• 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.

• Journal of Chest Surgery
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• v.38 no.5 s.250
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• pp.323-334
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• 2005

Background: Gene therapy is a new and promising option for the treatment of severe myocardial ischemia by therapeutic angiogenesis. The goal of this study was to elucidate the efficacy of therapeutic angiogenesis by using VEGF165 in large animals. Material and Method: Twenty-one pigs that underwent ligation of the distal left anterior descending coronary artery were randomly allocated to one of two treatments: intramyocardial injection of pCK-VEGF (VEGF) or intramyocardial injection of pCK-Null (Control). Injections were administered 30 days after ligation. Seven pigs died during the trial, but eight pigs from VEGF and six from Control survived. Echo-cardiography was performed on day 0 (preoperative) and on days 30 and 60 following coronary ligation. Gated myocardial single photon emission computed tomography imaging (SPECT) with $^{99m}Tc-labeled$ sestamibi was performed on days 30 and 60. Myocardial perfusion was assessed from the uptake of $^{99m}Tc-labeled$ sestamibi at rest. Global and regional myocardial function as well as post-infarction left ventricular remodeling were assessed from segmental wall thickening; left ventricular ejection fraction (EF); end systolic volume (ESV); and end diastolic volume (EDV) using gated SPECT and echocardiography. Myocardium of the ischemic border zone into which pCK plasmid vector had been injected was also sampled to assess micro-capillary density. Result: Micro-capillary density was significantly higher in the VEGF than in Control ($386\pm110/mm^{2}\;vs.\;291\pm127/mm^{2};\;p<0.001$). Segmental perfusion increased significantly from day 30 to day 60 after intramyocardial injection of plasmid vector in VEGF ($48.4\pm15.2\%\;vs.\;53.8\pm19.6\%;\;p<0.001$), while no significant change was observed in the Control ($45.1\pm17.0\%\;vs.\;43.4\pm17.7\%;\;p=0.186$). This resulted in a significant difference in the percentage changes between the two groups ($11.4\pm27.0\%\;increase\;vs.\;2.7\pm19.0\%\;decrease;\;p=0.003$). Segmental wall thickening increased significantly from day 30 to day 60 in both groups; the increments did not differ between groups. ESV measured using echocardiography increased significantly from day 0 to day 30 in VEGF ($22.9\pm9.9\;mL\;vs.\;32.3\pm9.1\;mL;\; p=0.006$) and in Control ($26.3\pm12.0\;mL\;vs.\;36.8\pm9.7\;mL;\;p=0.046$). EF decreased significantly in VEGF ($52.0\pm7.7\%\;vs.\;46.5\pm7.4\%;\;p=0.004$) and in Control ($48.2\pm9.2\%\;vs.\;41.6\pm10.0\%;\;p=0.028$). There was no significant change in EDV. The interval changes (days $30\~60$) of EF, ESV, and EDV did not differ significantly between groups both by gated SPECT and by echocardiography. Conclusion: Intramyocardial injection of pCK-VEGF165 induced therapeutic angiogenesis and improved myocardial perfusion. However, post-infarction remodeling and global myocardial function were not improved.

• The Korean Journal of Nuclear Medicine
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• v.32 no.2
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• pp.129-136
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• 1998

Purpose: Myocardial SPECT is an effective test for detecting coronary artery disease in the general population. But the diagnostic accuracy between sexes is not defined. The purpose of this study is to compare the diagnostic accuracy between males and females. Materials and Methods: One hundred and seventy seven male and 98 female patients who underwent myocardial SPECT within 1 month of coronary angiography were studied. Myocardial SPECTS were considered abnormal if fixed or reversible perfusion defects were detected. Stenosis severity of ${\geq}$ 50% luminal diameter reduction of any artery defined coronary artery disease (CAD). Results: Overall sensitivity for detection of CAD was 98% in men and 97% in women (p=not significant). However, specificities, accuracies, and positive predictive values (PPV) in men and women were 49% vs 31% (p<0.05), 81% vs 57% (p<0.01), 78% vs 48% (p<0.01), respectively. Diagnostic accuracies for detection of right coronary artery disease were not different in both sexes, however, accuracies for detection of left anterior descending artery disease and left circumflex artery disease were significantly lower in female (p<0.05). Conclusion: A significant difference of diagnostic accuracy between sexes, especially in LAD and LCx disease, was noted. Artifacts from breast attenuation might be a cause for the lower diagnostic accuracy in female.

