• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.382-392
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• 2003

Purpose: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro and in vivo. Materials and Methods: Western blot analysis and immunohistochemistry were used for detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated at $100{\mu}M$ of verapamil (Vrp), $50{\mu}M$ of cyclosporin A (CsA) and $25{\mu}M$ of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 50 min at $37^{\circ}C$, using single cell suspensions at $1{\times}10^6cells/ml$. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of 370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). Results: Western blot analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549 cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin. Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629% and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI and tetrofosmin between Gr1 and Gr3. Percentage increases in MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively higher by the time up to 240 min with CsA. Conclusion: These results indicate that MIBI and tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators.

• The Korean Journal of Nuclear Medicine
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• v.30 no.1
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• pp.95-103
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• 1996

Reverse redistribution(RRD) refers to a perfusion defect that develops or becomes more evident on rest imaging compared with the stress imaging. This phenomenon was not uncommonly noted on myocardial perfusion single photon emission computed tomography (SPECT). However, the clinical significance and pathophysiological mechanism of RRD were unclear. The aim of this study was to evaluate the incidence and clinical significance of RRD on either dipyridamole T1-201 or Tc-99m MIBI myocardial perfusion SPECT. RRD was defined as ${\geq}10%$ decrease in relative T1-201 and Tc-99m MIBI uptakes on rest images compared to the stress images or as an appearance of new perfusion defects on rest images. It was observed in both T1-201 (44/463, 9.5%) and Tc-99m MIBI (124/999, 12.4%) myocardial SPECTs similarly, with an overall incidence of 11.5%(168/1462). Many apparent)y unrelated disease groups showed the finding: post-revascularization(53.9%), coronary artery disease(24.6%), myocardial infarction(12.3%), and those with normal coro-nary arteries (9.2%). Clinical and angiographic characteristics of 65 consecutive patients who underwent coronary arteriography in 168 patients who had RRD on myocardial perfusion SPECT were reviewed. Tc-99m MIBI was used in 44 patients, and T1-201 was used in 21 patients. Of the 81 myocardial segments analyzed which showed RRD, 32 segments(39.5%) were in septum, 24(29.5%) in inferior wallL, 12(14.8%) in anterior wall, 7(8.7%) in apex and 6(7.4%) in lateral wall. There was no clear association between RRD and coronary arterial stenosis or Presence of collateral circulations. Ventriculographical wall motion was evaluated in 27 regions with RRD; it was normal in 12 regions, hypokinetic in 12 regions and dyskinetic in 3 regions. In 14 of 21 patients who showed RRD on T1-201 myocardial SPECT, T1-201 reinjection was performed immediately after the 3-4 hour redistribution studies. Ten of 14 (71.4%) showed enhanced T1-201 activity(${\geq}10%$ increased) after reinjection. We conclude that RRD is not related to mode of stress or radiopharmaceuticals. RRD might represent many inhomogeneous pathophysiological processes.

• The Korean Journal of Nuclear Medicine
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• v.33 no.1
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• pp.40-48
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• 1999

Purpose: The sensitivity of ST-depression in the electrocardiogram during exercise is influenced by the level of efforts. However, unlike the prevalence of ST-depression on exercise ECG, the degree of exercise is reported to do not influence the diagnostic ability of myocardial perfusion scan. Furthermore, the relation between the prevalence of myocardial ischemia and effort is still controversial. We evaluated the effect of the degree of exercise on the ability of SPECT imaging to detect coronary artery stenosis. Materials and Methods: The patient population was comprised of 111 patients (73 men and 38 women, mean age 56 years) who underwent an exercise test in conjunction with Tc-99m MIBI and cardiac catheterization within 3 months apart each other. The degree of exercise was classified into four groups according to the percentage of maximal predicted heart rate. The sensitivity and specificity was compared between each group. Results: The overall diagnostic sensitivity was significantly higher with Tc-99m MIBI SPECT than exercise ECG. The specificity was not significantly different between two tests. Sensitivity and specificity of Tc-99m MIBI was not different between four groups. Sensitivity for individual coronary stenosis seemed to be lower in subjects who had premature termination of exercise due to early appearance of ST depression. Conclusion: These results suggest that the overall diagnostic sensitivity of Tc-99m MIBI myocardial perfusion SPECT is not significantly affected by the degree of exercise in stable patients undergoing symptom-limited treadmill exercise testing. Myocardial perfusion SPECT imaging should be added to routine exercise stress testing for the detection of coronary artery disease.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.1
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• pp.48-54
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• 2009

