• Radiation Oncology Journal
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• v.19 no.2
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• pp.118-126
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• 2001

Purpose : In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. Materials and Methods : From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was $48.2{\pm}7.9\;Gy$ in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at $4\~8$ weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. Results : An objective response was observed in 106 of 158 patients, giving a response rate of $67.1\%$. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only $29.2\%$ showed objective response in patients treated with dose less than 40 Gy, while $68.6\%\;and\;77.1\%$ showed major response in patients with $40\~50\;Gy$ and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Conclusion : Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver volume.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.2
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• pp.122-127
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• 2010

Purpose: The Xpress3.$cardiac^{TM}$ which is a kind of wide beam reconstruction (WBR) method developed by UltraSPECT (Haifa, Israel) enables the acquisition of at quarter time while maintaining image quality. The purpose of this study is to investigate the usefulness of WBR method for decreasing scan times and to compare to it with filtered back projection (FBP), which is the method routinely used. Materials and Methods: Phantom and clinical studies were performed. The anthropomorphic torso phantom was made on an equality with counts from patient's body. The Tl-201 concentrations in the compartments were 74 kBq (2 ${\mu}Ci$)/cc in myocardium, 11.1 kBq (0.3 ${\mu}Ci$)/cc in soft tissue, and 2.59 kBq (0.07 ${\mu}Ci$)/cc in lung. The non-gated Tl-201 myocardial perfusion SPECT data were acquired with the phantom. The former study was scanned for 50 seconds per frame with FBP method, and the latter study was acquired for 13 seconds per frame with WBR method. Using the Xeleris ver. 2.0551, full width at half maximum (FWHM) and average image contrast were compared. In clinical studies, we analyzed the 30 patients who were examined by Tl-201 gated myocardial perfusion SPECT in department of nuclear medicine at Asan Medical Center from January to April 2010. The patients were imaged at full time (50 second per frame) with FBP algorithm and again quarter-time (13 second per frame) with the WBR algorithm. Using the 4D MSPECT (4DM), Quantitative Perfusion SPECT (QPS), and Quantitative Gated SPECT (QGS) software, the summed stress score (SSS), summed rest score (SRS), summed difference score, end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) were analyzed for their correlations and statistical comparison by paired t-test. Results: As a result of the phantom study, the WBR method improved FWHM more than about 30% compared with FBP method (WBR data 5.47 mm, FBP data 7.07 mm). And the WBR method's average image contrast was also higher than FBP method's. However, in result of quantitative indices, SSS, SDS, SRS, EDV, ESV, EF, there were statistically significant differences from WBR and FBP(p<0.01). In the correlation of SSS, SDS, SRS, there were significant differences for WBR and FBP (0.18, 0.34, 0.08). But EDV, ESV, EF showed good correlation with WBR and FBP (0.88, 0.89, 0.71). Conclusion: From phantom study results, we confirmed that the WBR method reduces an acquisition time while improving an image quality compared with FBP method. However, we should consider significant differences in quantitative indices. And it needs to take an evaluation test to apply clinical study to find a cause of differences out between phantom and clinical results.

• 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.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.1
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• pp.9-15
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• 2007

Purpose: Repetitive transcranial magnetic stimulation (rTMS) has recently been clinically applied in the treatment of drug resistant depressed patients. There are mixed findings about the efficacy of rTMS on depression. Furthermore, the influence of rTMS on the physiology of the brain is not clear. We prospectively evaluated changes of regional cerebral blood flow (rCBF) between pre- and post-rTMS treatment in patients with drug resistant depression. Materials and Methods: Twelve patients with drug-resistant depression (7 male, 5 female; age range: $19{\sim}52$ years; mean age: $29.3{\pm}9.3$ years) were given rTMS on right prefrontal lobe with low frequency (1 Hz) and on left prefrontal lobe with high frequency (20 Hz), with 20-minute-duration each day for 3 weeks. Tc-99m ECD brain perfusion SPECT was obtained before and after rTMS treatment. The changes of cerebral perfusion were analyzed using statistical parametric mapping (SPM; t=3.14, uncorrected p<0.01, voxel=100). Results: Following areas showed significant increase in rCBF after 3 weeks rTMS treatment: the cingulate gyrus, fusiform gyrus of right temporal lobe, precuneus, and left lateral globus pallidus. Significant decrement was noted in: the precental and middle frontal gyrus of right frontal lobe, and fusiform gyrus of left occipital lobe. Conclusion: Low-frequency rTMS on the right prefrontal cortex and high-frequency rTMS on the left prefrontal cortex for 3 weeks as an add-on regimen have increased and decreased rCBF in the specific brain regions in drug-resistant depressed patients. Further analyses correlating clinical characteristics and treatment paradigm with functional imaging data may be helpful in clarifying the pathophysiology of drug-resistant depressed patients.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.4
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• pp.309-317
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• 2008

