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Technetium-99m APD compared with technetium-99m MDP as a bone scanning agent.

We have investigated the possibilities of technetium-99m-(-3-aminohydroxypropylidene)-1-1-bisphosphon ate ([99mTc]APD) as a bone scanning agent in 14 normal subjects and 28 patients. Similar studies in the same normal subjects and patients were carried out with 99mTc-methylene-bisphosphonate ([99mTc]MDP). The compounds were labeled with 99mTc by means of an electrolytical method; the free pertechnetate content was always under 1%. The [99mTc]APD T1/2 of the third component of the disappearance plasma curve in six normal subjects was 152 +/- 46 min (mean +/- s.d.), while the 24-hr whole-body retention (WBR) was 17.6% +/- 4.6. The [99mTc]MDP value of the 24-hr WBR was 28.6% +/- 3.9 (p less than 0.001). The bone/soft-tissue ratio (B/ST) was investigated in eight control subjects on the eleventh thoracic and the fourth lumbar vertebrae. The B/ST ratios were similar for both APD and MDP studies. In 28 patients with suspected bone metastasis or primary bone disease, bone scintigraphy was carried out; both compounds showed similar findings and the same number of positive results. In five of these patients, the lesion/normal bone ratio was determined with values of 4.6 +/- 2.0 in APD studies and 4.8 +/- 2.3 with MDP. APD was also used in 126 patients; no adverse reactions were observed. The APD dose used i.v. for bone scanning was 200-fold less than those employed by mouth per day, for the treatment of bone disease for long periods. In our experience, APD appears to be an adequate agent for bone scintigraphy.

Adolescent↗

[Follow-up after kidney transplantation. Sequential functional scintigraphy with technetium-99m-DTPA or technetium-99m-MAG3].

Complications following renal transplantation are associated with transplant dysfunction; their frequency and the nonspecificity of clinical symptoms underscore the importance of choosing the correct diagnostic procedure. Sequential function scintigraphy with technetium-99m-MAG3 is noninvasive and facilitates the diagnosis of different types of organ rejection, of drug-induced malfunction and of surgical complications.

Graft Rejection↗

Comparison of modified technetium-99m albumin and technetium-99m red blood cells for equilibrium ventriculography.

UNLABELLED: A newly developed modified form of 99mTc-labeled human serum albumin reconstituted from a kit (99mTc-dimercaptopropionyl-human serum albumin; 99mTc-DMP-HSA) was prospectively compared to 99mTc-labeled red blood cells (RBC) in patients referred for equilibrium radionuclide ventriculography at rest to evaluate its potential use as a blood-pool imaging agent. METHODS: A Paired comparison between 99mTc-DMP-HSA and either in vitro or in vivo 99mTc-labeled RBC was performed within 2 days in 20 patients'. For each study, two sets of images were acquired, starting at 15 min and 180 min postinjection, respectively. Each set consisted of a gated blood-pool cardiac study and a planar static image centered on the patient's thorax. All data were processed by two independent observers. Early and late postinjection parameters were calculated: ejection fraction (EF) value, activity within the main organs surrounding the left ventricle (LV), ratio of activity between the LV and these surrounding organs for each study separately, and temporal (late/early) evolution of the intraorgan activities and of the LV/organ ratios after decay correction. RESULTS: The images and the visual wall-motion analysis were of good quality with both agents in most patients, without significant image degradation at 180 min postinjection. Calculated EF values were highly comparable with the two tracers. Interobserver variability was 0.17% (RBC) and 1.08% (DMP-HSA) for the early EF value (EF1), and 0.62% (RBC) and 0.27% (DMP-HSA) for the late EF (EF2). Mean difference between EF2 and EF1 was 0.74% (Observer 1) and 0.28% (Observer 2) for 99mTc-RBC, and -2.88% (Observer 1) and -2.07% (Observer 2) for 99mTc-DMP-HSA. When comparing 99mTc-DMP-HSA to 99mTc-RBC the mean difference was 1.27% (Observer 1) and 0.36% (Observer 2) for EF1, and -2.35% (Observer 1) and -1.99% (Observer 2) for EF2. Also, the biodistribution and temporal evolution of the organ repartition of both compounds were stable and similar, with values of late/early activity ratios very close to one for all the studied organs [mean intraorgan ratio: 0.946 for 99mTc-RBC (range: 0.881-1.086) and 0.979 for 99mTc-DMP-HSA (range: 0.914-1.141); mean late/early LV/organ ratio: 0.964 for 99mTc-RBC (range: 0.919-1.016) and 0.967 for 99mTc-DMP-HSA (range: 0.912-1.035)]. CONCLUSION: Paired comparison of kit-prepared 99mTc-DMP-HSA to 99mTc-labeled RBC demonstrated that both agents were very closely related regarding as well the calculated EF value as the in vivo stability up to more than 3 hr postinjection. Technetium-99m-DMP-HSA may constitute a practical and useful replacement for 99mTc-labeled RBC.

