• 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.

• Progress in Medical Physics
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• v.23 no.1
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• pp.15-25
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• 2012

The aim of this study is to evaluate plan quality and dose accuracy for Volumetric Modulated Arc Therapy (VMAT) on the TG-119 and is to investigate the effects on variation of the selectable optimization parameters of VMAT. VMAT treatment planning was implemented on a Varian iX linear accelerator with ARIA record and verify system (Varian Mecical System Palo Alto, CA) and Oncentra MasterPlan treatment planning system (Nucletron BV, Veenendaal, Netherlands). Plan quality and dosimetric accuracy were evaluated by effect of varying a number of arc, gantry spacing and delivery time for the test geometries provided in TG-119. Plan quality for the target and OAR was evaluated by the mean value and the standard deviation of the Dose Volume Histograms (DVHs). The ionization chamber and $Delta^{4PT}$ bi-planar diode array were used for the dose evaluation. For treatment planning evaluation, all structure sets closed to the goals in the case of single arc, except for the C-shape (hard), and all structure sets achieved the goals in the case of dual arc, except for C-shape (hard). For the variation of a number of arc, the simple structure such as a prostate did not have the difference between single arc and dual arc, whereas the complex structure such as a head and neck showed a superior result in the case of dual arc. The dose distribution with gantry spacing of $4^{\circ}$ was shown better plan quality than the gantry spacing of $6^{\circ}$, but was similar results compared with gantry spacing of $2^{\circ}$. For the verification of dose accuracy with single arc and dual arc, the mean value of a relative error between measured and calculated value were within 3% and 4% for point dose and confidence limit values, respectively. For the verification on dose accuracy with the gantry intervals of $2^{\circ}$, $4^{\circ}$ and $6^{\circ}$, the mean values of relative error were within 3% and 5% for point dose and confidence limit values, respectively. In the verification of dose distribution with $Delta^{4PT}$ bi-planar diode array, gamma passing rate was $98.72{\pm}1.52%$ and $98.3{\pm}1.5%$ for single arc and dual arc, respectively. The confidence limit values were within 4%. The smaller the gantry spacing, the more accuracy results were shown. In this study, we performed the VMAT QA based on TG-119 procedure, and demonstrated that all structure sets were satisfied with acceptance criteria. And also, the results for the selective optimization variables informed the importance of selection for the suitable variables according to the clinical cases.

• The Korean Journal of Nuclear Medicine Technology
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• v.17 no.1
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• pp.62-66
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• 2013

Purpose: I-131 is a radioisotope widely used for thyroid gland treatments. The physical half life is 8.01 and characterized by emitting beta and gamma rays which is used in clinical practice for the purpose of acquiring treatment and images. In order to reduce the recurrence rate after surgery in high-risk thyroid cancer patients, the remaining thyroid tissue is either removed or the I-131 is used for treatment during relapse. In cases of using a high dosage of radioactive iodine requiring hospitalization, the patient is administered dosage in the hospital isolation ward over a certain period of time preventing I-131 exposure to others. By checking the radiation amount emitted from patients before discharge, the patients are discharged after checking whether they meet the legal standards (50 uSv/h). After patients are discharged from the hospital, the contamination level is checked in many parts of the ward before the next patients are hospitalized and when necessary, decontamination operations are performed. It is expected that there is exposure to radiation when measuring the ward contamination level and dose check emitted from patients at the time of discharge whereby the radiation exposure by health workers that come from the patients in this process is the main factor. This study analyzed the correlation between discharge dose of patients and ward contamination level through a variety of factors such as renal functions, gender, age, dosage, etc.). Materials and Method: The study was conducted on 151 patients who received high-dosage radioactive iodine treatment at Soon Chun Hyang University Hospital during the period between 8/1/2011~5/31/2012 (Male: Female: 31:120, $47.5{\pm}11.9$, average dosage of $138{\pm}22.4$ mCi). As various factors expected to influence the patient discharge dose & ward contamination such as the beds, floors, bathroom floors, and washbasins, the patient renal function (GFR), age, gender, dosage, and the correlation between the expected Tg & Tg-Tb expected to reflect the remaining tissue in patients were analyzed. Results: In terms of the discharge dose and GFR, a low correlation was shown in the patient discharge dose as the GFR was higher (p < 0.0001). When comparing the group with a dosage of over 150mCi and the group with a lower dosage, the lower dosage group showed a significantly lower discharge dose ($24{\pm}10.4uSv/h$ vs $28.7{\pm}11.8uSv/h$, p<0.05). Age, gender, Tg, Tg-Tb did not show a significant relationship with discharge dose (p> 0.05). The contamination level in each spot of the treatment ward showed no significant relationship with GFR, Tg, Tg-Tb, age, gender, and dosage (p>0.05 ). Conclusion: This study says that discharge of the dose in the patient's body is low in GFR higher and Dosage 150mCi under lower. There was no case of contamination of the treatment ward, depending on the dose and renal association. This suggests that patients' lifestyles or be affected by a variety of other factors.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.1
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• pp.83-89
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• 2010

