ABSTRACT
Background and Objectives@#Even though most of the thyroid cancer shows good prognosis, de-differentiated thyroid cancer is still refractory to conventional treatments. Recently, kinase inhibitors including multi-kinase and BRAF inhibitors are widely used for treatment of de-differentiated thyroid cancers, but resistant to single kinase inhibitor treatment eventually encountered. Therefore, combination therapy may have better therapeutic effect than single therapy for thyroid cancer. In this study, we evaluated therapeutic effect of multi-kinase and BRAF inhibitor combination to anaplastic thyroid cancer cell lines with and without BRAF mutation. @*Materials and Methods@#We used anaplastic thyroid cancer cell lines with BRAF V600E mutation (8505C) and with NRAS mutation (HTh7). Both cell lines were treated with various concentration of multi-kinase inhibitor (lenvatinib) and BRAF inhibitor (vemurafenib). And combination of various concentration of both kinase inhibitors were used to treat both cell lines. Cytotoxic effect was assessed with cell counting kit-8 and therapeutic effect of single kinase inhibitor therapy and the combination therapy was compared. @*Results@#Anti-proliferative effect of vemurafenib on 8505C BRAF V600E -mutated cells was demonstrated from 0.25 μM concentration. However, HTh7 cells with NRAS mutation represented drug resistance up to 4 μM of vemurafenib. In case of lenvatinib treatment as a multi-kinase inhibitor, 8505C and HTh7 cells showed decreased cell viability dose-dependent manner. Combination treatment with vemurafenib and lenvatinib showed synergistic cytotoxic effect in BRAF mutated 8505C cell line, even at lower concentrations. @*Conclusion@#Combination treatment with multi-kinase inhibitor and BRAF inhibitor showed promising therapeutic results in BRAF mutated anaplastic thyroid cancer cell line.
ABSTRACT
Background and Objectives@#The aim of this study was to determine the clinical effectiveness of parotid gland (PG) massage for the prevention of PG dysfunction after administration of radioiodine (I-131) therapy for treatment of differentiated thyroid cancer (DTC). @*Materials and Methods@#One hundred patients with DTC with planned high-dose I-131 therapy were enrolled in the clinical trial and randomized into two groups (massage and non-massage group). Serum amylase values were obtained before and 24 h after I-131 therapy, and salivary gland scintigraphy (SGS) were taken before and at eight months after the I-131 therapy. Additional SGS (addSGS) were taken when the patients complained symptoms related to salivary gland dysfunction. Questionnaire surveys were performed before and until two years after I-131 therapy. @*Results@#Ninety-five of 100 patients finished the study protocol. Changes in survey scores tended to be higher in the non-massage group. The non-massage group had more severe symptoms related to salivary gland dysfunction. Among 32 patients who underwent addSGS, 27 had normal 8-month SGS. Of these 27 patients, 18 (66.7%) had salivary gland dysfunction on the addSGS. Amylase values were significantly increased in patients with normal 8-month SGS but abnormal addSGS, as compared to patients who were normal on both 8-month SGS and addSGS (p=0.046). Amylase difference values were a significant predictor of abnormal addSGS (p=0.002). Conclusion: PG massage reduced symptoms related to salivary gland dysfunction. The PG massage may be helpful in preventing damage to salivary glands caused by I-131 therapy.
ABSTRACT
Background and Objectives@#The aim of this study was to determine the clinical effectiveness of parotid gland (PG) massage for the prevention of PG dysfunction after administration of radioiodine (I-131) therapy for treatment of differentiated thyroid cancer (DTC). @*Materials and Methods@#One hundred patients with DTC with planned high-dose I-131 therapy were enrolled in the clinical trial and randomized into two groups (massage and non-massage group). Serum amylase values were obtained before and 24 h after I-131 therapy, and salivary gland scintigraphy (SGS) were taken before and at eight months after the I-131 therapy. Additional SGS (addSGS) were taken when the patients complained symptoms related to salivary gland dysfunction. Questionnaire surveys were performed before and until two years after I-131 therapy. @*Results@#Ninety-five of 100 patients finished the study protocol. Changes in survey scores tended to be higher in the non-massage group. The non-massage group had more severe symptoms related to salivary gland dysfunction. Among 32 patients who underwent addSGS, 27 had normal 8-month SGS. Of these 27 patients, 18 (66.7%) had salivary gland dysfunction on the addSGS. Amylase values were significantly increased in patients with normal 8-month SGS but abnormal addSGS, as compared to patients who were normal on both 8-month SGS and addSGS (p=0.046). Amylase difference values were a significant predictor of abnormal addSGS (p=0.002). Conclusion: PG massage reduced symptoms related to salivary gland dysfunction. The PG massage may be helpful in preventing damage to salivary glands caused by I-131 therapy.