Purpose: There are few studies evaluating the usefulness of dedicated high-resolution scintimammography and no studies using delayed washout with this dedicated high resolution scintimammography for the evaluation of breast lesions. We underwent this study to evaluate the clinical usefulness of Tc-99m MIBI in evaluating patients with palpable breast lesions using dedicated high-resolution scintimammography. Materials and Methods: This study included 19 patients with 23 palpable breast lesions who underwent mammography. Tc-99m MIBI was taken to further characterize these lesions. Scintimammography images were acquired with standard craniocaudal and mediolateral oblique views and delayed images were additionally taken. Final conclusions were based on histopathology, either by biopsy or mastectomy results. Results: Eighteen lesions were malignant and five were benign. Mammography was indeterminate for thirteen lesions, nine of those were malignant. Mammography also categorized one lesion as benign in a dense breast, but scintimammography and pathology results showed malignancy. Of the five benign lesions, two were visible on scintimammography, but delayed images showed washout. Conclusion: Based on our preliminary results, dedicated high resolution scintimammography seems to be very useful in characterizing palpable lesions that were indeterminate or negative on mammography.

• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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• pp.59-64
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• 1993

To evaluate the usefulness and differences in diagnosing coronary artery disease (CAD) between men and women of intravenous dipyridamole $^{99m}Tc$-MIBI myocardial SPECT, we obtained $^{99m}Tc$-MIBI myocardial SPECT and compared with the findings of coronary angiographies. Ninety eight male and 37 female patients who underwent dipyridamole $^{99m}Tc$-MIBI myocardial imaging within one month of cardiac catheterization were studied. Scans were considered abnormal if perfusion defect was detected and the defect size was more than 12% for left anterior descending artery (LAD) and circumflex (LCX) and 8% for right coronary artery (RCA) territories. Lesions${\geqq}$50% luminal diameter narrowing were considered significant CAD. Overall sensitivity for detection of CAD was 94.3% in men and 96.4% in women; specificity was 70% in men and 52.6% in women (P=not significant, ns). Vessel-matched sensitivity was 75.3% in men and 72.7% in women (P=ns): specificity was 84.6% in men and 67.9% in women (P < 0.025). For individual coronary artery, the sensitivity in men and women was 87.7%, 81.8% for LAD; 78%, 83.3% for RCA and 52.2%, 46.7% for LCX (P=ns): the specificity was 80%, 40% for LAD (P<0.01), 82.5%, 68.4% for RCA, 88.9%, 86.4% for LCX (P=ns). The hemodynamic parameter after intravenous dipyridamole in men and women were significantly changed; the heart rate was increased and systolic, diastolic blood pressure was decreased. Adverse effects were reported in 58.8% of men and 72.7% in women (P=ns). The incidence of chest pain and headache were higher in women. There was no significant difference in the incidences of nausea, abdominal pain, dizziness, facial flushing, dyspnea. In conclusion, dipyridamole $^{99m}Tc$-MIBI myocardial SPECT is a safe, noninvasive test for evaluation of CAD. There was no gender difference to detect CAD, but more false-positive rate in women especially in the territory of LAD.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.85-98
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• 2004

Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.

• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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• pp.65-70
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• 1993

Among 64 patients with acute myocardial infarction who underwent coronary angiogrphy, 7 patients (10.9%) showed normal coronary artery. Six patients were men and 1 patient was female. The mean age of patients were $31.1{\pm}3.9$ years. Among the risk factors of coronary heart disease, smoking was most probable factor in patients with acute myocardial infarction with normal coronary angiography. $^{99m}Tc$-MIBI heart SPECT performed 5 of 7 patients and showed that it could be used in diagnosis, localization, extent of infarct area in patients with acute myocardial infarction with normal coronary angiograpy. But follow up $^{99m}Tc$-MIBI heart SPECT study will be needed to define the ability of myocardial viability in this patients.

