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Serial changes in myocardial perfusion using tomographic technetium-99m-hexakis-2-methoxy-2-methylpropyl-isonitrile imaging following reperfusion therapy of myocardial infarction.

Resting tomographic myocardial perfusion images using technetium-99m-hexakis-2-methoxy-2-methylpropyl-isonitrile (Tc-Sestamibi) were obtained in 25 patients during their first myocardial infarction. Tc-Sestamibi was injected intravenously before acute reperfusion therapy, and repeated twice, at 18-48 hr, and at 6 to 14 days. Reperfusion was successful in 19 patients. In the patients with successful reperfusion, there was a mean decrease in the amount of hypoperfused myocardium between the initial and second studies (-9% +/- 12%, p = 0.004) and a further decrease between the second and final studies (-10% +/- 12%, p = 0.002). Nine of these 19 patients (47%) had evidence of significant improvement at the time of the second study. In six patients, significant improvement was not evident until the final study. Although tomographic imaging with Tc-Sestamibi following reperfusion therapy may show improvement in perfusion at 18-48 hr, the full extent of improvement is usually not evident until later.

Adult↗

Pharmacokinetics of technetium-99m-MAG3 in humans.

Technetium-99m-mercaptoacetylglycylglycylglycine (99mTc-MAG3) is introduced to replace o-iodohippurate (OIH) for renal function studies. For interpretation of clinical findings, extensive pharmacokinetic studies were performed on patients. These showed that 99mTc-MAG3, compared with OIH, has a higher plasma-protein binding, an essentially higher intravascular concentration, a smaller volume of distribution and, with practically identical biologic half-lives, a correspondingly lower clearance. Simultaneous steady-state measurements resulted in a 1.5-fold higher clearance of OIH than of 99mTc-MAG3 (n = 124). Competitive inhibition of the tubular transport system by p-aminohippurate (PAH) (20 patients) revealed a distinctly higher suppression of the 99mTc-MAG3 clearance than of OIH which indicates a lower affinity of the 99mTc complex to the tubular cell. The plasma extraction efficiencies of both agents, measured during surgery (n = 5), did not indicate an extrarenal elimination of 99mTc-MAG3. This new radiopharmaceutical is a pragmatic alternative to OIH and offers advantages not only for scintigraphic imaging but is also suited for quantitative renal function studies.

Humans↗

Quantitative analysis of planar technetium-99m-sestamibi myocardial perfusion images using modified background subtraction.

Standard interpolative background subtraction, as used for thallium-201 (201Tl), may create artifacts when applied to planar technetium-99m-Sestamibi (99mTc-Sestamibi) images, apparently because of the oversubtraction of relatively high extra-cardiac activity. A modified background subtraction algorithm was developed and compared to standard background subtraction in 16 patients who had both exercise-delayed 201Tl and exercise-rest 99mTc-Sestamibi imaging. Furthermore, a new normal data base was generated. Normal 99mTc-Sestamibi distribution was slightly different compared to 201Tl. Using standard background subtraction, mean defect reversibility was significantly underestimated by 99mTc-Sestamibi compared to 201Tl (2.8 +/- 4.9 versus -1.8 +/- 8.4, p less than 0.05). Using the modified background subtraction, mean defect reversibility on 201Tl and 99mTc-Sestamibi images was comparable (2.8 +/- 4.9 versus 1.7 +/- 5.2, p = NS). We conclude, that for quantification of 99mTc-Sestamibi images a new normal data base, as well as a modification of the interpolative background subtraction method should be employed to obtain quantitative results comparable to those with 201Tl.

Algorithms↗

A comparative study of renal scintigraphy and clearance with technetium-99m-MAG3 and iodine-123-hippurate in patients with renal disorders.

The aim of this study was to compare kit prepared technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) with our routine radiopharmaceutical, iodine-123-hippurate our routine radiopharmaceutical, iodine-123-hippurate ([123I]OIH) for renal dynamic scintigraphy. Seventeen patients with different nephrologic disorders or hypertension were first studied with OIH and then reinvestigated with MAG3 2-8 days later. Renal MAG3 gamma camera images were almost identical with those of OIH except for higher (p less than 0.01) liver-to-background ratios at 20 min postinjection, irrespective of kidney function. Urinary peristalsis was visible longer and more clearly in the MAG3 studies. MAG3 and OIH renograms showed identical relative kidney uptake (r = 0.99), but elimination of MAG3 from the kidneys was slower (p less than 0.01). The plasma clearance of MAG3 was lower than that of OIH, but correlated (r = 0.92) significantly. The plasma distribution volume and content in blood cells was lower (p less than 0.01), but the binding of MAG3 to plasma proteins was higher, 90%, as compared with 74% for OIH, p less than 0.01. Urinary excretion expressed as a percent of the given dose 60 min after injection was the same for the two substances. Thus, there are some significant differences in the renal handling, plasma distribution, and cell penetration between MAG3 and [123I]OIH. MAG3, however, seems to have particular qualifications as a radionuclide for dynamic renal scintigraphy, especially in patients who require acute investigations or in those with low renal function.

