• 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.

• Journal of Yeungnam Medical Science
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• v.32 no.2
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• pp.138-142
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• 2015

L-thyroxine (LT4) withdrawal prior to radioactive iodine (RAI) ablation therapy is a commonly used method for successful treatment of patients with papillary thyroid cancer (PTC). However, a prolonged period of hypothyroidism induced by LT4 withdrawal is sometimes associated with impaired quality of life and cardiopulmonary dysfunction in PTC patients. Furthermore, LT4 withdrawal may have a trophic effect on residual cancer by means of increased thyrotropin. We report on 2 cases of metastatic PTC patients with malignant pleural effusion (MPE) whose disease showed rapid worsening after LT4 withdrawal and RAI therapy. The first case is a 65-year-old woman who had PTC with multiple distant metastases and MPE. During LT4 withdrawal for RAI therapy, MPE showed rapid worsening, and the patient required repetitive therapeutic thoracentesis. The second case is a 49-year-old woman with PTC who underwent 3 additional operations for cancer recurrence in the neck lymph nodes and 6 times of RAI treatments. While preparing for the $7^{th}$ RAI treatment by withdrawing LT4, she developed MPE which became progressively aggravated after RAI therapy. Both patients experienced increased pleural effusion during the LT4 withdrawal period and a rise in the thyroglobulin level was observed after RAI therapy. MPE was not controlled with therapeutic thoracentesis and pleurodesis. Eventually, both patients died of rapid disease progression after RAI therapy. In summary, LT4 withdrawal may have an adverse effect on metastatic PTC patients, particularly those with MPE.

• The Korean Journal of Nuclear Medicine
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• v.36 no.2
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• pp.102-109
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• 2002

Purpose : In gene therapy, tumor cells expressing the herpes simplex virus thymidine kinase are sensitive to prodrugs. Potential prodrugs IVDU and IVFRU were synthesized and radiolabeled with radioiodine for noninvasive imaging of herpes simplex virus type 1 gene expression. Material and Methods : 5-(2-trimethysilyl) vinyl-2'-deoxyuridine and 5-(2-trimethylsilyl)vinyl-2'-fluoro-2'-deoxyuridine, precursors of 5-(2--iodo)viny l-2'-deoxy uridine(IVDU) and 5-(2-iodo)-2'-vinyl-2'-deoxy-2'-fluororibofuranosyl uracil(IVFRU), were synthesized from reaction of trans-1-trimethylsillyl-2-tri-n-butylstannylethylene with 5-iodo-2'-deoxyuridine and 5-iodo-2'-fluoro-2'-deoxyuridine, respectively, on the condition of Pd catalyst. These precursors were separated from reaction mixture by silica gel column chromatography method. Each precursor was radioiodinated with radioiodine by mixing with ICI oxidizing agent. These radioiodinated compounds were purified with HPLC. Radiohalogen exchange has been shown to be effective for the synthesis of products with lower specific activity. Similarly, carrier-added and high specific activity products have been isolated in respectable radiochemical yields using ICI method. Results : Synthetic yield of precursors, IVDU and IVFRU were 43% and 18%, respectively. Radiochemical purity of both compunds was over 98%. Conclusion : We synthesized precursors of IVDU and IVFRU for monitoring of HSV1-tk gene expression. Radiotracers were radioiodinated with high radiolabeling yield by ICI method.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2369-2374
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• 2014

Background and Aim: Selumetinib is a promising and interesting targeted therapy agent as it may reverse radioiodine uptake in patients with radioiodine-refractory differentiated thyroid cancer. We conduct this metaanalysis to compare the efficacy and safety of selumetinib with current therapies in patients with advanced cancer. Methods: An electronic search was conducted using PubMed/ Medicine, EMBASE and Cochrane library databases. Statistical analyses were carried out using either random-effects or fixed-effects models according to the heterogeneity of eligible studies. Results: Six eligible trials involved 601 patients were identified. Compared with current therapies, treatment schedules with selumetinib did not improve progression free survival (hazard ratio, 0.91; 95%CI 0.70-1.17, P= 0.448), but did identify better clinical benefits (odds ratio, 1.24; 95%CI 0.69-2.24, P = 0.472) and less disease progression (hazard ratio, 0.72; 95%CI 0.51-1.00, P = 0.052) though its impact was not statistically significant. Sub-group analysis resulted in significantly improved progression free survival (hazard ratio, 0.61; 95%CI 0.49-0.57, P = 0.00), clinical benefits (odds ratio, 3.04; 95%CI 1.60-5.77, P = 0.001) and reduced disease progression (hazard ratio, 0.35; 95%CI 0.18-0.67, P = 0.001) in patients administrated selumetinib. Dermatitis acneiform (risk ratio, 9.775; 95%CI 3.143-30.395, P = 0.00) and peripheral edema (risk ratio, 2.371; 95%CI 1.690-3.327, P = 0.00) are the most frequently observed adverse effects associated with selumetinib. Conclusions: Compared with current chemotherapy, selumetinib has modest clinical activity as monotherapy in patients with advanced cancer, but combinations of selumetinib with cytotoxic agents in patients with BRAF or KRAS mutations hold great promise for cancer treatment. Dermatitis acneiform and peripheral edema are the most frequently observed adverse effects in patients with selumetinib.