Erythrocytes↗

Technetium-99m tetrofosmin and technetium-99m sestamibi imaging of multiple metastases from differentiated thyroid carcinoma.

A 79-year-old male with follicular thyroid carcinoma metastasizing to the lung, bone and lymph nodes was subjected to whole-body scintigraphy using technetium-99m tetrofosmin and 99mTc-sestamibi. Both agents delineated the metastatic lesions and the two image qualities were comparable. We believe that 99mTc-tetrofosmin and 99mTc-sestamibi images may be helpful in localizing metastatic foci and substitute for thallium-201 in the follow-up of patients with differentiated thyroid carcinoma.

Adenocarcinoma, Follicular↗

Parathyroid scintigraphy: comparison of technetium-99m methoxyisobutylisonitrile and technetium-99m tetrofosmin studies.

We report the preliminary results of a prospective study demonstrating tetrofosmin uptake in surgically and histologically proven parathyroid adenomas. In ten patients with primary chronic hyperparathyroidism, parathyroid imaging was performed using (1) technetium-99m methoxyisobutylisonitrile (MIBI) and (2) 99mTc-1, 2-bis(bis(2-ethoxyethyl)phosphino)ethane (tetrofosmin) within a time interval of 3-5 days. Both tracers correctly identified the parathyroid adenomas by focal prolonged tracer retention. On visual inspection image contrast was generally higher with MIBI than with tetrofosmin in all the patients studied. Tetrofosmin showed a slower elimination from the parathyroid adenomas than MIBI in six of the ten cases. Our preliminary results show that tetrofosmin, like MIBI, as a feasible, sensitive tracer for parathyroid scintigraphy. For routine use, the rapid kit preparation without heating and the lower radiation dose to the patient make tetrofosmin an alternative tracer for parathyroid scintigraphy. Further evaluation is needed to determine which of the two tracers is the more sensitive for the detection of parathyroid adenomas, and which tracer properties better reflect the degree of endocrine activity.

Adenoma↗

A comparative study of technetium-99m sestamibi and technetium-99m tetrofosmin single-photon tomography in the detection of nasopharyngeal carcinoma.

The intention of this prospective study was to compare the diagnostic potential of technetium-99m sestamibi (MIBI) and a novel radiotracer, 99mTc-Tetrofosmin (Tetro), for the assessment of primary nasopharyngeal carcinoma (NPC) and the differentiation of residual disease from post-therapy changes. A total of 38 patients underwent MIBI and Tetro single-photon emission tomography (SPET) imaging at initial presentation (n=22) or following therapy (n=16). The findings were correlated with computed tomography or magnetic resonance imaging (MRI) on a site-by-site basis. Tumour/background (Tm/Bkg) ratios were obtained on coronal sections. Biopsy (nine patients) and/or 12- to 24-month clinical follow-up data were available in the post-therapy group. All primary disease sites were accurately detected by both imaging studies. Although there was no statistical difference between the two imaging techniques in the detection of primary disease, MIBI was superior to Tetro in the detection of regional lymph node metastases (sensitivity: 95% vs 79%). Tetro and MIBI SPET were true-positive in all patients (n=7) with proven residual/recurrent disease. In nine patients who had no evidence of residual/recurrent tumour, MRI was false-positive in five while Tetro and MIBI SPET were false-positive in two and three patients, respectively. Tm/Bkg ratios were </=1.7 in all false-positive cases except one. Tetro, MIBI and MRI had specificities of 78%, 67% and 44%, and accuracies of 87.5%, 81% and 69%, respectively. The results of Tetro and of MIBI SPET were not statistically different from one another with regard to the prediction of residual/recurrent or metastatic NPC.