ABSTRACT
Brain tumors represent a diverse spectrum of histology, biology, prognosis, and treatment options. Although MRI remains the gold standard for morphological tumor characterization, positron emission tomography (PET) can play a critical role in evaluating disease status. This article focuses on the use of PET with radiolabeled glucose and amino acid analogs to aid in the diagnosis of tumors and differentiate between recurrent tumors and radiation necrosis. The most widely used tracer is ¹⁸F-fluorodeoxyglucose (FDG). Although the intensity of FDG uptake is clearly associated with tumor grade, the exact role of FDG PET imaging remains debatable. Additionally, high uptake of FDG in normal grey matter limits its use in some low-grade tumors that may not be visualized. Because of their potential to overcome the limitation of FDG PET of brain tumors, 11C-methionine and ¹⁸F-3,4-dihydroxyphenylalanine (FDOPA) have been proposed. Low accumulation of amino acid tracers in normal brains allows the detection of low-grade gliomas and facilitates more precise tumor delineation. These amino acid tracers have higher sensitivity and specificity for detecting brain tumors and differentiating recurrent tumors from post-therapeutic changes. FDG and amino acid tracers may be complementary, and both may be required for assessment of an individual patient. Additional tracers for brain tumor imaging are currently under development. Combinations of different tracers might provide more in-depth information about tumor characteristics, and current limitations may thus be overcome in the near future. PET with various tracers including FDG, ¹¹C-methionine, and FDOPA has improved the management of patients with brain tumors. To evaluate the exact value of PET, however, additional prospective large sample studies are needed.
Subject(s)
Humans , Biology , Brain Neoplasms , Brain , Diagnosis , Electrons , Glioma , Glucose , Gray Matter , Magnetic Resonance Imaging , Necrosis , Positron-Emission Tomography , Prognosis , Prospective Studies , Radiopharmaceuticals , Sensitivity and SpecificityABSTRACT
Radioactive iodine (RAI) therapy for differentiated thyroid cancer has been successfully used for more than 70 years. However, there is still plenty of controversy surrounding the use and doses of radioiodine. There is insufficient evidence to answer the questions. Recent American Thyroid Association (ATA) guidelines seem to favor low-dose RAI, based on recent clinical trials and meta-analyses. However, long-term follow-up data remains limited, and there are additional factors we should consider that might affect the efficacy of RAI therapy. Therefore, until sufficient data are available, it is necessary to remain cautious about determining RAI doses by considering multiple patient-specific variables.
Subject(s)
Follow-Up Studies , Iodine , Thyroid Gland , Thyroid NeoplasmsABSTRACT
PURPOSE: Bisphosphonate (BP) is the first-line therapy for the management of osteoporosis. BP-related osteonecrosis of the jaw (BRONJ) and atypical femoral fracture (AFF) are increasingly common comorbidities in patients with osteoporosis under long-term BP treatment. The aim of this study was to evaluate the incidence and risk factors for AFF features on bone scintigraphy in patients with BRONJ.METHODS: Among total of 373 BRONJ patients treated between September 2005 and July 2014, 237 (220 women, 17 men; median age 73 years) who underwent three-phase bone scintigraphy were enrolled for this retrospective study. AFF features on bone scintigraphy and the related clinical factors were assessed.RESULTS: Among 237 patients with BRONJ, 11 (4.6%) showed AFF features on bone scintigraphy. BP medication duration (p = 0.049) correlated significantly with AFF features on bone scintigraphy in patients with BRONJ. BP intake duration of 34 months was the cutoff value for predicting the presence of AFF features on bone scintigraphy. Among the patients with BRONJ, all those with AFF features on bone scintigraphy were female patients with osteoporosis who were on oral BP medication; however, these factors were not significantly different along with AFF features on bone scintigraphy.CONCLUSIONS: The incidence of AFF features on bone scintigraphy was relatively high in patients with BRONJ. A careful observation of patients presenting with the AFF features on bone scintigraphy may be needed, particularly for female BRONJ patients with osteoporosis who have been on BP medication for over 34 months.