Gamma Cameras↗

Spontaneous return of renal flow and function on technetium-99m scan in a patient with renal artery thrombosis following angioplasty.

Failure to visualize a kidney on radionuclide scanning using technetium-99m (99mTc) chelates and other renal radiopharmaceuticals such as iodine-131 hippuran has been described as potentially misleading in patients who have acute renal failure due to acute tubular necrosis and urinary tract obstruction. Such failure has not been described in a single kidney nor following angioplasty. The authors report a patient in whom a kidney was not visualized on 99mTc diethylenetriamine penta-acetic acid dynamic and serial scanning 3 days after renal angioplasty. The kidney was believed to be infarcted. Three months later there was almost complete recovery of renal function.

Adult↗

Indium-111-labeled leukocyte and technetium-99m-sulfur colloid uptake by a malignant fibrous histiocytoma: phagocytosis by tumor cells?

Indium-111-labeled leukocyte imaging, performed on a patient with a calcified mass in the right thigh, demonstrated labeled leukocyte accumulation in this mass. Technetium-99m-sulfur colloid imaging was performed to differentiate labeled leukocyte uptake in heterotopic bone marrow from uptake in a focus of infection. Leukocyte and sulfur colloid images were virtually identical, and the study was interpreted as without evidence of infection. Excision of the mass revealed an angiomatoid malignant fibrous histiocytoma with metaplastic bone formation. While no marrow elements were present in either the tumor or the metaplastic bone, phagocytosis of leukocytes by tumor cells was identified. Phagocytosis of leukocytes by tumor cells may be another cause of white cell accumulation in uninfected neoplasms.

Adult↗

Radiolabeling of erythrocytes with technetium-99m: role of band-3 protein in the transport of pertechnetate across the cell membrane.

This study analyzes the transport characteristics of the pertechnetate anion across membranes of human erythrocytes during labeling with technetium-99m (99mTc). Transport of this anion is inhibited after incubation at low temperature, indicating the involvement of a process with high activation energy. Transport is also decreased by two well-known inhibitors of the band-3 anion transport system and is not affected by inhibition of the Na/K/Cl co-transport system. From these results we conclude that, in the process of labeling red blood cells with 99mTc, the pertechnetate anion may reach the interior of the erythrocyte through the band-3 anion transport system.

Anion Exchange Protein 1, Erythrocyte↗

Effect of pertechnetate source and age on the radiochemical purity of technetium Tc 99m exametazime.

The radiochemical purity of technetium Tc 99m exametazime preparations was evaluated by comparing pertechnetate sources and sodium pertechnetate Tc 99m ages. Vials of exametazime were prepared using sodium pertechnetate Tc 99m that was obtained from two brands of generators and up to five hours after elution. Radiochemical purity was determined by using instant thin-layer chromatography. Substantial variability in radiochemical purity existed within and between lots of exametazime. There was little difference in radiochemical purity between the two brands of generator and among the various ages of eluant. The radiochemical purity was not significantly affected by the source or age of sodium pertechnetate Tc 99m used in this study.

Chromatography, Thin Layer↗

Urine excretion of inhaled technetium-99m-DTPA: an alternative method to assess lung epithelial transport.

Technetium-99m DTPA clearance (99mTc-DTPA) clearance measured by a gamma camera or a scintillation probe not only reflects epithelial transport, but is also influenced by an unknown amount of mucociliary clearance depending on particle size and aerosol deposition. This is confirmed by factor analysis of dynamic inhalation studies. Assessment of epithelial absorption by urinary excretion of inhaled 99mTc-DTPA is largely independent of aerosol lung deposition. Twenty-four-hour excretion reflects the amount of aerosol cleared by absorption, while two-hour excretion is a quantitative measure of the aerosol absorption rate from the epithelium into blood. Urinary 99mTc-DTPA excretion of two aerosols with different particle size correlated significantly (p less than 0.001) with analysis of lung clearance curves. A very similar regression in the form of a cumulative exponential function was found with both aerosols. Two-hour urine values of nonsmokers differed significantly from those of smokers or patients with active interstitial or infectious lung disease. This alternative procedure is suited as a bedside test and holds promise for patient monitoring and follow-up.