Carcinoma↗

Technetium-99m labelled hydrazinonicotinamido human non-specific polyclonal immunoglobulin G for detection of infectious foci: a comparison with two other technetium-labelled immunoglobulin preparations.

Recently a new linker - hydrazinonicotinate (HYNIC) - was introduced for labelling of proteins and peptides with technetium-99m. HYNIC and other linkers have been used for labelling of human non-specific polyclonal immunoglobulin G (hIgG) with 99mTc for the detection of infections. In this study we compared the tissue distribution of three different 99mTc-hIgG preparations in groups of five Wistar rats with a focal intramuscular infection with Staphylococcus aureus. We compared 99mTc-HYNIC-hIgG with 99mTc-hIgG labelled via the so-called Schwarz method (reduction of disulphide bonds) and with the 99mTc-labelled commercially available Technescan-HIG. Unlike the HYNIC linker, in the two other labelling methods free sulph-hydryl groups are involved in the binding of 99mTc. High-performance liquid chromatography analysis of the labelled preparations and of plasma samples revealed aggregate or polymer formation in all three agents; this was least pronounced in the product labelled by means of the Schwarz method. The tested preparations did not show signs of degradation in vitro. The difference in linker chemistry was reflected in the tissue distribution. Thus the biodistribution of 99mTc-HYNIC-hIgG was significantly different from the distribution of the two other preparations: abscess (1.4%+/-0.2%ID/g), muscle, liver, spleen, plasma, lung, bone marrow, and small intestine concentrations were higher at 24 h p.i.; kidney uptake (1.19%+/-0.08%ID/g) was significantly lower. The abscess-to-plasma and the abscess-to-muscle ratios (0.5 and 11, respectively), however, were in the same range for the three preparations tested. Quantitative analysis of the scintigraphs revealed that the total body clearance of 99mTc-HYNIC-hIgG was significantly slower than for the other agents. The abscess uptake of 99mTc-HYNIC-hIgG as a percentage of the remaining body activity was significantly higher. Based on its high abscess uptake, its low uptake in the kidneys and the high percentage of its abscess uptake in relation to the remaining body activity, we conclude that 99mTc-HYNIC-hIgG seems superior to the two other preparations tested for the detection of infections.

Abscess↗

Retention of technetium-99m in infectious foci in rats after release from technetium-99m labelled human non-specific polyclonal immunoglobulin G: a dual-label study with hydrazinonicotinamido and iminothiolano immunoglobulin.

In an effort to contribute to the understanding of the mechanism of uptake of technetium-99m labelled non-specific polyclonal human immunoglobulin G (hIgG) in inflammatory lesions we compared the tissue distribution of double-labelled 99mTc-hydrazinonicotinamido (HYNIC) hIgG-14C and 99mTc-iminothiolano hIgG-14C in groups of five Wistar rats with a Staphylococcus aureus infection of the left calf muscle between 2 h p.i. and 24 h p.i. The stability of the two double-labelled hIgG preparations was evaluated in vitro and in plasma in vivo by high-performance liquid chromatography (HPLC) analysis. At 24 h after injection of 99mTc-HYNIC-hIgG-14C the abscess uptake of 99mTc (1.5% ID/g+/-0.2% ID/g) was significantly higher (P<0.01) than the 14C uptake (1.0% ID/g+/-0.1% ID/g). After injection of 99mTc-iminothiolano hIgG-14C no significant difference (P=0.08) was found between the abscess uptake of the two radionuclides at 24 h p.i. (99mTc: 0.8% ID/g+/-0.1% ID/g; 14C: 0.90% ID/g+/-0.09% ID/g). HPLC analysis of plasma samples revealed release of 99mTc from both double-labelled immunoglobulin preparations. This phenomenon was more pronounced for iminothiolano hIgG than for HYNIC hIgG (43% vs 18%). In most tissues other than abscesses significant differences were also found between the 99mTc and the corresponding 14C uptake. Our results demonstrate that the chemical form in which 99mTc is bound to hIgG severely influences its release from hIgG and its retention in infections.

Abscess↗

Comparison of technetium 99m polyclonal human immunoglobulin and technetium 99m monoclonal antibodies for imaging chronic osteomyelitis. First clinical results.

