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PubMed1999

Myocardial uptake of technetium-99m-furifosmin (Q12) versus technetium-99m-sestamibi (MIBI).

AIM: This study was performed to compare the myocardial uptake of Tc-99m-furifosmin (Q12) versus Tc-99m-sestamibi (MIBI) in correlation to the whole-body uptake under resting conditions. METHODS: 21 patients with coronary artery disease and no rest ischemia were examined. A whole-body scan was performed 60 min. p.i. under resting conditions. A quantification of the uptake (whole-body, heart and right lung) was done by ROI technique. RESULTS: The heart-to-lung ratio of Q12 (1.56 +/- 0.191) was significantly lower as compared to MIBI (1.94 +/- 0.197; p < 0.01). In contrast, the heart-to-whole-body ratios (Q12 versus MIBI: 0.027 +/- 0.012 versus 0.026 +/- 0.004; p < 0.76) did not differ. The lung-to-whole-body ratio (Q12 versus MIBI: 0.018 +/- 0.009 versus 0.013 +/- 0.002; p < 0.17) were different, but did not reach significance. CONCLUSION: These data show that under resting conditions the total myocardial uptake of Q12 does not differ significantly from that of MIBI. However, the pulmonary uptake of Q12 is slightly higher, resulting in a significant lower heart-to-lung ratio. These findings imply a lower image quality of Q12 compared to MIBI.

Adult↗
PubMed1975

[Technetium polyphosphate and technetium diphosphonate. A comparative study].

99mTc-labelled phosphates are the bone seeking agents of choice. The comparison of 99mTc-polyphosphate (Poly-P) and 99mTc-ethane-1-hydroxy-1,1-diphosphonate (EHDP) shows a better in vitro stability of the latter during the first two hours after preparation. The blood clearance of EHDP is superior to Poly-P resulting in reduced background activity at scanning time. Renal excretion over a 4-hour period of urine sampling showed no significant differences between both substances. Blood activity is independent of diuresis.

Adult↗
PubMed1992

Measurement of myocardial blood flow using a co-injection technique for technetium-99m-teboroxime, technetium-96-sestamibi and thallium-201.

We have compared apparent myocardial blood flow (MBFapparent) indicated by 99mTc-teboroxime, 96Tc-sestamibi and 201TI to true MBF indicated by radiolabeled microscopheres using a technique for the co-injection of four radionuclides in the same animal. Studies were performed using rats in a single-pass model to obtain global MBF and using dogs in a multiple-pass model to determine regional MBF. To provide a wide range of MBF, adenosine was administered intravenously and the left anterior descending coronary artery was then ligated in the dogs, or hypercapnia was induced by decreasing respiratory frequency in the rats. The microsphere formula for determining MBF was applied to all agents. When MBFapparent was plotted as a function of true MBF, the ability of each agent to measure changes in true MBF was demonstrated by the proximity of the plotted function to the line of identity. For both the single and multiple-pass studies, statistical analysis of the nonlinear relationship between MBFapparent and true MBF showed that 201TI and 99mTc-teboroxime approximate true MBF better than 96Tc-sestamibi (p less than 0.001) under the conditions used in the present studies. In the single-pass studies, 99mTc-teboroxime approximated true MBF better than 201Tl (p less than 0.05), but in the multiple-pass experiments, 201Tl approximated true MBF better than 99mTc-teboroxime in only one dog (p less than 0.01) with no difference in the other two. Determination of the permeability-surface area product, PS, for each agent shows that the higher fidelity to true MBF obtained with 201Tl and 99mTc-teboroxime is related to substantially greater PS values for these agents relative to 96Tc-sestamibi.

Animals↗
PubMed1992

Intrasubject comparison between technetium-99m-ECD and technetium-99m-HMPAO in healthy human subjects.

