Sample records for hnis radioiodine gene

  1. Feasibility of dual reporter gene in rat myoblast cell line using human sodium iodide symporter (hNIS) and enhanced green fluorescent protein (EGFP) gene

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    Lee, Yong Jin; Lee, You La; Ahn, Sohn Joo; Choi, Chang Ik; Lee, Sang Woo; Ahn, Byeong Cheol; Lee, Jae Tae [School of Medicine, Kyungpook National University, Daegu (Korea, Republic of)


    To develop a non-invasive combined imaging method of gamma camera and optical imaging to assess rat myoblast cell line, H9c2, we constructed retrovirus containing hNIS and EGFP gene, and transfected to rat myoblast cell and monitored hNIS and EGFP expression. Rat myoblast cell line, H9C2, was transfected with hNIS and EGFP gene using retrovirus (H9C2-NG). The expression of hNIS and EGFP gene was determined by RT-PCR and fluorescence microscopy, respectively. The uptake and efflux of I-125 were measured in the transfected and wild type cell lines. Each cell line was injected to 4 flank sites (H9c2: 1X107 or 2X107, H9C2-NG: 1X107 or 2X107) in nude mouse. Scintigraphic image was performed at 3h, 1 day after H9C2 and H9C2-NG cell inoculation. We performed gamma camera and animal PET imaging to evaluate NIS expression. Also, GFP image obtained using optical imaging system. The expression of hNIS and EGFP gene was confirmed by RT-PCR. In iodide uptake, H9C2-NG cells accumulated 274.52.2 pmol/ mg protein at 30 min. But wild type cell line did not uptake iodide. In fluorescent microscopy, H9C2-NG cells were highly fluorescent than that of H9C2 cells. In iodide efflux study, 50% of radioactivity flowed out during the first 10min. Scintigraphy showed increased uptake of Tc-99m in H9c2-NG than in H9C2 for 1 day. Also, H9C2-NG cells showed high signal-to-background fluorescent spots in animal body. In this study, NIS and EGFP reporter gene were successfully transfected by a retrovirus in myoblast cell line, and the transfected cell can be easily visualized in vivo. These results suggest that NIS and EGFP gene has an excellent feasibility as a reporter gene, and it can be used to monitor cell trafficking for monitoring.

  2. The effect of tanespimycin (17-AAG) on radioiodine accumulation in sodium iodide symporter expressing cells

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    Yu, Kyoung Hyun; Youn, Hyewon; Song, Myung Geun; Lee, Dong Soo; Chung, June Key [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)


    The heat shock protein 90 inhibitor, tanespimycin, is an anticancer agent known to increase iodine accumulation in normal and cancerous thyroid cells. Iodine accumulation is regulated by membrane proteins such as sodium iodide sym porter (NIS) and pendrin (PDS), and thus we attempted to characterize the effects of tanespimycin on those genes. Cells were incubated with tanespimycin in order to evaluate {sup 125}I accumulation and efflux ability. Radioiodine uptake and efflux were measured by a gamma counter and normalized by protein amount. RT PCR were performed to measure the level of gene expression. After tanespimycin treatment, {sup 125}uptake was in creased by {approx}2.5 fold in FRTL 5, hNIS ARO. and hNIS MDA MB 231 cells, but no changes were detected in the hNIS HeLa cells. Tanespimycin significantly reduced the radioiodine efflux rate only in the FRTL 5 cell. in the FRTL 5 and hNIS ARO cells, PDS mRNA levels were markedly reduced; the only other observed alteration in the levels of NIS mRNA after tanespimtycin treatment was an observed increase in the h hNIS ARO cells. These results indicate that cellular responses against tanespimycin treatment differed between the normal rat thyroid cells and human cancer cells, and the reduction in the {sup 125I} efflux rate by tanespimycin in the normal rat thyroid cells might be attributable to reduced PDS gene expression.

  3. Radioiodinated Capsids Facilitate In Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors. (United States)

    Kothari, P; De, B P; He, B; Chen, A; Chiuchiolo, M J; Kim, D; Nikolopoulou, A; Amor-Coarasa, A; Dyke, J P; Voss, H U; Kaminsky, S M; Foley, C P; Vallabhajosula, S; Hu, B; DiMagno, S G; Sondhi, D; Crystal, R G; Babich, J W; Ballon, D


    Viral vector mediated gene therapy has become commonplace in clinical trials for a wide range of inherited disorders. Successful gene transfer depends on a number of factors, of which tissue tropism is among the most important. To date, definitive mapping of the spatial and temporal distribution of viral vectors in vivo has generally required postmortem examination of tissue. Here we present two methods for radiolabeling adeno-associated virus (AAV), one of the most commonly used viral vectors for gene therapy trials, and demonstrate their potential usefulness in the development of surrogate markers for vector delivery during the first week after administration. Specifically, we labeled adeno-associated virus serotype 10 expressing the coding sequences for the CLN2 gene implicated in late infantile neuronal ceroid lipofuscinosis with iodine-124. Using direct (Iodogen) and indirect (modified Bolton-Hunter) methods, we observed the vector in the murine brain for up to one week using positron emission tomography. Capsid radioiodination of viral vectors enables non-invasive, whole body, in vivo evaluation of spatial and temporal vector distribution that should inform methods for efficacious gene therapy over a broad range of applications.