The accuracy of technetium-99m human immunoglobulin (HIG) for the detection of chronic osteomyelitis (OM) was compared with white blood cell scintigraphy using 99mTc-labelled monoclonal mouse antibodies (MAB). Seventeen patients suspected of having OM in 20 lesions went through three-phase skeletal scintigraphy, HIG scintigraphy and MAB scintigraphy. The final diagnosis was established by open surgery, histology and bacteriology. Chronic OM was proved in 14/20 lesions. Six of these 14 infections were located in peripheral areas without active bone marrow and 8/14 in central areas with active bone marrow. In peripheral OM, 5/6 with HIG and 6/6 with MAB were true positives. In the central skeleton all 8/8 infections appeared as cold lesions in the MAB study, which were defined as being false negative due to their non-specificity. Using HIG, 5/8 central infections were determined to be truly positive by showing photon-rich lesions. These 5 lesions were located in the hip region and in the pelvis, whereas 3 lesions of the spine were missed. There were no false-positive results in either studies. In conclusion, MAB was superior to HIG in peripheral OM concerning sensitivity, anatomical landmarks and differentiation of soft tissue versus bone infection. In central OM MAB detected all lesions accurately, but no differential diagnosis was possible due to the non-specificity of photon-low areas. In this respect HIG seems to be more specific due to the increased accumulation even in central infection sites.

Adult↗

Comparison of the accumulation and efflux kinetics of technetium-99m sestamibi and technetium-99m tetrofosmin in an MRP-expressing tumour cell line.

The potential clinical use of technetium-99m labeled sestamibi (Tc-MIBI) and tetrofosmin (Tc-Tfos) to image tumours is currently being evaluated. In this study. the accumulation and efflux of Tc-MIBI and Tc-Tfos in the nasopharyngeal carcinoma cell line CNE-1 were examined in the presence or absence of various inhibitors of P-glycoprotein (PGP) and/or multidrug resistance associated protein (MRP) activity [GG918, PSC833, verapamil (Vrp), cyclosporin A (CsA) and buthionine sulfoximine (BSO)]. Reverse-transcriptase polymerase chain reaction analysis and immunodetection of the CNE-1 cells detected expression of MRP, MRPI and MRP2 but not PGP. Tc-MIBI and Tc-Tfos accumulation was increased (P < 0.0001) and efflux decreased (P < 0.05) in the presence of BSO, CsA, Vrp and PSC833 but not GG918, which is a specific inhibitor of PGP. The absolute accumulation of Tc-MIBI was approximately twofold higher than that seen with Tc-Tfos, whereas the addition of inhibitors caused a much greater suppression of Tc-Tfos transport (>2 times greater than for Tc-MIBI). However, no qualitative differences in inhibitors were seen between Tc-MIBI and Tc-Tfos. These results suggest that both Tc-MIBI and Tc-Tfos are substrates for the MRP transporter and that PSC833, Vrp, CsA and BSO but not GG918 can inhibit MRP activity. These results indicate that Tc-MIBI and Tc-Tfos may be suitable imaging agents for detecting MRP-mediated drug resistance in human cancers.

ATP Binding Cassette Transporter, Subfamily B↗

Extraction and retention of technetium-99m Q12, technetium-99m sestamibi, and thallium-201 in isolated rat heart during coronary acidemia.

Technetium-99m Q12 and 99mTc-sestamibi are cationic lipophilic myocardial perfusion imaging tracers. Because myocardium in areas of ischemia becomes acidotic, experiments were designed to differentiate the effects of myocardial perfusate pH on radiotracer extraction and retention independent of substrate availability. We hypothesized that 99mTc-Q12 and 99mTc-sestamibi single-pass uptake and retention would be unaffected by a modest reduction in coronary perfusate pH. Isolated rat hearts were perfused at constant flow with Krebs-Henseleit buffer enriched with bovine red blood cells (20%). The indicator dilution method was used to measure the maximum extraction (Emax) and net extraction (Enet) of thallium-201 and 99mTc-Q12 (n = 8) or 201Tl and 99mTc sestamibi (n = 7) during baseline perfusion (pH = 7.4), during acidemic (pH = 6.7) perfusion, and during a restitution period with normal perfusate (pH = 7.4). 201Tl Emax (0.71+/-0.03) was greater than either 99mTc-Q12 or 99mTc-sestamibi Emax (0.27+/-0.02 and 0.26+/-0.01 respectively, P<0.0001). Acidemia significantly reduced 201Tl Emax (0.65+/-0.03, P<0.02) but not 99mTc-Q12 or 99mTc-sestamibi Emax (0.25+/-0.02 and 0.24+/-0.02 respectively). During control perfusion Enet of 201Tl was greater than that of 99mTc-Q12 at 3 and 5 min and greater than that of 99mTc-sestamibi at 3 min. 99mTc-Q12 Enet was less than 99mTc-sestamibi Enet at 3, 5, and 10 min. Acidemia decreased 201Tl and 99mTc-sestamibi Enet at 3, 5, and 10 min but had no effect on 99mTc-Q12 Enet. It is concluded that Emax of 99mTc-Q12 is less than that of 201Tl but is not different from that of 99mTc-sestamibi. Enet of 99mTc-Q12 is less than that of 99mTc-sestamibi.