Subject(s)
Female , Humans , Male , Bisphosphonate-Associated Osteonecrosis of the Jaw , Comorbidity , Femoral Fractures , Incidence , Jaw , Osteonecrosis , Osteoporosis , Prevalence , Radionuclide Imaging , Retrospective Studies , Risk FactorsABSTRACT
Radioactive iodine (RAI) therapy for differentiated thyroid cancer has been successfully used for more than 70 years. However, there is still plenty of controversy surrounding the use and doses of radioiodine. There is insufficient evidence to answer the questions. Recent American Thyroid Association (ATA) guidelines seem to favor low-dose RAI, based on recent clinical trials and meta-analyses. However, long-term follow-up data remains limited, and there are additional factors we should consider that might affect the efficacy of RAI therapy. Therefore, until sufficient data are available, it is necessary to remain cautious about determining RAI doses by considering multiple patient-specific variables.
ABSTRACT
PURPOSE@#Bisphosphonate (BP) is the first-line therapy for the management of osteoporosis. BP-related osteonecrosis of the jaw (BRONJ) and atypical femoral fracture (AFF) are increasingly common comorbidities in patients with osteoporosis under long-term BP treatment. The aim of this study was to evaluate the incidence and risk factors for AFF features on bone scintigraphy in patients with BRONJ.@*METHODS@#Among total of 373 BRONJ patients treated between September 2005 and July 2014, 237 (220 women, 17 men; median age 73 years) who underwent three-phase bone scintigraphy were enrolled for this retrospective study. AFF features on bone scintigraphy and the related clinical factors were assessed.@*RESULTS@#Among 237 patients with BRONJ, 11 (4.6%) showed AFF features on bone scintigraphy. BP medication duration (p = 0.049) correlated significantly with AFF features on bone scintigraphy in patients with BRONJ. BP intake duration of 34 months was the cutoff value for predicting the presence of AFF features on bone scintigraphy. Among the patients with BRONJ, all those with AFF features on bone scintigraphy were female patients with osteoporosis who were on oral BP medication; however, these factors were not significantly different along with AFF features on bone scintigraphy.@*CONCLUSIONS@#The incidence of AFF features on bone scintigraphy was relatively high in patients with BRONJ. A careful observation of patients presenting with the AFF features on bone scintigraphy may be needed, particularly for female BRONJ patients with osteoporosis who have been on BP medication for over 34 months.
ABSTRACT
PURPOSE: Although Sjögren's syndrome (SS) is the most common disease causing xerostomia, autoimmune thyroid diseases can also affect the salivary glands. The aim of our study was to estimate the prevalence of thyroid diseases (TD) in subjects with symptoms of xerostomia and evaluate the efficacy of salivary gland scintigraphy (SGS) in the detection of TD in patients with SS and without SS.METHODS: We retrospectively reviewed the SGS findings of 173 subjects (men:women, 29:144) with symptoms of xerostomia. Ejection fractions (EF) in the parotid and submandibular glands were calculated. Thyroid disease was diagnosed on the basis of the results of the visual assessment of tracer uptake in the thyroid gland on SGS images as well as serological thyroid function tests.RESULTS: Based on the American-European Criteria, 94 patients were diagnosed with SS. Hashimoto's thyroiditis was diagnosed in 63 patients, subacute thyroiditis in 23, subclinical hypothyroidism in five, and Graves' disease in one. There were significant differences in the EF values of the parotid and submandibular glands between patients with TD and those with undetermined diagnoses.CONCLUSIONS: More than half of patients with xerostomia exhibited TD. Thyroid assessment by SGS is feasible, and SGS appears to be useful for the patients with xerostomia caused by TD. SGS may be the first imaging modality capable of evaluating both salivary gland function and thyroid gland status in patients with xerostomia. This strategy would make the requirement for additional workup for thyroid disease.