  4. Sodium-iodine symporter gene expression controlled by the EGR-1 promoter: biodistribution, imaging and in vitro radionuclide therapy with Na(131)I. (United States)

    Tang, Jun; Wang, Xiaoxia; Xu, Yuanqi; Shi, Yizhen; Liu, Zengli; Yang, Yi


    The objective of this study is to explore the feasibility of radioiodine treatment for cervical cancer using the early growth response (Egr-1) promoter to control sodium-iodine symporter (hNIS) gene expression. The hNIS gene was previously transfected into Hela cells under the control of either the cytomegalovirus (CMV) or Egr-1 promoters. Na(125)I uptake was measured in the presence or absence of NaClO4. Na(125)I efflux was measured. The effects of external beam radiation on iodine uptake and retention were studied. The cytotoxic effects of (131)I were measured by clonogenic assay. The Na(125)I biodistribution was obtained using mice bearing control and transfected cells. The %ID/g of tumor and major organs were obtained for a range of times up to 48 hours post injection and the ratio of tumor to non-tumor activity (T/NT) was calculated. Tumors were imaged with Na(131)I and (99m)TcO4 (-), and the ratio of tumor to background activity (T/B) was calculated. Na(125)I uptake in Hela cells was minimal in the absence of hNIS. Uptake in the transfected cells was strong, and could be blocked by NaClO4. The iodine uptake of Hela-Egr-1-hNIS cells increased after the irradiation, and the magnitude of this effect approximately matched the radiation dose delivered. The efflux of 125I was affected by neither the promoter sequence nor pre-irradiation. (131)I reduced the clonogenic survival of symporter expressing cells, relative to the parental line. The effect was greatest in cells where hNIS was driven by the CMV promoter. Tumors formed from Hela-Egr-1-hNIS concentrated Na(125)I over a 12 hour period, in contrast to untransfected cells. These tumors could also be successfully imaged using either Na(131)I or (99m)TcO4 (-). (131)I uptake peaked at 4h, while (99m)TcO4 (-) accumulated over approximately 20 hours. In vivo uptake of (131)I and (99m)TcO4 (-) was slightly higher in cells transfected with the Egr-1 promoter, compared to CMV. Hela-Egr-1-hNIS cells demonstrate highly

  5. In vivo image of radioiodinated IVDU and IVFRU in HSV-TK gene tranduced hepatocellular carcinoma bearing buffalo rat

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    Lee, Tae Sup; Choi, T. H.; Ahn, S. H.; Woo, K. S.; Chung, W. S.; Lee, S. J.; Choi, C. W. [Korea Cancer Center Hospital, Seoul (Korea, Republic of)


    The extent of gene delivery and expression in gene therapy with suicide genes such as herpes simplex virus thymidine kinase (HSV-tk) is assessed with measurement of selective localization of radioiodinated HSV-tk substrates in HSV-tk expressing tumor. We compared n vitro uptake of {sup 125}I-IVDU, IVFRU and in vivo image of HSV-tk gene tranduced hepatocellular carcinoma model. Using H{sub 2}O{sub 2}(hydrogen peroxide), IVDU and IVFRU was radiolabeled as carrier free form. The uptake of {sup 125}I-IVDU IVFRU was determined with increasing incubation periods in MCA-tk and MCA cell line (1X10{sup 6}cell/flask). The cell harvested and counted after incubation of 15, 30, 60, 120, 240, 480 minutes. For estimating accumulation of radiolabelled IVDU, IVFRU in HSV-tk expressing tumor, MCA-tk cells (1 X 10{sup 6}/100 {mu}l) injected intramuscularly into right thigh of buffalo rats. To determine selective localization of radiolabelled IVDU, IVFRU in HSV-tk expressing hepatocellular carcinoma bearing buffalo rats, MCA-tk cells (1X 10{sup 7} cell/100 {mu}l) were injected subcutaneously into both shoulders of buffalo rats. Established tumor mass implanted into liver of buffalo rats using intra-hepatic tumor injection. Two weeks later, {sup 123}I labelled IVDU, IVFRU(7.4 X 10{sup 7}Bq/200 {mu}l) injected intravenously into tail veins of each buffalo rats. Gamma camera used as revealing localization of {sup 123}I-IVDU, IVFRU in MCA-tk cells grafts rats and in vivo image was taken 2 hrs, 24 hrs after injection. radioiodinated IVDU, IVFRU were radiolabeled with {sup 123}I as labeling yield 70%, {sup 125}I as 84%. Two compounds showed minimal uptake in MCA cell line, but in MCA-tk cell line, increased uptake was observed. The ratio of MCA-tk to MCA was up to 116-fold in {sup 125}I-IVDU, up to 37-fold in {sup 125}I-IVFRU at 480 min. The uptake of IVDU was 4 times higher than IVFRU in MCA-tk cells. Gamma camera images of HSV-tk gene tranduced MCA tumor showed accumulation of {sup 123}I