Administration, Inhalation↗

Effect of mitochondrial and plasma membrane potentials on accumulation of hexakis (2-methoxyisobutylisonitrile) technetium(I) in cultured mouse fibroblasts.

Hexakis(2-methoxyisobutylisonitrile) technetium(I) (Tc-MIBI) is representative of a class of 99mTc-based lipophilic cationic myocardial perfusion imaging agents. To test the hypothesis that the mechanism of cellular uptake may involve distribution across biologic membranes in response to membrane potential, Tc-MIBI net uptake and retention were determined in cultured mouse BALB/c 3T3, NIH 3T3, and v-src transformed NIH 3T3 fibroblasts as well as in cultured chick embryo heart cells. Isovolumic depolarization of plasma membrane potentials with 130 mM K 20 mM Cl buffer decreased Tc-MIBI net cell uptake in all preparations. In BALB/c 3T3 cells, depolarizing mitochondrial membrane potential with valinomycin in high K buffer or with the protonophore CCCP inhibited net uptake and retention of Tc-MIBI while hyperpolarizing mitochondrial and plasma membrane potentials with the K+/H+ exchanger nigericin increased Tc-MIBI net uptake. These results indicated that net cellular uptake and retention of Tc-MIBI in fibroblasts were determined by both mitochondrial and plasma membrane potentials; the gamma-emitting properties of Tc-MIBI may therefore raise the possibility of monitoring membrane potential in vivo.

Animals↗

Preoperative and postoperative technetium-99m pyrophosphate myocardial scintigraphy in the assessment of operative infarction in coronary artery surgery.

The incidence of operative myocardial infarction was assessed by electrocardiogram (ECG) and technetium-99m pyrophosphate (99mTc-PyP) myocardial scintigrams in 89 consecutive patients undergoing coronary artery bypass grafting (CABG). Myocardial scintigrams were performed on the day before operation and repeated 2 to 3 days postoperatively. All patients survived operation, with three in-hospital deaths not related to myocardial infarction (mortality rate 3 percent). Operative infarction was assessed to have occurred in four of 89 patients (4 percent). Two had new Q waves and positive scintigrams; one, major ST-T wave changes and a positive scintigram; and the fourth, new Q waves without a positive scintigram. Three further patients (3 percent) had Q waves and positive scintigrams postoperatively, but myocardial infarction was evolving before anesthesia and operation. Twenty-seven of 89 patients (30 percent) were found to have abnormal scintigrams preoperatively. In two patients, both operated upon with evolving myocardial infarction, the scintigram was worse postoperatively. In 13 patients the scintigram was improved after operation. In 12 patients (13 percent) the abnormal preoperative scintigram was unchanged after operation. Preoperative and postoperative myocardial scintigrams and ECG's must be compared to assess the incidence of operative myocardial infarction in patients undergoing CABG.

Adult↗

Increased lung uptake on technetium-99m-sulfur colloid liver-spleen scans in patients with hepatic venoocclusive disease following bone marrow transplantation.

Three patients who developed signs and symptoms of liver dysfunction following autologous bone marrow transplantation showed varying degrees of increased lung uptake on technetium-99m-sulfur colloid (99mTc-SC) liver-spleen-scans and were subsequently demonstrated to have hepatic venoocclusive disease (VOD) at autopsy. Although increased lung uptake of labeled colloid has been noted in solid organ and bone marrow transplant patients, an association between this phenomenon and VOD has not been previously reported.

Adult↗

Hepatic uptake of technetium-99m HM-PAO in a fetus.

The normal biodistribution of technetium-99m HM-PAO ([99mTc]HM-PAO) includes significant uptake in the brain, liver, and kidneys. A pregnant patient studied with [99mTc] HM-PAO to confirm brain death provided an opportunity to examine the transplacental distribution of this radio-pharmaceutical in the unborn fetus. Uptake in the fetus after transplacental delivery is almost exclusively hepatic with a small amount of biliary excretion.

Adult↗

Myocardial uptake of technetium-99m stannous pyrophosphate in experimental viral myopericarditis.