Objectives: The aim of this study was to evaluate the usefulness of Anti-mullerian hormone (AMH) as a predictive marker for ovarian response and cycle outcome in IVF cycles. Methods: From Jan., to Aug., 2007, 111 patients undergoing IVF/ICSI stimulated by short or antagonist protocol were selected. On cycle day 3, basal serum AMH level and FSH level were measured. The correlation between basal serum AMH or FSH, and COH outcome was analyzed and IVF outcome was compared according to the AMH levels. To determine the threshold value of AMH for poor- and hyper-response, ROC curve was analyzed. Results: Serum AMH showed higher correlation coefficient (r=0.792, p<0.001) with the number of retrieved mature oocyte than serum FSH (r=-0.477, p<0.001). According to ovarian response, FSH and AMH leves showed significant differences among poor, normal, and hyperresponder. For predicting poor (${\leq}2$ oocytes) and hyperresponse (${\geq}17$ oocyets), AMH cut-off values were 0.5 ng/ml (the sensitivity 88.9% and the specificity 89.5%) and 2.5 ng/ml (sensitivity 85.7%, specificity 87.0%), respectively. According to the AMH level, patients were divided into 3 groups: low (${\leq}0.60\;ng/ml$), normal ($0.60{\sim}2.60\;ng/ml$), and high AMH (${\geq}2.60\;ng/ml$). The number of retrieved mature oocytes was significantly higher ($2.7{\pm}2.2$, $8.1{\pm}4.8$, $16.5{\pm}5.7$) and total gonadotropin dose was lower ($3530.5{\pm}1251.0$, $2957.1{\pm}1057.6$, and $2219.2{\pm}751.9\;IU$) in high AMH group (p<0.001). There was no significant difference in fertilization rates and pregnancy rates (23.8%, 34.0%, 37.5%) among the groups. Conclusions: Basal serum AMH level correlated better with the number of retrieved mature oocytes than FSH level, suggesting its usefulness for predicting ovarian response. However, IVF outcome was not significantly different according to the AMH levels. Serum AMH level presented good cut-off value for poor- or hyper-responders, therefore it could be useful in prediction of cycle cancellation, gonadotropin dose, and OHSS risk in IVF cycles.

• Korean Journal of Agricultural Science
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• v.9 no.1
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• pp.284-302
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• 1982