• The Korean Journal of Nuclear Medicine
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• v.35 no.3
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• pp.117-124
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• 2001

Serum thyroglobulin measurement and I-131 whole-body scintigraphy (WBS) are well-established methods for the detection of recurrence in the follow-up of patients with thyroid carcinoma. However, inconsistent results are observed frequently, and these two methods are not always able to detect recurrence. In some patients, serum thyroglobulin level is elevated but the WBS is negative, because the recurrent tumor is too small and below the sensitivity of the diagnostic scan, or there is a dissociation between thyroglobulin synthesis and the iodine frapping mechanism. In such cases, various nuclear imaging methods including Tl-201 Tc-99m-sestamibi, and F-18-FDG PET can be used besides anatomical imaging methods. Among them, FDG PET localizes recurrent lesions in WBS-negative thyroid carcinoma with high accuracy. Several studies have suggested that empirical high-dose I-131 therapy resulted in a high rate of visualization in post-therapy scans with evidence of subsequent improvement. An important question is when to operate on patients with recurrent tumor. We believe that surgical removal is the best means of treatment for patients with localized persistent tumor, despite the high-dose I-131 therapy. with tumor in thyroid remnant, and with isolated recurrence in the lymph node, lung or bone. In addition, we recommend palliative resection of locally unresectable mass with subsequent treatment with high-dose I-131 therapy. Before I-131 therapy, the evaluation of sodium-iodide symporter expression in thyroid carcinoma can predict iodine uptake. Retinoic acid is known to induce redifferentiation, and to enhance I-131 uptake in thyroid carcinoma. Retinoic acid therapy may represent an alternative approach before high-dose I-131 therapy.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.6
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• pp.519-525
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• 2009

Purpose: F-18 fluorodeoxyglucose (FDG) uptake of myocardium is influenced by various factors. Increased glycolysis, and subsequent increased F-18 FDG uptake has been reported in ischemic cardiomyopathy. However, clinical significance of incidentally found myocardial F-18 FDG uptake has not been clarified. We retrospectively reviewed the degree and pattern of myocardial uptake in patients without history of ischemic heart disease who underwent torso F-18 FDG PET/CT for evaluation of neoplastic disease. Materials and Methods: From January 2005 to June 2009, 77 patients who underwent F-18 FDG PET/CT and Tc-99m sestamibi stress/rest SPECT within 3 months were enrolled. Results: Of 77 patients, 55 (71.4%) showed increased F-18 FDG uptake in the myocardium. In this population, 40 showed uniform uptake pattern, while 15 showed focal uptake. In patients with uniform uptake, 17 showed decreased uptake in the septum without perfusion defect on myocardial SPECT. Remaining 23 patients showed uniform uptake, with 1 reversible perfusion defect and 1 fixed perfusion defect. In 15 patients with focal uptake, 9 showed increased F-18 FDG uptake in the base, and only 1 of them showed reversible perfusion defect on myocardial SPECT. In the remaining 6 focal uptake group, 4 had reversible perfusion defect in the corresponding wall, and 1 had apical hypertrophy. Conclusion: We demonstrated that septal defect pattern and basal uptake pattern in the myocardium may represent normal variants. Focal myocardial uptake other than normal variants on oncologic torso F-18 FDG PET/CT with routine fasting protocol may suggest ischemic heart disease, thus further evaluation is warranted.

• The Korean Journal of Nuclear Medicine
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• v.39 no.4
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• pp.224-230
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• 2005