Subject(s)
Humans , Diagnosis , Graves Disease , Hypothyroidism , Prevalence , Radionuclide Imaging , Retrospective Studies , Salivary Glands , Submandibular Gland , Thyroid Diseases , Thyroid Function Tests , Thyroid Gland , Thyroiditis , Thyroiditis, Subacute , XerostomiaABSTRACT
BACKGROUND AND OBJECTIVES: The level of thyroid-stimulating hormone (TSH)-stimulated thyroglobulin (Tg) after thyroid hormone withdrawal (THW) is the most sensitive marker for detecting recurrence of differentiated thyroid cancer (DTC). In DTC, Tg production is regulated by TSH; however, TSH values after THW are never identical, even in the same patient. The objective of this study was to evaluate the influence of TSH on Tg levels after THW. MATERIALS AND METHODS: TSH and Tg concentrations were measured twice at 2 and 3 weeks after THW in 309 patients with DTC. TSH and Tg levels at these time points were compared. The percent change in TSH (ΔTSH) and change in Tg level (%ΔTg) from 2 to 3 weeks after THW were calculated, and Pearson's correlation coefficients were calculated to determine whether ΔTSH could affect %ΔTg. Tg cutoff value for diagnostic imaging was 2 ng/mL. RESULTS: The TSH and Tg values at 3 weeks were significantly higher than those at 2 weeks after THW. Tg values increased significantly to >2 ng/mL after 1 week in 38.5% of the patients with Tg values of 0.2-2 ng/mL at 2 weeks after THW. In patients with Tg values ≥2 ng/mL at 2 weeks after THW, Tg values increased significantly after an additional week of THW. ΔTSH correlated significantly with %ΔTg. CONCLUSION: TSH values differed according to time after THW, and Tg values differed significantly according to TSH values. Therefore, TSH values should be considered carefully when interpreting the meaning of Tg levels in patients with DTC.
Subject(s)
Humans , Diagnostic Imaging , Recurrence , Thyroglobulin , Thyroid Function Tests , Thyroid Gland , Thyroid Neoplasms , ThyrotropinABSTRACT
BACKGROUND AND OBJECTIVES: The aim of this study was to determine whether pathologically proven central or lateral lymph node (LN) metastasis (pN1a or pN1b) could affect ablation success and recurrence after high-dose radioactive iodine (RAI) ablation. We also sought to identify the risk factors for long-term recurrence in patients with papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: A total of 277 patients with pN1 disease who had undergone high-dose RAI ablation (5.55 GBq) between 2000 and 2006 were included in this retrospective study. We compared the ablation success rate and the recurrence rate between patients with pN1a and pN1b disease. Univariate and multivariate analyses were performed to identify the risk factors for recurrence. RESULTS: The median duration of follow-up was 10.2 years. The overall ablation success rate was 64%, and the ablation success rate in the pN1b group (49%) was lower than in the pN1a group (74%). The overall recurrence rate was 23%, and the recurrence rate in the pN1b group (30%) was higher than in pN1a group (18%). A higher ratio of metastatic LNs, a higher level of pre-ablation thyroglobulin, and ablation failure were significant risk factors for recurrence by multivariate analysis. CONCLUSION: Patients with pN1b disease experienced a lower ablation success rate and a higher recurrence rate than patients with pN1a disease. However, a higher ratio of metastatic LNs, a higher level of pre-ablation thyroglobulin, and ablation failure were stronger risk factors than the pathological N stage for long term recurrence in patients with node-positive PTC.
Subject(s)
Humans , Follow-Up Studies , Iodine , Lymph Nodes , Multivariate Analysis , Neoplasm Metastasis , Recurrence , Retrospective Studies , Risk Factors , Thyroglobulin , Thyroid NeoplasmsABSTRACT
BACKGROUND AND OBJECTIVES: The aim of this study was to determine whether pathologically proven central or lateral lymph node (LN) metastasis (pN1a or pN1b) could affect ablation success and recurrence after high-dose radioactive iodine (RAI) ablation. We also sought to identify the risk factors for long-term recurrence in patients with papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: A total of 277 patients with pN1 disease who had undergone high-dose RAI ablation (5.55 GBq) between 2000 and 2006 were included in this retrospective study. We compared the ablation success rate and the recurrence rate between patients with pN1a and pN1b disease. Univariate and multivariate analyses were performed to identify the risk factors for recurrence. RESULTS: The median duration of follow-up was 10.2 years. The overall ablation success rate was 64%, and the ablation success rate in the pN1b group (49%) was lower than in the pN1a group (74%). The overall recurrence rate was 23%, and the recurrence rate in the pN1b group (30%) was higher than in pN1a group (18%). A higher ratio of metastatic LNs, a higher level of pre-ablation thyroglobulin, and ablation failure were significant risk factors for recurrence by multivariate analysis. CONCLUSION: Patients with pN1b disease experienced a lower ablation success rate and a higher recurrence rate than patients with pN1a disease. However, a higher ratio of metastatic LNs, a higher level of pre-ablation thyroglobulin, and ablation failure were stronger risk factors than the pathological N stage for long term recurrence in patients with node-positive PTC.