Purpose: The Wide Beam Reconstruction (WBR) algorithms that UltraSPECT, Ltd. (U.S) has provides solutions which improved image resolution by eliminating the effect of the line spread function by collimator and suppression of the noise. It controls the resolution and noise level automatically and yields unsurpassed image quality. The aim of this study is WBR of whole body bone scan in usefulness of clinical application. Materials and Methods: The standard line source and single photon emission computed tomography (SPECT) reconstructed spatial resolution measurements were performed on an INFINA (GE, Milwaukee, WI) gamma camera, equipped with low energy high resolution (LEHR) collimators. The total counts of line source measurements with 200 kcps and 300 kcps. The SPECT phantoms analyzed spatial resolution by the changing matrix size. Also a clinical evaluation study was performed with forty three patients, referred for bone scans. First group altered scan speed with 20 and 30 cm/min and dosage of 740 MBq (20 mCi) of $^{99m}Tc$-HDP administered but second group altered dosage of $^{99m}Tc$-HDP with 740 and 1,110 MBq (20 mCi and 30 mCi) in same scan speed. The acquired data was reconstructed using the typical clinical protocol in use and the WBR protocol. The patient's information was removed and a blind reading was done on each reconstruction method. For each reading, a questionnaire was completed in which the reader was asked to evaluate, on a scale of 1-5 point. Results: The result of planar WBR data improved resolution more than 10%. The Full-Width at Half-Maximum (FWHM) of WBR data improved about 16% (Standard: 8.45, WBR: 7.09). SPECT WBR data improved resolution more than about 50% and evaluate FWHM of WBR data (Standard: 3.52, WBR: 1.65). A clinical evaluation study, there was no statistically significant difference between the two method, which includes improvement of the bone to soft tissue ratio and the image resolution (first group p=0.07, second group p=0.458). Conclusion: The WBR method allows to shorten the acquisition time of bone scans while simultaneously providing improved image quality and to reduce the dosage of radiopharmaceuticals reducing radiation dose. Therefore, the WBR method can be applied to a wide range of clinical applications to provide clinical values as well as image quality.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.87-96
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• 1994

Background : Since tumor necrosis factor was discovered in 1975, TNF has been well known about its cytotoxic effect on tumor cells in vivo and in vitro. According to the recent improvement of molecular biological techinques, it is possible that exogenous TNF gene is transferred to tumor cells and is expressed in theirs. By virtue of TNF gene transfer, we have expected that TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells in vivo without systemic side effect. The expected mechanisms in which antitumor effects of TNF expressed in TNF-gene-transferred tumor cells are working would be as followings. In the first mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells around(like homicide). In the second mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill themselves(like suicide). In the third mechanism, TNF expressed in TNF-gene-transferred tumor cells would recruit immune effector cells and kill tumor cells indirectly. In the last mechanism, TNF expressed in TNF-gene-transferred tumor cells would augment cytokine such as interferon-$\gamma$ to kill tumor cells. Among these four mechanisms of antitumor effect, only the second mechanism has not been established yet. Therefore, to elucidate the second mechanism, We performed this study. Method : We transferred TNF-$\alpha$ gene to NCI-H2058, a human mesothelioma cell line and WEHI164, a murine fibrosarcoma cell line by using retroviral vector(pLT12SNTNF). And, We determined by using MTT assay whether TNF expressed in TNF-gene-transferred tumor cell lines would kill themselves like suicide or not. Then, if TNF-gene-transferred tumor cell lines would not suicide themselves, I would know more about the TNF sensitivity of TNF-gene-transferred tumor cell lines to exogenous TNF also by MTT assay. Result : NCI-H2058 and WEHI164 which were sensitive to TNF, became far less sensitive to endogenous and exogenous TNF after being transferred TNF-$\alpha$ gene to. Conclusion : TNF-gene-transfer to NCI-H2058 and WEHI164 gave them resistance to TNF.

