimized for thallium-201. To fully utilize the superior imaging characteristics of Tc-99m sestamibi, there is a need to optimize the technical aspects of SPECT imaging for this agent. Performance can be enhanced through the careful selection of optimal radiopharmaceutical doses, imaging sequences, acquisition parameters, reconstruction filters, perfusion quantification methods and multidimensional methods for visualizing perfusion distribution. The current report describes theoretical considerations, phantom studies and preliminary patient results that have led to optimized protocols, developed at Emory University and Cedars-Sinai Medical Center, for same-day rest-stress studies, given existing instrumentation and recommended dose limits. The optimizations were designed to fit a low-dose-high-dose rest-stress same-day imaging protocol. A principal change in the acquisition parameters compared with previous Tc-99m sestamibi protocols is the use of a high-resolution collimator. The approach is being developed in both prone and supine positions. A new method for extracting a 3-dimensional myocardial count distribution has been developed that uses spherical coordinates to sample the apical region and cylindrical coordinates to sample the rest of the myocardium. New methods for visualizing the myocardial distribution in multiple dimensions are also described, with improved 2-dimensional, as well as 3- and 4-dimensional (3 dimensions plus time) displays. In the improved 2-dimensional display, distance-weighted and volume-weighted polar maps are used that appear to significantly improve the representation of defect location and defect extent, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Graphics↗

PubMed1991

Comparison of tomographic and planar imaging for the evaluation of thrombolytic therapy in acute myocardial infarction using pre- and post-treatment myocardial scintigraphy with technetium-99m sestamibi.

Pre- and post-treatment myocardial scintigraphy with technetium-99m hexakis 2-methoxy-isobutyl-isonitrile (Tc-99m sestamibi) was performed in patients who underwent thrombolytic therapy for acute myocardial infarction comparing planar imaging and single-photon emission computed tomography (SPECT). Twenty-one patients were injected with Tc-99m sestamibi before thrombolytic treatment. SPECT and planar imaging were acquired after completion of the treatment. The scintigraphy was repeated 5 days later in 20 subjects. Planar and SPECT studies were evaluated using an uptake score. Patients were divided according to the status of the infarct-related vessel (patent in 13 patients, group 1, and occluded in seven, group 2) and to the presence of functional recovery in serial echocardiographic controls (present in 10 patients, group A, and absent in 10, group B). The scintigraphic defect extent in the 5-day images correlated with the enzymatic infarct size: SPECT: r = 0.75, p less than 0.0002; planar: r = 0.68, p less than 0.002. The decrease of the uptake defects correlated with the reduction of the left ventricular wall asynergy (admission versus 1 month echocardiogram): SPECT: r = 0.92, p less than 0.000001; planar: r = 0.82, p less than 0.00001. The percent decrease of the uptake defects was significantly higher in patients in group 1 and group A compared with group 2 and, respectively, group B--SPECT: group 1: 51.4 +/- 27.7 versus group 2: 13.1 +/- 8.6, p less than 0.02; group A: 64.2 +/- 15.3 versus group B: 11.9 +/- 8.1, p less than 0.0002; planar group 1: 41 +/- 30.4 versus group 2: 7.7 +/- 6.2, p less than 0.05; group A: 52.5 +/- 24.3 versus group B: 6.1 +/- 6, p less than 0.0002. This study confirms the reliability of pre- and post-treatment myocardial scintigraphy with Tc-99m sestamibi for evaluating the outcome of thrombolytic treatment in myocardial infarction. The results seems slightly more accurate using SPECT, but a simple three-view planar study also gives useful data.

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