The pharmacokinetics and quality of planar and SPECT brain imaging of two 99mTc-labeled brain perfusion agents, d,l-hexamethyl propylene amine oxime (HMPAO) and ethyl cysteinate dimer (ECD), were compared in seven healthy, normal subjects. Both radiopharmaceuticals showed rapid brain uptake and had a net brain washout of less than 5% during the first 20 min after drug administration. However, during the same time period, 99mTc-ECD images of the head showed significantly less background facial uptake and retention when compared to 99mTc-HMPAO images. The brain-to-background contrast ratio of 99mTc-ECD (brain/neck) continued to improve over time and by 5 hr postadministration was 17 to 1 versus 2 to 1 for 99mTc-HMPAO. SPECT brain images of both agents show gray/white matter ratios that were unchanged over time and an intracerebral distribution consistent with blood flow. A blind read of these SPECT images also shows 99mTc-ECD to produce images that were "easier to interpret" with less extracerebral activity as compared to 99mTc-HMPAO. Repeat, whole-body planar spot imaging suggests that 99mTc-ECD was cleared more rapidly from the body than was 99mTc-HMPAO.

Adult↗
PubMed1992

Technetium- and rhenium-labeled progestins: synthesis, receptor binding and in vivo distribution of an 11 beta-substituted progestin labeled with technetium-99 and rhenium-186.

In an effort to develop radiopharmaceuticals useful for the diagnostic imaging of steroid receptor-positive breast tumors, we have radiolabeled an analog of the antiprogestin RU486 (mifepristone), modified to incorporate an N2S2 chelate system in the 11 beta-position, with 99Tc, 99mTc, and 186Re. For the 99Tc-labeled analogs (3), a syn pair and two individual antidiastereomers (linker methylene versus metal-oxo, relative to the N2S2 plane) were isolated. In competitive radiometric binding assays, the syn pair (3syn1,2) had affinity for the progesterone receptor that was 25% that of (promegestone) R5020 (or 161% that of progesterone), and the individual anti-diastereomers had affinities of 47% (3anti1) and 7% (3anti2) that of R5020 (or 303% and 45% that of progesterone). The specific-to-nonspecific binding ratio of the 99mTc (4) and 186Re (5) 11 beta-linked syn systems are 75/25 and 54/46, respectively. In vivo, conjugates 4 and 5 showed progesterone receptor-mediated uptake in rat uterus, but also high uptake in non-target tissues, presumably because of the high lipophilicity of the metal complexes. Modified systems may be useful in vivo as receptor-directed agents for diagnostic imaging or treatment of steroid receptor-positive tumors.

Animals↗
PubMed1995

Technetium-99m-tetrofosmin in dipyridamole-stress myocardial SPECT imaging: intraindividual comparison with technetium-99m-sestamibi.

UNLABELLED: Tetrofosmin is a new 99mTc-labeled myocardial perfusion imaging agent. Biodistribution studies suggest more favorable heart-to-adjacent organ biokinetics than for 99mTc-sestamibi after injection during exercise. The aim of this work was to determine intraindividually whether tetrofosmin is more suitable than sestamibi for pharmacological stress testing in a 1-day protocol. METHODS: Thirty subjects underwent two similar 1-day, rest and dipyridamole stress imaging protocols: one using tetrofosmin, the other using sestamibi. SPECT was performed 60 min after tracer administration. Myocardial images were analyzed both visually and quantitatively. RESULTS: Heart-to-liver activity ratios measured on the anterior SPECT projections were significantly higher for tetrofosmin than for sestamibi in the rest and stress studies. Heart-to-lung ratios were similar for both tracers. Significant linear correlations between tetrofosmin and sestamibi perfusion indices were found in normals and in patients with proven or suspected coronary artery disease. In segments showing abnormal uptake during stress, the perfusion indices were similar for tetrofosmin and sestamibi at rest and during stress. The degree of reversibility in these segments was also similar for both tracers. Finally, the extent, intensity and severity of perfusion defects were similar for both tracer studies. CONCLUSION: Tetrofosmin has a more optimal biodistribution than sestamibi when used in a 1-day, rest and dipyridamole stress myocardial SPECT imaging protocol. No significant difference in either the quality or diagnostic interpretation of the images could be demonstrated.

Aged↗
PubMed1994

Technetium-99m-labeled monoclonal antibodies: influence of technetium-99m binding sites.