  6. Expression of the human sodium/iodide symporter (hNIS) in xenotransplanted human thyroid carcinoma

    NARCIS (Netherlands)

    Smit, J.W.A.; Schröder - van der Elst, J.P.; Karperien, M.; Que, I.; Romijn, J.A.; Heide, van der D.


    The uptake of iodide in thyroid epithelial cells is mediated by the sodium/iodide symporter (NIS). The uptake of iodide is of vital importance for thyroid physiology and is a prerequisite for radioiodine therapy in thyroid cancer. Loss of iodide uptake due to diminished expression of the human NIS

  7. Radioiodine and pregnancy. (United States)

    Gorman, C A


    The fetal thyroid begins to accumulate radioiodine around the 12th week of pregnancy. Iodide easily crosses the placenta and fetal thyroid uptake can be effectively blocked by administration of radioiodine to the mother. Therapeutic administration of radioiodine to the mother will usually result in fetal hypothyroidism and may be associated with attention deficit disorders and impairment of figurative memory in the offspring. The hazard to a fetus from exposure to a family member, not the mother, who has been treated with radioiodine is very small and can be minimized by adherence to standard post treatment guidelines. Lactating mothers who have received standard diagnostic doses of 131I or who have been treated with 131I should not breast-feed their infant from that point forward. Breast-feeding in future pregnancies is not contraindicated. Pregnancy testing within 48 hours before 131I administration to potentially fertile women is a wise clinical practice. Demonstrated effects of radioiodine on spermatogenesis suggest that it is wise to recommend a 120-day waiting period between radioiodine and fertilization.

  8. Mesenchymal stem cell-mediated, tumor stroma-targeted radioiodine therapy of metastatic colon cancer using the sodium iodide symporter as theranostic gene. (United States)

    Knoop, Kerstin; Schwenk, Nathalie; Schmohl, Kathrin; Müller, Andrea; Zach, Christian; Cyran, Clemens; Carlsen, Janette; Böning, Guido; Bartenstein, Peter; Göke, Burkhard; Wagner, Ernst; Nelson, Peter J; Spitzweg, Christine


    The tumor-homing property of mesenchymal stem cells (MSCs) allows targeted delivery of therapeutic genes into the tumor microenvironment. The application of sodium iodide symporter (NIS) as a theranostic gene allows noninvasive imaging of MSC biodistribution and transgene expression before therapeutic radioiodine application. We have previously shown that linking therapeutic transgene expression to induction of the chemokine CCL5/RANTES allows a more focused expression within primary tumors, as the adoptively transferred MSC develop carcinoma-associated fibroblast-like characteristics. Although RANTES/CCL5-NIS targeting has shown efficacy in the treatment of primary tumors, it was not clear if it would also be effective in controlling the growth of metastatic disease. To expand the potential range of tumor targets, we investigated the biodistribution and tumor recruitment of MSCs transfected with NIS under control of the RANTES/CCL5 promoter (RANTES-NIS-MSC) in a colon cancer liver metastasis mouse model established by intrasplenic injection of the human colon cancer cell line LS174t. RANTES-NIS-MSCs were injected intravenously, followed by (123)I scintigraphy, (124)I PET imaging, and (131)I therapy. Results show robust MSC recruitment with RANTES/CCL5-promoter activation within the stroma of liver metastases as evidenced by tumor-selective iodide accumulation, immunohistochemistry, and real-time polymerase chain reaction. Therapeutic application of (131)I in RANTES-NIS-MSC-treated mice resulted in a significant delay in tumor growth and improved overall survival. This novel gene therapy approach opens the prospect of NIS-mediated radionuclide therapy of metastatic cancer after MSC-mediated gene delivery. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  9. (Radioiodinated free fatty acids)

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    Knapp, Jr., F. F.


    The traveler participated in the Second International Workshop on Radioiodinated Free Fatty Acids in Amsterdam, The Netherlands where he presented an invited paper describing the pioneering work at the Oak Ridge National Laboratory (ORNL) involving the design, development and testing of new radioiodinated methyl-branched fatty acids for evaluation of heart disease. He also chaired a technical session on the testing of new agents in various in vitro and in vivo systems. He also visited the Institute for Clinical and Experimental Nuclear Medicine in Bonn, West Germany, to review, discuss, plan and coordinate collaborative investigations with that institution. In addition, he visited the Cyclotron Research Center in Liege, Belgium, to discuss continuing collaborative studies with the Osmium-191/Iridium-191m radionuclide generator system, and to complete manuscripts and plan future studies.