Development of protein resources as food has been a big issue especially in Southeast Asia region, and intake of protein is also insufficient in Korea. To cope with this shortage of protein resources and its improvement together with increased production of high nutritive animal protein, studies were carried out on feeding of Korean native goats. In the experiments were made absorption of carbohydrate and volatile fatty acid in miniature rumen, and absorption of amino acid in rumen as in vivo were conducted as part of studies on nutritional absorption in rumen. Those nutritional for improvement of feeding and management as described above are summarized as following. 1. According to the result of test on the nutritional absorption of native goat by means of miniature rumen method, absorption ratio of VFA measured at 0.5, 1 and 2 hours after injection of nutrition showed propionic acid 70-86%, acetic acid 74-87%, and lactic acid 76-89%. In the absorption of organic substances, ethyl alcohol of 0.5% showed 29-87% and lactic acid of 0.1M showed 12-27% of absorption ratio. 2. Result of absorption measurement in rumen from L-type free amino acid injection in the content of rumen vein showed lower rate at menthionine-free group compared to whole-egg amino acid injection in the content of rumen vein showed lower rate at methioine-free group compared to whole-egg amino acid group, and high absorption ratio was observed at methionine 3 times group and urea added group. Deficiency of methionine caused no change of the content in mucous membranes. 3. Absorption of amino acid in rumen muscular layer showed equal tendency as in the mucous membrane without exerting any influence of methionine deficiency. At the methionine3-times group, content of methionine and glutamine were increased by 14.7 and 4.4 times as compared to whole-egg amino acid group, an absorption ratio of glutamine, proline and valine were increased at urea added group. 4. In general, concentration of amino acid in rumen vein plasma was lower than in rumen mucous membrane and muscular layer. Absorption ratio of amino acid is decreased due to methionine deficiency, and tripling of methionine or urea adding caused increment of amino acid. Absorption pattern is thus varied depending on the composition of amino acid. 5. At the urea added group, content of ammonia-N, amino-N and urea were increased in rumen muscular layer. As the inside of goat's rumen was unable to clean thoroughly, investigation was made on remaining bacteria, however, variation of ammonia-N was affected by these bacterial content. 6. Variation in rumen structure by differential absorption of amino acid was observed by general microscope and fluorescent microscope. According to the result of observation in the methionine 3 times group, single cylinder epithelium of mucous membrane showed rather thin, and it was thick at urea added group though no significant differences existed among test groups in submucous membrane and muscular layer.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.103-110
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• 1994

To find out the predictors of nocturnal arterial oxygen desaturation in patients with respiratory diseases, transcutaneous oxygen saturation($StcO_2$) monitoring studies using a pulse oximeter were performed during sleep in 20 patients. $StcO_2$ was decreased more than 4% from the baseline value in 18 patients(90%) and more than 10%("Desaturator") in 8(40%). Five of the seven patients(71.4%) with awake $PaO_2$<60mmHg and three of the thirteen patients(23.1%) with awake $PaO_2{\geq}60mmHg$ were "desaturators". The awake $PaO_2/FIO_2$ and $PaO_2/PAO_2$ could distinguish "desaturator" from "nondesaturator", and $PaO_2,\;SaO_2$ or $StcO_2$ could not. These results suggest that the nocturnal oxygen desaturation depends on the severity of the underlying disease rather than the baseline $PaO_2$. Anthropomorphic and lung function factors could not separate between "desaturator" and "non-desaturator", and about a quater of patients with a wake $PaO_2{\geq}60mmHg$ developed significant desaturation. Therefore, it is necessary to monitor the nocturnal arterial oxygen saturation in patients with respiratory diseases regardless of their severity of airflow obstruction or awake $PaO_2$.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.113-119
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• 1999