Subject(s)
Humans , Follow-Up Studies , Iodine , Lymph Nodes , Multivariate Analysis , Neoplasm Metastasis , Recurrence , Retrospective Studies , Risk Factors , Thyroglobulin , Thyroid NeoplasmsABSTRACT
Primary meningeal melanomatosis is a rare, aggressive variant of primary malignant melanoma of the central nervous system, which arises from melanocytes within the leptomeninges and carries a poor prognosis. We report a case of primary meningeal melanomatosis in a 17-year-old man, which was diagnosed with 18F-fluorodeoxyglucose (F-18 FDG) PET/CT, and post hoc F-18 FDG PET/MRI fusion images. Whole-body F-18 FDG PET/CT was helpful in ruling out the extracranial origin of melanoma lesions, and in assessing the therapeutic response. Post hoc PET/MRI fusion images facilitated the correlation between PET and MRI images and demonstrated the hypermetabolic lesions more accurately than the unenhanced PET/CT images. Whole body F-18 FDG PET/CT and post hoc PET/MRI images might help clinicians determine the best therapeutic strategy for patients with primary meningeal melanomatosis.
Subject(s)
Adolescent , Humans , Male , Brain Neoplasms/diagnosis , Fluorodeoxyglucose F18 , Magnetic Resonance Imaging , Melanoma/diagnosis , Meningeal Neoplasms/diagnosis , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Whole Body ImagingABSTRACT
Melanoma can occur as a metastasis within subcutaneous tissue, lymph nodes, or viscera without a detectable primary tumor. Among patients with metastatic melanoma of unknown primary lesion, those with endobronchial metastasis are exceedingly rare. Herein we report a case of an endobronchial and pulmonary metastasis in a patient with melanoma originating from an unknown primary site. The patient without a previous history of melanoma presented with blood-tinged sputum. Fiberoptic bronchoscopy revealed a black polypoid tumor obstructing the posterior basal segmental bronchus of the right lower lobe. A final diagnosis of the malignant melanoma was made based on an immunohistochemical study of the bronchoscopic biopsy specimen. Skin, ophthalmic, oral, and nasal examinations failed to identify occult primary lesions. Subsequent evaluation including positron emission tomography/computed tomography scans did not uncover any abnormalities other than the metastatic pulmonary melanoma. We also describe the characteristic bronchoscopic features of melanoma.
Subject(s)
Humans , Biopsy , Bronchi , Bronchoscopy , Electrons , Lymph Nodes , Melanoma , Neoplasm Metastasis , Skin , Sputum , Subcutaneous Tissue , VisceraABSTRACT
PURPOSE: Early detection of recurrence is an important factor for long term survival of patients with colorectal cancer. Measurement of serum levels of CEA, CA 19-9, CT and PET/CT has been commonly used in the postoperative surveillance of colorectal cancer. The purpose of this study was to compare the diagnostic ability of PET/CT, tumor marker and CT for recurrence in colorectal cancer patients after treatment. MATERIALS AND METHODS: F-18 FDG PET/CT imaging was performed in 189 colorectal cancer patients who underwent curative surgical resection and/or chemotherapy. Measurement of serum levels of CEA, CA 19-9 and CT imaging were performed within 2 months of PET/CT examination. Final diagnosis of recurrence was made by biopsy, radiologic studies or clinical follow-up for 6 months after each study. RESULTS: Overall sensitivity, specificity of PET/CT was 94.7%, 91.1%, while those of serum CEA were 44.7% and 97.3%, respectively. Sensitivity and specificity were 94.2%, 90.4% for PET/CT and better than those of combined CEA and CA 19-9 measurement (52.1%, 88.5%) in 174 patients measured available both CEA and CA 19-9 data. In 115 patients with both tumor markers and CT images available, PET/CT showed similar sensitivity but higher specificity (92.9%, 91.3%) compared to combination of tumor markers and CT images (92.9%, 74.1%). CONCLUSION: PET/CT was superior for detection of recurred colorectal cancer patients compared with both CEA, CA 19-9, and even with combination of both tumor markers and CT. Therefore PET/CT could be used as a routine surveillance examination to detect recurrence or metastasis of colorectal cancer.