• Journal of radiological science and technology
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• v.33 no.3
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• pp.269-276
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• 2010

This study attempts to propose ways to optimize and improve the period of hospitalization for the radioiodine treatment by calculating the dose rate of patients treated with high-dose radioiodine by distance and time slot. As a result, 24 hours after the patient was treated with 100 mCi high-dose iodine, the dose rate was attenuated to $1,035{\mu}Sv/hr$ at the navel, to $109{\mu}Sv/hr$ at 50 cm, and to $33{\mu}Sv/hr$ at 100 cm. 24 hours after the patient was treated with 150 mCi high-dose iodine, the dose rate was attenuated to $637{\mu}Sv/hr$ at the navel, to $100{\mu}Sv/hr$ at 50 cm, and to $40{\mu}Sv/hr$ at 100 cm. 24 hours after the patient was treated with 180 mCi high-dose iodine, the dose rate was attenuated to $1,251{\mu}Sv/hr$ at the navel, $140{\mu}Sv/hr$ at 50 cm, and to $56{\mu}Sv/hr$ at 100 cm. In light of the current criterion for discharge recommended by the US Nuclear Regulatory Commission being $70.4{\mu}Sv/hr$, the present study indicates earlier discharge is feasible by applying a new scheme. This suggests that the proposed scheme in this study will help to solve the problem of shortage of treatment beds with the increasing trend of patients with thyroid cancer taken into consideration.

• Korean Journal of Head & Neck Oncology
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• v.15 no.1
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• pp.46-51
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• 1999

Background: Total thyroidectomy and postoperative radiodiodine ablation therapy in differentiated thyroid carcinomas enhance the reliability of serum thyroglobulin(Tg) levels and radioiodine scan in detecting recurrence or distant metastasis. There have been, however, some limitations in using these methods under certain conditions. Recently, several reports have indicated that thyroid peroxidase(TPO) could be used as an alternative tumor marker. We aimed to estimate the significance of serum TPO levels in differentiated thyroid carcinoma. Materials and Methods: Forty-eight patients who had undergone total thyroidectomy due to papillary thyroid carcinomas and who had been followed-up for at least 3 years were classified into two groups: 27 patients without any evidence of recurrence in group 1; and 20 patients with recurrence or distant metastasis in group 2. All patients were examined by radioiodine scans. Serum Tg, TSH, antithyroglobulin antibody, and TPO were measured and the relationships were statistically analyzed. The sensitivity and specificity of $^{131}I$ scan, serum Tg, and serum TPO were evaluated. Results: Serum Tg levels were $3.81{\pm}5.16ng/mL$ in group 1 and $147.02{\pm}193.75ng/mL$ in group 2. Only 2 patients in group 1 showed Tg levels exceeding 10ng/mL. In contrast, 4 patients in group 2 were under 10ng/mL. Serum antithyroglobulin antibody and TSH levels showed no statistical difference between the two groups. In group 1, 16 patients showed negative serum TPO results, and 4 patients in group 2 showed negative results. There was no correlation among serum Tg levels, antithyroglobulin antibody titers, and serum TPO levels in each group. In group 2, 4 patients with negative serum Tg levels showed positive TPO results and positive whole body scans. Two cases with false negative $^{131}I$ scans showed positive serum TPO and Tg results. In 4 cases showing false negative serum TPO levels, serum Tg levels and $^{131}I$ scans were positive. Conclusion: Serum Tg levels, radioiodine scans, and serum TPO levels can be clinically used as complementary methods in the diagnosis of recurrent or metastatic thyroid carcinomas. Serum TPO levels may be helpful when other methods fail to detect recurrences or distant metastasis in highly suspected patients.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.187-194
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• 1999

Purpose : The aim of this study is to look for the possible efficacy of external irradiation for locally advanced papillary thyroid cancers (stage pT4 or Nl ). Methods and Materials : From August 1981 through September 1997, 91 Patients with locally advanced papillary thyroid cancers (stage pT4 or Nl ) have been treated with external irradiation and followed up at our clinic. All of the patients have been treated with surgical resection. After surgery, 23 patients received postoperative external irradiation with or without ablative radioiodine therapy, whereas the other 68 patients were treated with ablative radioiodine therapy alone. Distributions of sex, age, and stage were comparable in both irradiated and nonirradiated groups. Multivariate analysis of the influence by age, sex, stage, ablative radioiodine therapy and external irradiation on local control were peformed by using Cox's proportional hazard model. Results : Overall survival rates at 7 years were of no significant difference in both groups. There were $98.1\%$ for no RT group and $90\%$ for RT group (p=0.506). 5-year local control rates were significantly different, these were $95.2\%$ for RT group and $67.5\%$ for no RT group (p=0.0408). An analysis of the prognostic factors, age, sex, stage, and RAI were not significant variables, except for the external irradiation. Conclusion : Adjuvant postoperative external irradiation did not affect overall survival, but significantly improved local control in the patients with locally advanced papillary thyroid cancers (stage pT4 or lympy node involvement).