UNLABELLED: A number of 99mTc-labeled monoclonal antibodies (Mabs) are being evaluated for diagnostic applications. Preparations are carried out using both direct and indirect (bifunctional chelating agent, BFCA) labeling procedures in which nonspecific 99mTc binding has been postulated. METHODS: By using the ascorbic acid (AA) reduction mediated direct labeling procedure and diaminotetrathiol (N2S4) as a BFCA method, we examined the role of specific binding sites and aliphatic E amino groups of lysine as nonspecific binding sites for 99mTc. RESULTS: Labeling yields for the direct and N2S4 "regular" preparations averaged 73% +/- 2.8% and 91% +/- 2%, for the "specific" preparations, 60% +/- 3.5% and 75% +/- 2% and for the "nonspecific" preparations 13% +/- 1.0% and 16% +/- 1% respectively. All preparations were evaluated in tumor-bearing mice. The control and specific preparations permitted excellent scintigraphic visualization of tumors; the percentages of specific preparations in the tumors being 2.1% +/- 0.5% and 3.1% +/- 0.4%, respectively. With nonspecific preparations, tumors were not visualized and the percentages of administered radioactivity per gram of tumor were only 0.9% +/- 0.2% and 0.9% +/- 0.3%, respectively. CONCLUSIONS: In these 99mTc labeling procedures, the amino group-mediated nonspecific binding of 99mTc to Mabs can be as high as 16% and contributes to increased liver uptake and decreased tumor uptake of radioactivity.

Animals↗
PubMed1993

In vitro uptake of technetium-99m-teboroxime in carcinoma cell lines and normal cells: comparison with technetium-99m-sestamibi and thallium-201.

Since 201Tl, 99mTc-sestamibi and 99mTc-teboroxime concentrate in cardiac cells through different mechanisms, we compared their uptake in cultured normal cells and carcinoma cell lines in order to define their possible use for tumor evaluation in vivo. Four lines of normal cells from animals, including myocytes from newborn rats, and four lines of human carcinoma cell lines were incubated for 1 hr with 37 kBq of either tracer. Results, expressed in percent of the total activity taken up by 1 million cells, showed a 9% difference between the uptake of teboroxime by normal and carcinoma lines (24.6% +/- 2.8% versus 22.5% +/- 2.1%, respectively, p < 0.05). Mean uptake was 80% higher in tumor than in normal cells for 201Tl (5.39% +/- 1.33% versus 3.00% +/- 1.08%, respectively, p < 0.001) and nearly 4 times higher for sestamibi (5.37% +/- 2.34% versus 1.44% +/- 1.88%, p < 0.001). For both agents, uptake by the myocytes and carcinoma cells was comparable (5.14% +/- 0.11% for 201Tl and 5.28% +/- 1.03% for sestamibi). When the myocytes are excluded from the group of normal cells, the uptake is 112% higher in tumor than in normal cells for 201Tl (5.39% +/- 1.33% versus 2.54% +/- 0.44%, p < 0.001) but it becomes nearly nine times higher for sestamibi (5.37% +/- 2.34% versus 0.60% +/- 0.23%, p < 0.001). It is concluded that these experiments show that the uptake of sestamibi was the most discriminant to separate between normal and malignant cells, while teboroxime was the less discriminant. Potential clinical applications for tumor visualization based on differences in sestamibi and teboroxime uptake could be envisioned.

Animals↗
PubMed1993

Effect of hypoxia on the accumulation of technetium-99m-glucarate and technetium-99m-gluconate by Chinese hamster ovary cells in vitro.

The accumulation of 99mTc-glucarate, an agent recently reported to localize in acutely infarcted myocardium, zones of acute cerebral injury and tumors, has been compared with 99mTc-gluconate in an in vitro system of cultured Chinese hamster ovary fibroblasts. The effects on accumulation of hypoxia and competition with fructose have been studied. Both labeled glucose analogs showed a two- to threefold enhanced accumulation in hypoxic cells relative to aerobic cells. No such enhanced accumulation under hypoxia was observed for the nonsugar tracers pertechnetate and 99mTc-DTPA. The presence of 20 mM fructose reduced the accumulation of 99mTc-glucarate by 30% (p = 0.067) and 99mTc-gluconate by 40% (p < 0.05) in hypoxic cells, but had no significant effect in aerobic cells. These results suggest that both compounds at least partially share a common mechanism of uptake and/or accumulation with fructose.