• The Korean Journal of Nuclear Medicine
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• v.38 no.4
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• pp.294-299
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• 2004

Purpose: Both human NIS and mutant $D_2R$ transgenes are proposed as reporting system in transplanted cell tracking. Using hepatoma cell lines, we constructed a dual reporter system containing human sodium-iodide symporter (hNIS) and dopamine 2 receptor ($D_2R$) and compared its characteristics. Materials and Methods: The recombinant plasmid ($pIRES-hNIS/D_2R$) was constructed with IRES (internal ribosome entry site) under control of the CMV promoter $pIRES-hNIS/D_2R$ was transfected to human hepatoma SK-Hep1 cell line with lipofectamine. HEP-ND ($SK-Hep1-hNIS/D_2R$) cells stably expressing hNIS and $D_2R$ was established by selection with G418 for two weeks. RT-PCR was performed to investigate the expression of both hNIS and $D_2R$ genes. The expressions of hNIS and $D_2R$ were measured by $^{125}I$ uptake assays and receptor binding assays. Specific binding of $D_2R$ to $[^3H]spiperone$ was verified by Scatchard plot with (+) butaclamol as a specific inhibitor. $K_d\;and\;B_{max}$ values were estimated. The correlation between hNIS and $D_2R$ expression was compared by using each clone. Results: Similar quantities of hNIS and $D_2R$ genes were expressed on HEP-ND as RT-PCR assays. HEP-ND cells showed 30 to 40 fold higher radioiodine uptakes than those of parental SK-Hep1 cells. $^{125}I$ uptake in HEP-ND cells was completely inhibited by $KClO_4$, a NIS inhibitor Specific binding to HEP-ND cells was saturable and the $K_d\;and\;B_{max}$ values for HEP-ND cells were 2.92 nM, 745.25 fmol/mg protein and 2.91nM, 1323 fmole/mg protein in two clones, respectively. The radioiodine uptake by hNIS activity and $D_2R$ binding was highly correlated. Conclusion: We developed a dual positron and gamma imaging reporter system of hNIS and $D_2R$ in a stably transfected cell line. We expect that $D_2R$ and hNIS genes can complement mutually as a nuclear reporting system or that $D_2R$ can be used as reporter gene when hNIS gene were used as a treatment gene.

• 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.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.5
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• pp.383-393
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• 2008

Purpose: Cancer specific killing can be achieved by therapeutic gene activated by cancer specific promotor. Expression of sodium iodide symporter (NIS) gene causes transportation and concentration of iodide into the cell, therefore radioiodine treatment after NIS gene transfer to cancer cell could be a form of radionuclide gene therapy. luciferase (Luc) gene transfected cancer cell can be monitored by in vivo optical imaging after D-luciferin injection. Aims of the study are to make vector with both therapeutic NIS gene driven by AFP promoter and reporter Luc gene driven by CMV promoter, to perform hepatocellular carcinoma specific radiodiodine gene therapy by the vector, and assessment of the therapy effect by optical imaging using luciferase expression. Materials and Methods: A Vector with AFP promoter driven NIS gene and CMV promoter driven Luc gene (AFP-NIS-CMV-Luc) was constructed. Liver cancer cell (HepG2, Huh-7) and non liver cancer cell (HCT-15) were transfected with the vector using liposome. Expression of the NIS gene at mRNA level was elucidated by RT-PCR. Radioiodide uptake, perchlorate blockade, and washout tests were performed and bioluminescence also measured by luminometer in these cells. In vitro clonogenic assay with 1-131 was performed. In vivo nuclear imaging was obtained with gamma camera after 1-131 intraperitoneal injection. Results: A Vector with AFP-NIS-CMV-Luc was constructed and successfully transfected into HepG2, Huh-7 and HCT-15 cells. HepG2 and Huh-7 cells with AFP-NIS-CMV-Luc gene showed higher iodide uptake than non transfected cells and the higher iodide uptake was totally blocked by addition of perchlorate. HCT-15 cell did not showed any change of iodide uptake by the gene transfection. Transfected cells had higher light output than control cells. In vitro clonogenic assay, transfected HepG2 and Huh-7 cells showed lower colony count than non transfected HepG2 and Huh-7 cells, but transfected HCT-15 cell did not showed any difference than non transfected HCT-15 cell. Number of Huh-7 cells with AFP-NIS-CMV-Luc gene transfection was positively correlated with radioidine accumulation and luciferase activity. In vivo nuclear imaging with 1-131 was successful in AFP-NIS-CMV-Luc gene transfected Huh-7 cell xenograft on nude mouse. Conclusion: A Vector with AFP promoter driven NIS and CMV promoter driven Luc gene was constructed. Transfection of the vector showed liver cancer cell specific enhancement of 1-131 cytotoxicity by AFP promoter, and the effect of the radioiodine therapy can be successfully assessed by non-invasive luminescence measurement.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.331-338
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• 1995