Acidosis↗

Comparative myocardial uptake of technetium-99 m sestamibi and technetium-99m tetrofosmin one hour after stress injection.

Technetium-99m sestamibi and 99mTc-tetrofosmin are at present the preferred tracers for simultaneous assessment of myocardial perfusion and function by gated single-photon emission tomography (SPET). The aim of this work was to compare sestamibi and tetrofosmin myocardial uptake 1 h after stress injection. Consecutive unselected patients were studied either with sestamibi or with tetrofosmin on a random basis, until at least 100 patients had been enrolled for each gender and tracer. Stress was obtained by dipyridamole or exercise or combined dipyridamole + exercise; in the latter cases, exercise was sustained for at least 1.5 min after tracer injection. Injected activity was similarly adjusted to body weight. For each patient, imaging began 60-75 min after injection. All SPET projections were summed; due to the acquisition technology ("roving zoom", i.e. a mobile zoom), the heart always appeared at the centre of the frame in all projections and in the sum image. Thus minimal lung background contamination could be assumed in an elliptic region of interest placed over the heart on the sum image. Three indexes were analysed: total myocardial counts (Sum), mean myocardial pixel (Mean) and maximum myocardial pixel (Max). Four patient groups were analysed: males with sestamibi or tetrofosmin (MS: n = 189 and MT: n = 157), females with sestamibi or tetrofosmin (FS: n = 101 and FT: n = 104). MS and MT groups were comparable for physical variables, maximum heart rate and stress type, as were the FS and FT groups. Sum, Mean and Max were significantly higher with sestamibi (P = 0.0001 by ANOVA). Comparing MS vs MT and FS vs FT, mean values +/- SD were as follows: for Sum (kcounts) 750+/-184 vs 652+/-166, and 707+/-202 vs 594+/-189; for Mean (counts) 4517+/-1171 vs 4107+/-898, and 4908+/-1119 vs 4144+/-1025; and for Max (counts) 6471+/-1654 vs 5794+/-1312, and 7318+/-1886 vs 6152+/-1684. The mean gain with sestamibi was +15%, +10% and +12% in males, and +19%, +18% and +19% in females. Similar differences were found within each stress type subgroup. No gender-specific effect was found for Mean, so the overall mean gain was calculated for Mean: +13% for sestamibi vs tetrofosmin. These findings are consistent with other published smaller sample series. Possible differences between tracers with regard to residual activity in syringes were ruled out by an additional experiment. In summary, we found significantly higher myocardial counts with sestamibi than with tetrofosmin, in males as well as in females.

Adult↗

Direct comparison of technetium 99m-sestamibi and technetium 99m-tetrofosmin cardiac single photon emission computed tomography in patients with coronary artery disease.

BACKGROUND: Technetium 99m-labeled sestamibi and tetrofosmin tomography have shown high diagnostic accuracy in the detection of coronary artery disease (CAD). However, few data are available comparing sestamibi and tetrofosmin imaging in the same patients. The aim of the study was to determine the image quality of the two tracers and to compare the results of exercise sestamibi and tetrofosmin tomography in the same patients. METHODS: The results of exercise-rest sestamibi and tetrofosmin myocardial tomography were compared in 32 patients with suspected or known CAD who underwent coronary angiography. Image quality was evaluated subjectively. Regional tracer distribution was visually assessed and quantitatively measured in 22 segments/patient. RESULTS: At coronary angiography, 7 patients had normal coronary vessels, 11 single-vessel, and 14 multivessel CAD (> or =50% luminal stenosis). Image quality judged visually was comparable with the two tracers. Heart/lung and heart/liver ratios for sestamibi and tetrofosmin were not different. At visual analysis, 68% of the patients with CAD had abnormal findings with sestamibi and 76% with tetrofosmin (p = NS). At quantitative analysis, 92% of the patients with CAD had abnormal findings with sestamibi and 96% with tetrofosmin (p = NS). At both visual and quantitative analyses, sensitivity, specificity, and diagnostic accuracy in the detection of individual stenosed vessels were not different between the two tracers. Moreover, for both tracers sensitivity, specificity, and diagnostic accuracy in the detection of diseased vessels were significantly higher (all p < 0.05) at quantitative compared with visual analysis. Finally, defect size and severity were similar for the two tracers. CONCLUSIONS: Exercise-rest sestamibi and tetrofosmin tomography yielded images of comparable quality and provided similar results in the identification of patients with CAD and in the detection of the individual stenosed coronary vessels.