Animals↗
PubMed1993

Uptake of technetium-99m-teboroxime in cultured myocardial cells: comparison with thallium-201 and technetium-99m-sestamibi.

The effects of metabolic inhibition on the uptake of 99mTc-teboroxime were assessed in cultured myocardial cells and compared with 201Tl and 99mTc-sestamibi. Metabolic impairment was induced by cyanide (CN), a blocker of the mitochondrial respiratory chain, iodoacetate (IAA), an inhibitor of the glycolytic pathway, and ouabain, an inhibitor of Na(+)-K+ sarcolemmal ATPase. Cellular viability was appreciated by the trypan blue exclusion method. The effects of low temperature and of cellular death resulting from osmotic lysis were also assessed. Net cellular uptake of the radiotracers and the amount of proteins in the culture dishes were measured. All experiments were performed in parallel with control conditions and the results were expressed relatively to the control values. Teboroxime uptake was clearly decreased at low temperature (29.6% +/- 2.2% at 0 degree C, p < 0.001), while metabolic inhibition or osmotic lysis had no definite effect. The uptake of 201Tl and sestamibi was severely diminished in the presence of a mixture of 5 mM CN and 0.1 mM IAA, but 201Tl was less resistant than sestamibi (13.7% +/- 0.3% and 73.5% +/- 3.3%, respectively, after 1 hr of preincubation, p < 0.001 for both). Uptake of both tracers was very low in the presence of dead cells (12.1% +/- 1.3% for 201Tl and 4.1% +/- 0.2% for sestamibi, p < 0.001 for both). Ouabain had a detrimental effect only on 201Tl uptake at doses higher than 100 microM. Of these three currently available coronary blood flow imaging agents, teboroxime shows the lowest sensitivity to metabolic impairment.

Animals↗
PubMed1997

SPECT image analysis using statistical parametric mapping: comparison of technetium-99m-HMPAO and technetium-99m-ECD.

UNLABELLED: The goal of this study was to examine the apparent differences in regional cerebral blood flow (rCBF) between two groups of normal individuals who received either of the two tracers, 99mTc-D,L-hexamethylpropylene amine oxide (99mTc-HMPAO, or exametazime) or 99mTc-ethylene-dicysteine diethylester (99mTc-ECD, or bicisate). METHODS: Individuals were screened for drug use, head injury, medication status and other psychiatric and medical illnesses. The two groups were matched for age, sex and race. SPECT measurement of brain perfusion was performed in 35 individuals who received 99mTc-HMPAO and in 55 who received 99mTc-ECD. Subsequent analysis of these scans was done using computer software including Statistical Parametric Mapping and Analyze. Images were intensity-thresholded and spatially normalized to a standardized stereotactic (Talairach) space. This allowed for the objective, quantitative analysis of these data, demonstrating the extent and magnitude of rCBF changes. RESULTS: Our results showed significant changes between these two groups of normal individuals, presumably due to differences in pharmacokinetics between the two radiolabeled tracers. Specifically, large areas of the parietal, occipital and superior temporal cortices were significantly lower in the 99mTc-HMPAO group than in the 99mTc-ECD group. Increases were seen in the subcortical nuclei, parts of the brain stem, hippocampus and small areas of the cerebellum in the 99mTc-HMPAO group as compared to the 99mTc-ECD group. CONCLUSION: We present a method of image analysis to semiquantitatively measure rCBF in SPECT images and the changes seen due to differences between the two radiotracers.

Adult↗
PubMed1998

Technetium-99m-tetrofosmin, technetium-99m-MIBI and thallium-201 uptake in rat myocardial cells.