• Journal of Medicine and Life Science
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• v.19 no.3
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• pp.95-102
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• 2022

This retrospective study aimed to investigate whether there was a difference in the success rate of removal of residual thyroid tissue in patients with the same cutoff serum thyroglobulin (Tg) value-measured 2 weeks after thyroid hormone withdrawal (THW)-for different radioactive iodine (RAI) activities. We identified 132 patients with papillary thyroid cancer who were treated with total thyroidectomy and RAI therapy to evaluate the efficacy of three radioactivities of I-131: 1,110, 3,700, and 5,550 MBq. Serum Tg testing was performed 1 week before RAI treatment and 2 weeks after THW (pre-Tg); the cutoff pre-Tg level was below 10 ng/mL. Stimulated Tg levels were measured on the day of I-131 administration (off-Tg). After 6 months of treatment, we compared the groups for complete ablation, defined as no uptake on a diagnostic I-131 scan, stimulated Tg level of <1.0 ng/mL, and Tg antibody level of <100 ng/mL. Ninety-five patients (72.0%) achieved complete ablation, with 57.1% (8/14), 78.2% (68/87), and 61.3% (19/31) in the 1,110 MBq, 3,700 MBq, and 5,550 MBq groups, respectively. There was no significant difference in the complete ablation rates between the three groups. In the multivariate analysis, the off-Tg level was a significant predictor of complete ablation. RAI therapy with low radioactivity (1,110 MBq) seemed sufficient for ablation in patients with papillary thyroid cancer with a pre-Tg level below 10 ng/mL. The off-Tg level is a promising and useful predictor of complete ablation after initial RAI therapy.

• The Korean Journal of Nuclear Medicine
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• v.34 no.2
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• pp.107-118
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• 2000

Purpose: To evaluate the effectiveness of radioiodine treatment for metastatic thyroid carcinoma, we reviewed results of radioactive iodine treatment in patients with functional lung or bone metastases. Materials and Methods: Of 760 patients who were treated for differentiated thyroid cancer between 1984 and 1998, we detected pulmonary metastases and bone metastases in 76 patients (10.0%) and 20 patients (2.6%), respectively. Among them, we could evaluate the effectiveness of I-131 therapy in 53 patients with lung metastases and 15 patients with bone metastases. Results: Of 53 patients who received I-131 therapy with a mean cumulative dose of 26.2 GBq (1.1-84.4 GBq) for pulmonary metastases, metastatic lung lesions completely resolved in 19 patients (35.8%) and improved in 22 patients (41.5%). In 13 of 19 patients with complete remission of pulmonary metastases, the total accumulated dose of I-131 was less than 18.5 GBq. We found 43 sites of metastatic bone lesions in 15 patients with bone metastases. Of 29 lesions which received I-131 therapy, metastatic lesions improved in 14 sites (48.3%), but did not change or progress in 15 sites (51.7%) despite the I-131 therapy. Three lesions were completely cured with a combination treatment of surgery(${\pm}$ external radiotherapy) and I-131 therapy, and the other 11 lesions improved. Conclusion: Radioactive iodine treatment gives favorable results for pulmonary metastases. However, for bone metastases, there might be a need to use combination therapy including I-131 and surgery or external irradiation.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.6
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• pp.322-326
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• 2006

A low iodine diet (LID) for $1{\sim}2$ weeks is recommended for patients who undergoing radioiodine remnant ablation. However, the LID educations for patients are different among centers because there is no concrete recommendation for protocol of LID. In this investigation, we compared two representative types of LID protocols performed in several centers in Korea using urine iodine to creatinine ratio (urine I/Cr). Methods: From 2006, April to June, patients referred to our center for radioiodine remnant ablation of thyroid cancer from several local hospitals which had different LID protocols were included. We divided into two groups, stringent LID for 1week and less stringent LID for 2 weeks, then measured their urine I/Cr ratio with spot urine when patients were admitted to the hospital. Results: Total 27 patients were included in this investigation (M:F=1:26; 13 in one-week stringent LID; 14 in two-week less stringent LID. Average of urine I/Cr ratio was $127.87{\pm}78.52{\mu}g/g$ in stringent LID for 1 week, and $289.75{\pm}188.24{\mu}g/g$ in less stringent LID for 2 weeks. It was significantly lower in stringent LID for 1 week group (p=0.008). The number of patients whose urine I/Cr ratios were below $100{\mu}g/g$ was 6 of 13 in stringent LID for 1 week group, and 3 of 14 in less stringent LID for 2 weeks group. Conclusion: Stringent LID for 1 week resulted in better urinary I/Cr ratio in our investigation compared with the other protocol. However it still resulted in plenty of inadequate range of I/Cr ratio, so more stringent protocol such as stringent LID for 2 weeks is expected more desirable.