Purpose: The maximal elastance ($E_{max}$) of myocardium has been established as a reliable load-independent contractility index. Recently, we developed a noninvasive method to measure the regional contractility using gated myocardial SPECT and arterial tonometry data. In this study, we measured regional $E_{max}(rE_{max}$ in the patients who underwent coronary artery bypass graft surgery (CABG), and assessed its relationship with other variables. Materials and Methods: 21 patients (M:F=17:4, $58{\pm}12$ y) who underwent CABG were enrolled. $^{201}TI$ rest/dipyridamole stress $^{99m}Tc$-sestamibi gated SPECT were performed before and 3 months after CABG. For 15 myocardial regions, regional time-elastance curve was obtained using the pressure data of tonometry and the volume data of gated SPECT. To investigate the coupling with myocardial function, preoperative regional $E_{max}$ was compared with regional perfusion and systolic thickening. In addition, the correlation between $E_{max}$ and viability was assessed in dysfunctional segments (thickening <20% before CABG). The viability was defined as improvement of postoperative systolic thickening more than 10%. Results: Regional $E_{max}$ was slightly increased after CABG from $2.41{\pm}1.64 (pre)\;to\;2.78{\pm}1.83 (post)$ mmHg/ml. $E_{max}$ had weak correlation with perfusion and thickening (r=0.35, p<0.001). In the regions of preserved perfusion (${\geq}60%$), $E_{max}$ was $2.65{\pm}1.67$, while it was $1.30{\pm}1.24$ in the segments of decreased perfusion. With regard to thickening, $E_{max}$ was $3.01{\pm}1.92$ mmHg/ml for normal regions (thickening ${geq}40%$), $2.40{\pm}1.19$ mmHg/ml for mildly dysfunctional regions (<40% and ${\geq}20%$), and $1.13{\pm}0.89$ mmHg/ml for severely dysfunctional regions (<20%). $E_{max}$ was improved after CABG in both the viable (from $1.27{\pm}1.07\;to\;1.79{\pm}1.48$ mmHg/ml) and non-viable segments (from $0.97 {\pm}0.59\;to\;1.22{\pm}0.71$ mmHg/ml), but there was no correlation between $E_{max}$ and thickening improvements (r=0.007). Conclusions: Preoperative regional $E_{max}$ was relatively concordant with regional perfusion and systolic thickening on gated myocardial SPECT. In dysfunctional but viable segments, $E_{max}$ was improved after CABG, but showed no correlation with thickening improvement. As a load-independent contractility index of dysfunctional myocardial segments, we suggest that the regional $E_{max}$ could be an independent parameter in the assessment of myocardial function.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.6
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• pp.513-518
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• 2009

Purpose: Integration of the functional information of myocardial perfusion SPECT (MPS) and the morphoanatomical information of coronary CT angiography (CTA) may provide useful additional diagnostic information of the spatial relationship between perfusion defects and coronary stenosis. We studied to know the added value of three dimensional cardiac SPECT/CTA fusion imaging (fusion image) by comparing between fusion image and MPS. Materials and Methods: Forty-eight patients (M:F=26:22, Age: $63.3{\pm}10.4$ years) with a reversible perfusion defect on MPS (adenosine stress/rest SPECT with Tc-99m sestamibi or tetrofosmin) and CTA were included. Fusion images were molded and compared with the findings from the MPS. Invasive coronary angiography served as a reference standard for fusion image and MPS. Results: Total 144 coronary arteries in 48 patients were analyzed; Fusion image yielded the sensitivity, specificity, negative and positive predictive value for the detection of hemodynamically significant stenosis per coronary artery 82.5%, 79.3%, 76.7% and 84.6%, respectively. Respective values for the MPS were 68.8%, 70.7%, 62.1% and 76.4%. And fusion image also could detect more multi-vessel disease. Conclusion: Fused three dimensional volume-rendered SPECT/CTA imaging provides intuitive convincing information about hemodynamic relevant lesion and could improved diagnostic accuracy.

• Korean Journal of Head & Neck Oncology
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• v.25 no.2
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• pp.138-142
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• 2009

Introduction : Although bilateral exploration has been thought to be the standard therapeutic modality for primary hyperparathyroidism(pHPT) due to the admirable cure rate, questions have remained as to whether bilateral neck exploration for all patients with pHPT is needed because 80-85% of patients with pHPT have a single parathyroid adenoma. If the diseased parathyroid can be determined preoperatively, a directed and minimal operation is appropriate using the recent innovations of preoperative diagnosis and operation techniques for parathyroid diseases, the radio-guided parathyroid surgery(RGPS) is one of the standards. In especial, RGPS has been reported beneficial in special circumstances, such as in recurrent disease, ectopic parathyroid, and in mediastinal parathyroid. It can be also useful for the parathyroid disease in previously explored or irradiated neck. Material and Methods : We experienced 2 cases of pHPT successfully treated by RGPS in who previously underwent extensive neck dissection and concomitant external or internal radiotherapy. We adopted and modified the technique described by Dr. James Norman at the University of South Florida-the minimally invasive parathyroidectomy using intraoperative nuclear mapping with 99mTc-sestamibi scanning and radioactivity detection probe. Results : We acquired the successful results for these patients. Conclusion : RGPS is thought to be the alternative technique for the patients with prior central neck exploration and irradiation.