UNLABELLED: The mechanisms of uptake and intracellular distribution of 99mTc-tetrofosmin, 99mTc-MIBI and 201TI and the behaviors of 99mTc-tetrofosmin and 99mTc-MIBI in relation to Na+ were studied with primary cultures of myocardial cells. METHODS: Both the uptake and the washout of the tracers were sequentially measured. The cells were treated with ouabain, bumetanide, tetrodotoxin, dimethyl amiloride (DMA), nigericin and carbonyl cyanide m-chlorophenylhydrazone (CCCP) to observe the effects of the uptake and intracellular distribution of the traders. Cells equilibrated in buffers with or without Na+ were treated with monensin and DMA to evaluate the effect of Na+ on the accumulation of the tracers. RESULTS: Despite the similarities in uptake kinetics, there was a higher level of retention of 99mTc-tetrofosmin inside the cells. Ouabain, bumetanide and tetrodotoxin did not show any inhibitory effect on the uptake of 99mTc-tetrofosmin and 99mTc-MIBI, whereas they produced various degrees of inhibition of 201TI uptake. DMA produced approximately 35% inhibition of 99mTc-tetrofosmin uptake and 50% inhibition of 99mTc-MIBI uptake. Nigericin increased the uptake of 99mTc-MIBI by the cells. The addition of CCCP produced the release of 38% of the accumulated 99mTc-tetrofosmin and 52%-70% of the accumulated 99mTc-MIBI, indicating that these percentages of accumulation were related to mitochondrial uptake. Neither Na+-free buffer nor monensin had any significant effect on 99mTc-tetrofosmin accumulation, but they both caused increased accumulation of 99mTc-MIBI. CONCLUSION: The uptake of both 99mTc-tetrofosmin and 99mTc-MIBI through the cell membrane is partly related to the Na+/H+ antiporter system. Only part of the accumulated 99mTc-tetrofosmin inside the cells enters into mitochondria; most of the accumulated 99mc-MIBI is related to mitochondrial uptake. This uptake may be related to Na+.

Amiloride↗
PubMed1998

Comparison of technetium-99m-MIBI, technetium-99m-tetrofosmin, ultrasound and MRI for localization of abnormal parathyroid glands.

UNLABELLED: Abnormal parathyroid tissue can be identified by radionuclide imaging with either 99mTc-MIBI or 99mTc-tetrofosmin. This study compared the relative sensitivity of these two agents to localize parathyroid hyperplasia and adenoma. METHODS: Twenty patients with primary (n = 9) or secondary (n = 11) hyperparathyroidism were studied with 99mTc-MIBI and 99mTc-tetrofosmin parathyroid imaging, ultrasonography and MRI. Radionuclide images of the neck were acquired 10 min and 2-3 hr after radiopharmaceutical injection. The images were visually evaluated for abnormal focal areas of increased tracer localization in the neck and mediastinum. A parathyroid gland/normal thyroid tissue activity ratio (referred to as the P/T uptake ratio) was calculated for each positive scan. RESULTS: Of the 46 parathyroid glands surgically explored, the overall sensitivity and specificity of MIBI imaging were 83% and 83% (38/46); tetrofosmin imaging 87% and 83% (40/46); ultrasonography 78% and 40% (36/46); and MRI 80% and 60% (37/46), respectively. Both radiopharmaceuticals performed well in the nine patients found to have adenoma. The sensitivity and specificity of MIBI imaging were 100% and 100% (9/9); tetrofosmin imaging 100% and 100% (9/9); ultrasonography 78% and 67% (7/9); and MRI 100% and 100% (9/9), respectively. In the 37 glands with hyperplasia, MIBI imaging had a sensitivity of 78% and specificity of 75%; tetrofosmin imaging 84% and 75%; ultrasonography 78% and 43%; and MRI 73% and 60%, respectively. CONCLUSION: All imaging techniques localized abnormal parathyroid glands. The radiotracers have equal sensitivity for the localization of abnormal parathyroid glands. The sensitivity of these tracers was high as compared to ultrasonography or MRI.

Adenoma↗