Distribution of technetium-99m stannous pyrophosphate was studied in mice with experimentally induced viral myopericarditis. Myocardial and bone uptakes of Tc-PPi were compared in 55 mice inoculated with coxsackievirus B3 (Nancy strain). The myocardium-to-bone uptake ratio in 33 mice with myopericarditis was increased to a greater extent than that seen in 22 mice without myopericarditis (p less than 0.001). In the severely involved heart, the uptake per gram exceeded that in the bone. Myocardial uptake in myopericarditis can be visualized on a whole-body image using a pinhole collimator and a left lateral view. Our experimental studies suggest the potential clinical usefulness of myocardial scintigraphy in viral myopericarditis.

Animals↗

Uptake of the cation hexakis(2-methoxyisobutylisonitrile)-technetium-99m by human carcinoma cell lines in vitro.

Uptake of the cationic compound hexakis(2-methoxyisobutylisonitrile)-technetium-99m ([99mTc]MIBI) was examined in nine human tumor cell lines. The concentration of [99mTc]MIBI after a 1-h incubation with the compound varies from 5 to 28% of the activity in the external medium. In contrast, normal V79 cells (Chinese hamster lung fibroblasts) and human peripheral blood mononuclear cells exhibit a minimal uptake of less than 2% of the activity in the medium. Kinetic experiments with SW-13 cells indicate a rapid uptake over time (t1/2 of 10 min) until a steady state is approached whose concentration appears directly correlated with the extracellular concentration of [99mTc]MIBI with no evidence of saturation over the range tested (10(-12)-10(-9) M). [99mTc]MIBI is taken up by a temperature dependent process that is restricted to living cells. Microautoradiography demonstrates that [99mTc]MIBI is clustered in the cytoplasm around the nucleus. Given that depolarizing the plasma membrane potential in high K+ buffer results in lowering the uptake of [99mTc]-MIBI and that alteration of the mitochondrial membrane potential with valinomycin or nigericin induces, respectively, a significant decrease or increase of [99mTc]MIBI uptake, we propose that the plasma and mitochondrial membrane potentials play a major role in the uptake. These data suggest that the gamma emitter [99mTc]MIBI exhibits interesting tumor cell interaction characteristics with promise for in vivo tumor imaging.

Autoradiography↗

Effect of metabolic inhibition on technetium-99m-MIBI kinetics in cultured chick myocardial cells.

Cellular uptake characteristics of hexakis(methoxyisobutylisonitrile)technetium(I) ([99mTc]MIBI), a myocardial perfusion imaging agent, were evaluated in cultured chick embryo heart cells. Myocyte net uptake of 99mTc-MIBI approached a plateau with a half-time of 9.3 +/- 1.5 min (mean +/- s.e.m.; n = 10). Tracer [99mTc]MIBI showed apparent competitive displacement by carrier [99Tc]MIBI at relatively high molar ratios ([99mTc]MIBI/[99Tc]MIBI) indicating a low affinity cellular retention process (apparent KD approximately 7 x 10(-5)). Metabolic inhibition induced by pre-incubation of cells for 2.5 hr in rotenone (10 microM), iodoacetate (1 mM), or both metabolic inhibitors together reduced 1-min [99mTc] MIBI uptake to 74.1% +/- 8.0% (p less than 0.05), 6.2% +/- 3.4% (p less than 0.01), and 10.1% +/- 3.6% of control (p less than 0.01), respectively (n = 11-12). Half-maximal inhibitory concentration of iodoacetate was approximately 5 microM. Iodoacetate inhibition of [99mTc]MIBI uptake kinetics was time-dependent; no significant effect on [99mTc]MIBI uptake was seen during the first 60 min of metabolic inhibition despite significant depletion of ATP content determined on the same preparations (control ATP: 40.2 nmoles/mg protein versus iodoacetate incubation: 2.8 nmoles/mg protein; p less than 0.01). However, prolonged metabolic blockade did eventually depress 1-min [99mTc]MIBI uptake. These data indicate that a late component of myocardial cell injury can depress [99mTc]MIBI cellular uptake.

Animals↗

[The use of bone scintigraphy with technetium 99 m pyrophosphates in the diagnosis of algodystrophies. A report on 74 observations (author's transl)].

Bone scintigraphy with technetium 99m pyrophosphates was used to study a series of 74 cases of algodystrophies. Though non-specific, this investigation was the determining factor for confirming the diagnosis in more than 48% of cases, by demonstrating early bone hyperfixation, its topographical characteristics, and the return to normal conditions after 3 to 12 months. Bone hyperfixation has to be exaluated together with clinical, biological, and radiological signs when considering the diagnosis, and though in half the cases it is not indispensable for diagnosis, it is always of value for determining the amount of extension of the algodystrophic process.

Adult↗