Adult↗

Mixed-ligand technetium(III) complexes with tetradendate/monodendate NS(3)/isocyanide coordination: a new nonpolar technetium chelate system for the design of neutral and lipophilic complexes stable in vivo.

Starting from the tripodal ligand 2,2',2' '-nitrilotris(ethanethiol) (NS(3)) and isocyanides (CNR) as co-ligands, neutral mixed-ligand technetium(III) complexes of the general formulation [Tc(NS(3))(CNR)] have been synthesized and characterized. The (99)Tc complexes can be( )()obtained by a two-step reduction/substitution procedure starting from [TcO(4)](-) via the phosphine-containing precursor complex [Tc(NS(3))(PMe(2)Ph)]. As shown by X-ray structural analyses, the complexes adopt a nearly ideal trigonal-bipyramidal geometry with the trigonal plane formed by the three thiolate sulfurs of the tripodal ligand. The central nitrogen atom of the chelate ligand and the monodendate isocyanides occupy the apical positions. The no-carrier-added preparation of the corresponding (99m)Tc complexes was performed by a one-step procedure starting from (99m)[TcO(4)](-) with stannous chloride as reducing agent. Biodistribution studies in the rat demonstrated for the nonpolar, lipophilic compounds a significant initial brain uptake. In vitro challenge experiments with glutathione clearly indicated that no transchelation reaction occurs. Furthermore, there were no indications for reoxidation of Tc(III) to Tc(V) species or pertechnetate. We propose this type of complexes as a useful tool in the design of lipophilic (99m)Tc or (186)Re/(188)Re radiopharmaceuticals.

Animals↗

Technetium-99m N,N'-bis(2-mercapto-2-methylpropyl)-2-aminobenzylamine: technetium-99m complexes of a novel bis(aminoethanethiol) ligand.

A new N2S2 ligand system, N,N'-bis(2-mercapto-2-methylpropyl)-2- aminobenzylamine, U-BAT, 1, containing uneven amine groups (two amine groups with different pKa values) for complexing [TcVO]3+, was prepared. The reaction of this novel ligand with [99mTc]pertechnetate, in the presence of stannous tartrate as the reducing agent, produces the neutral and lipid-soluble [99mTc]TcVO(U-BAT), TcS2C15H23N2O, 2. However, when the same reaction was carried out at a higher pH, 9-10, and with 30 min of heating (100 degrees C), a second neutral but more lipid-soluble complex, [99mTc]TcVO(OU-BAT), TcS2C15H21N2O, 3, was isolated. The X-ray crystallography data of the 99Tc complexes show square pyramidal coordination with N2S2 as the base and the Tc = O in the apical position. Compound 3 can be derived from 2 by an oxidation of the ligand to form an imine. After iv injection into rats, the neutral and lipid-soluble technetium-99m complexes showed significant brain uptake, 1.54 and 1.07% dose/organ at 2 min for [99mTc]TcVO(U-BAT) and TcVO(OU-BAT), respectively. The novel Tc chemistry of this new ligand system may provide a useful foundation for designing Tc complexes with a built-in redox mechanism.

Animals↗

Comparison of single-tracer (technetium-99m-sestamibi) and dual-tracer (thallium-201 chloride and technetium-99m-sestamibi) protocols for identification of myocardial ischemia.