• The Korean Journal of Nuclear Medicine
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• v.36 no.6
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• pp.325-332
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• 2002

Purpose: Human Na+/I- symporter (hNIS) is known to be expressed in many tissues other than thyroid gland. The breast cancer cells are one of them and the possibility of radioiodine therapy in treatment of the breast cancer may be suggested. We investigated the expression rate of hNIS and the relationship between the expression of hNIS and the finding of 99mTc-MIBI scintimammographv in the breast cancer Materials and Methods: Surgically proved 56 patients with breast cancer were the subjects of this study The expression of hNIS were evaluated by immunohistochemistry and the results were compared to the findings of 99m7c-MIBI scintimammography. Results: Overall expression rate of hNIS was 41.1% in 56 patients. According to the pathologic diagnosis, it was 42.9% in 49 patients with invasive ductal carcinoma and 28.6% in the 7 patients with ductal carcinoma in situ. The expression rate of hNIS in the 41 cases with a focal increased uptake at he breast lesion on 99m7c-MIBI sointimammogram was 31.7%. That in the 15 cases without any abnormal uptake on the scan was significantly higher(65.7%, p<0.05). Conclusion: The expression rate of hNIS in the patients with breast cancer was not so high. The rate was higher in the patients with no increased uptake at the breast lesion on 99m7c-MIBI scintimammography.

• Journal of Biomedical Engineering Research
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• v.16 no.2
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• pp.231-238
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• 1995

Tc-99m-MIBI (Sestamibi) myocardial SPECT along with TI-201 tomographic Imaging has demonstrated wide application and high image quality sufficient for the diagnosis of myocardial perfusion defect, which consequently reflects regional myocardial blood flow. The qualitative values of myocardial SPECT with Tc-99m-MIBI as well ds the quantitative cases depend in some degree on the reconstruction techniques of multiple projections. Filtered backprojection (FBP) Is the common standard method for reconstruction rather than the complicated and time-consuming arithmetic methods. In FBP it is known that the distribution of radioactivity in reconstructed transverse slices varies with the selected litter parameters such as cutoff frequencies and order (Butterworth case) The cutoff frequencies used in clinicAl practice partially remove and decrease the true radioactive distribution and alter the pixel counts, which lead to underestimation of true counts in specific myocardial regions. In this study, we have investigated the effect of cutoff frequencies of reconstruction filter on the artifactually induced perfusion defects, which are often demonstrated near inferior and/or inferoseptal cardiac walls due to the intense hepatic uptake of Tc-99m-MIBI. A computerized method for Identifying the relative degree of artifactual perfusion defect and for comparing those degrees along with the relative amount of hepatic uptake to myocardium was developed and patient images were studied to observe the quantitative degree of underestimation of myocardial perfusion, and to propose some reasonable threshold of cutoff frequency in the diagnosis of perfusion defect quantitatively. We concluded that from the quantitative viewpoint cutoff frequencies may be used as high as possible with the sacrifice of homogeneity of image quality, and those frequencies lower than the common 0.3 Wyquist frequency would reveal severe degradation of radioactive distribution near inferior and/or inferoseptal myocardium when applying Butterworth or low pass filter.

• Journal of Yeungnam Medical Science
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• v.16 no.1
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• pp.101-107
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• 1999

We evaluated the results of sequential SPECT dual-isotope imaging with Tl-201 and Tc-99m MIBI in 24 patients. all of whom also had coronary angiography within the past one month. Coronary angiography showed that 12 patients had no CAD, 4 patients had one-vessel CAD, 7 patients had two-vessel CAD and 1 patient had three-vessel CAD. Serial studies of resting Tl-201 and dipyridamole stress Tc-99m MIBI were completed within 2 hours. When more than 50% of coronary artery narrowing was considered significant, the overall sensitivity and specificity of CAD detection were 91.7%. The sensitivity of CAD detection in patients with one-vessel and multi-vessel diseases was 75% and 100%. respectively. Therefore, sequential dual-isotope SPECT demonstrated high sensitivity and specificity for CAD detection. In conclusion, sequential dual-isotope imaging is feasible and can be completed in a short time and may therefore enhance laboratory throughput and patient convenience.