Purpose : To evaluate our clinical experience with the combination of teletherapy and intraluminal brachytherapy in patients with unresectable or inoperable esophageal cancers. Materials and Methods : From Nov 1989 to Mar 1993, twenty patients with esophageal cancer were treated with radical radiotherapy and intraluminal brachytherapy at Yonsei Cancer Center. All patients had squamous histolgy and stage distribution was as follows: stage II, 4($20{\%}$)patients; III, 15 ($75{\%}$)patients; IV, 1($5{\%}$)patients. A dose of S-12Gy/1-3weeks with intraluminal brachytherapy (3-5Gy/fraction) to 5mm from the outside of the esophageal tube using high dose rate Iridium-192 remotely afterloading brachytherapy machine was given 2 weeks after a total dose of 59-64Gy with external radiotherapy. Induction chemotherapy using cisplatin and 5-FU was performed in 13 patients with median 3 cycles(1-6 cycles), Response rate, local control rate, survival and complications were analysed retrospectively. Results : Two-year overall survival rate and median survival were $15.8{\%}$ and 13.5 months. Response rates were as follows complete remission(CR) 5($25{\%}$): partial remission a(PRa) 7($35{\%}$): partial remission b(PRb) 7($35{\%}$), no response(NR) 1($5{\%}$). Patterns of failure were as follows; local failure 13($65{\%}$), local and distant failure 3($15{\%}$), distant failure 0($0{\%}$). Ultimate local control rate was $20{\%}$. Treatment related complications included esophageal ulcer in two patients and esophageal stricture in one. Conclusion : Though poor local conrol rate, median survival was improved as compared with previous results of radiation therapy alone(8months) and chemoradiation combined treatment(11 months) in Yonsei Cancer Center High-dose-rate intraluminal brachytherapy following external irradiation is an effective treatment modality with acceptable toxicity in esophageal cancer.

• Journal of Food Hygiene and Safety
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• v.27 no.3
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• pp.233-246
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• 2012

In this study, we investigated the applicability of the photostimulated luminescence(PSL), thermoluminescence(TL) and electron spin resonance(ESR) methods for various foods which are not allowed to be irradiated in Korea. All 15 foods including sesame, almond, peanut, cocoa powder etc. were analyzed. Samples were irradiated at 1~10 kGy using a $^{60}Co$ gamma-ray irradiator. In PSL study, the photon counts of all the unirradiated samples showed negative(lower than 700). The photon counts irradiated(1 kGy) dried shrimp, roasted peanut and seasoned peanut showed positive(higher than 5,000) and the other samples were negative or intermediate(> 700 and < 5,000). In TL analysis, results showed that it is possible to apply TL method to all foods containing minerals. In ESR measurements, the ESR signal(single-line) intensity of irradiated foods was higher than non-irradiated foods. In particular, the specific ESR signals of irradiation-induced crystalline sugar, cellulose and bone radical were detected in dried plum, raisin, dried cherry, mango(dried, frozen), rambutan, cocoa(powder), cinnamon, parsley, carrot, broccoli, dried arrow squid, dried pollack and dried shrimp. According to the results, PSL, TL and ESR methods were successfully applied to detect the irradiated foods because TL method is not able to detect the irradiated foods rarely composed of minerals. ESR is also a difficult method to detect the changes of ESR signal patterns of food. It is concluded that TL analysis or ESR assay is suitable for detection of irradiated samples and a combined method is recommendable for enhancing the reliability of detection results.