Purpose : To evaluate possible acute toxicity and early response of concurrent radiation therapy and low dose daily cisplatin as a radiosensitizer in patients with locally advanced uterine cervical carcinomas. Materials and Method : From December 1996 to January 1999, 38 previously untreated Patients with locally advanced squamous cell carcinoma of the uterine cervix (from stage IIB to stage IIIB) were treated at Inha University Hospital. All patients underwent standard pretreatment staging Procedures after the initial evaluation by gynecologists and radiation oncologists. Sixteen Patients with huge cervical mass (>4 cm) were submitted to the group treated with concurrent radiation therapy and low dose daily cisplatin while the remainder was treated with radiation therapy alone. Radiation therapy consisted of 4500 cGy external beam irradiation to whole pelvis (midline block after 3000 cGy), 900$\~$1000 cGy boost to involved parametrium, and high dose-rate intracavitary brachytherapy (a total dose of 3000$\~$3500 cGy/500 cGy per fraction to point A, twice per week). In the group treated with low dose cisplatin concurrently, 10 mg of daily intravenous cisplatin was given from the 1st day of radiation therapy to the 20th day of radiation therapy. Acute toxicity was measured according to expanded common toxicity criteria of the NCI (C) Clinical Trials. Early response data were analyzed at minimum 4 weeks' follow-up after completion of the treatment protocol. Results: Hematolgic toxici쇼 was more prominent in patients treated with radiation therapy and cisplatin. Six of 16 patients (37.5$\~$) treated with radiation therapy and cisplatin and one of 22 patients (4.5$\~$) treated with radiation therapy alone experienced grade 3 leukopenia. In Fisher's exact test, there was statistically significant difference between two groups regarding leukopenia (P=0.030). There was no apparent difference in the frequency of gastrointestinal and genitourinary toxicity between two groups (P=0.066). Three of 16 patients (18.7$\~$) treated with radiation therapy and cisplatin and two of 22 patients (9.1$\~$) treated with radiation therapy alone experienced more than 5 kg weight loss during the treatment. There was no statistically significant difference on weight loss between two groups (P=0.63). Two patients on each group were not evaluable for the early response because of incomplete treatment. The complete response rate at four weeks' follow-up was 80$\~$(16/20) for the radiation therapy alone group and 78$\~$ (11/14) for the radiation therapy and cisplatin group. There was no statistically significant difference in early response between two treatment groups (P=0.126). Conclusion : This study led to the conclusion that the hematologic toxicity from the treatment with concurrent radiation therapy and low dose daily cisplatin seems to be more prominent than that from the treatment of radiation therapy alone. There was no grade 4 hematologic toxicity or mortality in both groups. The hematologic toxicity in both treatment groups seems to be well managable modically. Since the risk factors were not balanced between two treatment groups, the direct comparison of early response of both groups was not possible. However, preliminary results regarding early response for patients with bulky cervical tumor mass treated with radiation therapy and low dose daily cisplatin was encouraging. Longer follow-up is necessary to evaluate the survival data. A phase III study is needed to evaluate the efficacy of concurrent daily low dose cisplatin with radiation therapy in bulky cervical cancer.

• The Korean Journal of Nuclear Medicine
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• v.38 no.4
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• pp.300-305
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• 2004

Purpose: We underwent this study to evaluate the factors which influence labeling efficiency when modified in vivo erythrocyte labeling technique was used. Materials and methods: Thirty healthy volunteers (M:F=19:11, age:$25{\pm}2$ yrs) were enrolled in this study. Totally, two hundred ten samples were obtained from them. The 1 mg of stannous pyrophosphate was injected intravenously at the beginning of labeling. After suitable tinning time (5 min, 20 min, 35 min) passed by, blood (5 mL, 3 mL or 1 mL) was withdrawn into 10 mL syringe previously containing Tc-99m (740 MBq) and anticoagulant (heparin, ACD or CPDA) through 19-gauged scalp needle. The generator ingrowth time of Tc-99m was within 24 hrs in each case. The blood samples were placed on rotating invertor during incubation (10 min, 25 min, 40 min) but some of them were not. Immediately after the conclusion of incubation, the labeled blood specimens to analyze were centrifuged. and then %Unbound Tc-99m was calculated. Statical analysis was used paired T-test and one way ANOVA with SPSS 10.0. Results: The binding efficiency at 1 mL of blood volume was $73{\pm}32%,\;91{\pm}10%$ at 3 mL and $96{\pm}7%$ at 5 mL (p<0.01). The binding efficiency at 5 min of tinning time was $45{\pm}23%,\;98{\pm}6%$, at 20 min and $97{\pm}8%$ at 35 min (p<0.001). The binding efficiency at 10 min of incubation time was $96{\pm}7%,\;95{\pm}12%$ at 25 min and $98{\pm}3%$ at 40 min (p>0.05). The binding efficiency in case of using rotating invertor was $96{\pm}7%$ and the binding efficiency in case of not using it was $87{\pm}18%$ (p>0.05). There was no significant difference between them. In binding efficiency according to kinds of anticoagulants, ACD was $98{\pm}4%$, CPDA was $97{\pm}6%$ and heparin was $89{\pm}20%$ (p<0.001). Conclusion: When modified in vivo erythrocyte labeling technique is used with Tc-99m, the methods to obtain the highest labeling efficiency are as follow. The withdrawing blood volume should be over 3 mL, tinning time should be kept between 20 min and 35 min, and incubation time should be kept between 10 min and 40 min. ACD or CPDA have to be used as a anticoagulant except heparin and the blood samples should be placed on rotating invertor during incubation.

• 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.