Subject(s)
Humans , Biopsy , Carcinoembryonic Antigen , Colorectal Neoplasms , Follow-Up Studies , Neoplasm Metastasis , Recurrence , Sensitivity and Specificity , Biomarkers, TumorABSTRACT
PURPOSE: To determine optimal imaging time for diagnostic I-123 whole body scan in the follow-up of patients with differentiated thyroid cancer (DTC), we compared the image quality of 6- and 24-hour images of the same subjects. MATERIALS AND METHODS: Four hundred ninety-eight patients (M:F=55:443, Age 47.6+/-12.9 years) with DTC who had undergone total thyroidectomy and I-131 ablation therapy underwent diagnostic whole body scanning 6 hour and 24 hour after oral ingestion of 185 MBq (5 mCi) of I-123. Serum thyroglobulin measurement and ultrasonography of the neck were performed at the time of imaging. In 40 patients underwent additional I-131 therapy, post-therapy I-131 images were obtained and compared with diagnostic I-123 images. RESULTS: In 440 patients (88.4%), 6- and 24-hour diagnostic I-123 images were concordant, and 58 patients (11.6%) showed discordant findings. Among 58 discordant patients, 31 patients showed abnormal tracer uptake on only 6-hour image, which turned out false-positive findings in all cases. In 12 patients with positive findings on only 24-hour image, remnant thyroid tissue (4 patients) and cervical lymph node metastasis (3 patients) were presented. Among 40 patients underwent additional I-131 therapy, 6-hour and 24-hour images were discordant in 13 patients. All 5 patients with abnormal uptake on only 6-hour image revealed false-positive results, whereas most of 24-hour images were concordant with post-therapy I-131 images. CONCLUSION: I-123 imaging at 24-hour could reduce false-positive findings and improve diagnostic accuracy, compared with 6-hour image in the follow-up of patient with DTC.
Subject(s)
Humans , Eating , Follow-Up Studies , Lymph Nodes , Neck , Neoplasm Metastasis , Thyroglobulin , Thyroid Gland , Thyroid Neoplasms , Thyroidectomy , Whole Body ImagingABSTRACT
PURPOSE: We have evaluated characteristics of adrenal masses incidentally observed in nonenhanced F-18 FDG PET/CT of the oncologic patients and the diagnostic ability of F-18 FDG PET/CT to differentiate malignant from benign adrenal masses. MATERIALS AND METHODS: Between Mar 2005 and Aug 2008, 75 oncologic patients (46 men, 29 women; mean age, 60.8+/-10.2 years; range, 35-87 years) with 89 adrenal masses incidentally found in PET/CT were enrolled in this study. For quantitative analysis, size (cm), Hounsfield unit (HU), maximum standardized uptake value (SUVmax), SUVratio of all 89 adrenal masses were measured. SUVmax of the adrenal mass divided by SUVliver, which is SUVmax of the segment 8, was defined as SUVratio. The final diagnosis of adrenal masses was based on pathologic confirmation, radiologic evaluation (HU<0 : benign), and clinical decision. RESULTS: Size, HU, SUVmax, and SUVratio were all significantly different between benign and malignant adrenal masses.(P < 0.05) And, SUVratio was the most accurate parameter. A cut-off value of 1.0 for SUVratio provided 90.9% sensitivity and 75.6% specificity. In small adrenal masses (1.5 cm or less), only SUVratio had statistically significant difference between benign and malignant adrenal masses. Similarly a cut-off value of 1.0 for SUVratio provided 80.0% sensitivity and 86.4% specificity. CONCLUSION: F-18 FDG PET/CT can offer more accurate information with quantitative analysis in differentiating malignant from benign adrenal masses incidentally observed in oncologic patients, compared to nonenhanced CT.
Subject(s)
Humans , Male , Adrenal Gland Neoplasms , Diagnosis, Differential , Neoplasm Metastasis , Sensitivity and SpecificityABSTRACT
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 ofiodide 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 I-131 was performed. In vivo nuclear imaging was obtained with gamma camera after I-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 I-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 I-131 cytotoxicity by AFP promoter, and the effect of the radioiodine therapy can be successfully assessed by non-invasive luminescence measurement.