BACKGROUND: The objective of this study was to determine if dual-tracer protocol using thallium-201 (201TI) chloride for rest and technetium-99m (99mTc)-sestamibi for stress images (TI-MIBI) detects ischemia better than single-tracer protocol using 99mTc-sestamibi for both rest and stress (MIBI) myocardial perfusion images. METHODS AND RESULTS: A total of 460 patients with suspected or known coronary artery disease (CAD) were included in the study, with 230 (50%) undergoing single-tracer MIBI protocol and 230 (50%) undergoing dual-tracer TI-MIBI protocol. Patient demographics were matched, and the proportion of patients having treadmill stress or dipyridamole stress was similar between the two groups. Stress and rest single photon emission computed tomographic images were recorded in all patients and dual-tracer 201TI and 99mTc-sestamibi (TI-MIBI) perfusion images were acquired separately. The scintigraphic images were analyzed visually, and a semiquantitative method of scoring reversible ischemia was used. Patients' reversibility scores in each group were compiled (ischemia index) and compared to determine the relative ability of each protocol in identifying ischemia. CONCLUSION: The frequency of ischemia and ischemia index was found to be significantly (P < 0.05) higher in the TI-MIBI group compared with the MIBI group. For detecting myocardial ischemia or viability, the dual-tracer TI-MIBI acquisition technique appears superior to the single-tracer MIBI protocol.

Coronary Circulation↗

Comparison between thallium-201, technetium-99m-sestamibi and technetium-99m-teboroxime planar myocardial perfusion imaging in detection of coronary artery disease.

Technetium-99m-sestamibi (MIBI) and 99mTc-teboroxime (TEBO) are two new myocardial perfusion imaging agents. The purpose of this prospective study was to compare MIBI and TEBO to 201TI planar imaging. Eighteen patients with significant coronary artery disease on coronary angiogram were submitted to three treadmill stress tests performed within 3 mo and were imaged with the three radiopharmaceuticals as follows. 1. TI: 2.2 mCi, immediate and delayed views (4 hr later, 8 min/view). 2. TEBO: 15-20 mCi at stress (1 min/view) and a second injection was repeated 4 hr later at rest (20-25 mCi). 3. MIBI: 15-18 mCi at stress (8 min/view) and 1-4 days later, 15-18 mCi at rest. Patients achieved similar levels of exercise. A blinded reading was performed by three observers. The left ventricle was divided into three segments/view and ischemic/normal wall ratios were also determined. Segmental comparison showed an agreement in 85% (138/162) of the segments between TI and TEBO, in 92% (149/162) between TI and MIBI and in 84% (136/162) between MIBI and TEBO. Abnormal TI, MIBI and TEBO studies were seen in 16 (89%), 16 (89%) and 15 (83%) patients, respectively, detecting 77, 75 and 65 abnormal segments. Ischemic-to-normal wall ratios were 0.75 +/- 0.06, 0.73 +/- 0.08 and 0.78 +/- 0.08 for TI, MIBI and TEBO, respectively. In conclusion, although the biologic characteristics of these agents are different, this study showed a good correlation between them in detection of significant coronary artery disease (high pretest likelihood population).

Aged↗

Rapid preparation and quality control method for technetium-99m-2-methoxy isobutyl isonitrile (technetium-99m-sestamibi).

Technetium-99m-2-methoxy isobutyl isonitrile (99mTc-sestamibi) is a radiopharmaceutical that can be useful in the evaluation of patients with acute myocardial infarction. The current method for preparation requires a lengthy boiling water bath procedure and the recommended quality control procedure is cumbersome and time-consuming. Using a microwave oven, the heating time necessary to provide a labeling efficiency (averaging 97% for sestamibi-labeled with maximum allowable 99mTc activity and volume has been reduced to 10 sec. A new mini-paper chromatography (MPC) system has been developed to analyze the radiochemical purity of 99mTc-sestamibi involving a 1:1 chloroform/tetrahydrofuran developing solvent. The recommended thin-layer chromatography (TLC) system involving the use of an AI2O3-coated plate requires an average time for drying and development of 34.8 +/- 1.6 min (n = 58) to complete, whereas the new MPC system has an average developing time of 2.3 +/- 0.1 min (n = 26). For radiochemical purity values ranging from 71-99% (n = 31), the MPC and TLC methods correlated closely (r = 0.99) with a regression line of MPC% = 1.05 TLC%--5.75. The combined use of the microwave oven heating method and our quick quality control system will facilitate the rapid, emergency use of 99mTc-sestamibi and eliminate the need for advance preparation of multiple kits each day.

Chromatography, Paper↗