  10. Radioiodine and thyroid gland

    Directory of Open Access Journals (Sweden)

    Takavar A


    Full Text Available Administration of a precise amount of activity in thyroid gland radioiodine (¹³¹I therapy is of prime importance. Several methods for this purpose have been suggested and used over many years. In this paper, a method for required ¹³¹I activity calculation for each case has been proposed. Major factors affecting ¹³¹I calculation such as gland volume, integral dose, and prescription index have been described. Using the method, ¹³¹I activity or any other radioisotope activity required for a certain case can be determined with a good estimate.

  11. Dual-expressing adenoviral vectors encoding the sodium iodide symporter for use in noninvasive radiological imaging of therapeutic gene transfer

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    Niu Gang [Free Radical and Radiation Biology Program, The University of Iowa, Iowa City, IA 52242 (United States); Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242 (United States); Anderson, Richard D. [ViraQuest Inc., North Liberty, IA 52317 (United States); Madsen, Mark T. [Department of Radiology, University of Iowa, Iowa City, IA 52242 (United States); Carver College of Medicine and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242 (United States); Graham, Michael M. [Department of Radiology, University of Iowa, Iowa City, IA 52242 (United States); Carver College of Medicine and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242 (United States); Oberley, Larry W. [Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA 52242 (United States); Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242 (United States); Carver College of Medicine and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242 (United States); Domann, Frederick E. [Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA 52242 (United States) and Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242 (United States) and Carver College of Medicine and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242 (United States)]. E-mail:


    Introduction: Noninvasive analysis of therapeutic transgene expression is important for the development of clinical translational gene therapy strategies against cancer. To image p53 and MnSOD gene transfer noninvasively, we used radiologically detectable dual-expressing adenoviral vectors with the human sodium iodide symporter (hNIS) as the reporter gene. Methods: Dual-expressing adenoviral vectors were constructed with hNIS cloned into E3 region and therapeutic genes, either MnSOD or p53, recombined into the E1 region. Steady-state mRNA levels of hNIS were evaluated by real-time polymerase chain reaction. hNIS function was determined by iodide uptake assay and MnSOD, and p53 protein levels were assessed by Western blots. Results: {sup 125}I{sup -} accumulation resulting from hNIS expression in both Ad-p53-hNIS- and Ad-MnSOD-hNIS-infected MDA-MB-435 cells could be visualized clearly on phosphorimaging autoradiograph. Iodide accumulation increased with increasing adenovirus titer, and there was a linear correlation between iodide uptake and dose. p53 and MnSOD protein levels increased as a function of adenovirus titer, and there was a direct positive correlation between p53 and MnSOD expression and hNIS function. P53 and MnSOD overexpression inhibited cell growth in the dual-expressing adenoviral vector-infected cells. Conclusions: Radiological detection of hNIS derived from dual-expressing adenoviral vectors is a highly effective method to monitor therapeutic gene transfer and expression in a noninvasive manner.

  12. EGFR-Targeted Adenovirus Dendrimer Coating for Improved Systemic Delivery of the Theranostic NIS Gene

    Directory of Open Access Journals (Sweden)

    Geoffrey K Grünwald


    Full Text Available We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of combined radiovirotherapy after systemic delivery of the theranostic sodium iodide symporter (NIS gene using a dendrimer-coated adenovirus. To further improve shielding and targeting we physically coated replication-selective adenoviruses carrying the hNIS gene with a conjugate consisting of cationic poly(amidoamine (PAMAM dendrimer linked to the peptidic, epidermal growth factor receptor (EGFR-specific ligand GE11. In vitro experiments demonstrated coxsackie-adenovirus receptor-independent but EGFR-specific transduction efficiency. Systemic injection of the uncoated adenovirus in a liver cancer xenograft mouse model led to high levels of NIS expression in the liver due to hepatic sequestration, which were significantly reduced after coating as demonstrated by 123I-scintigraphy. Reduction of adenovirus liver pooling resulted in decreased hepatotoxicity and increased transduction efficiency in peripheral xenograft tumors. 124I-PET-imaging confirmed EGFR-specificity by significantly lower tumoral radioiodine accumulation after pretreatment with the EGFR-specific antibody cetuximab. A significantly enhanced oncolytic effect was observed following systemic application of dendrimer-coated adenovirus that was further increased by additional treatment with a therapeutic dose of 131I. These results demonstrate restricted virus tropism and tumor-selective retargeting after systemic application of coated, EGFR-targeted adenoviruses therefore representing a promising strategy for improved systemic adenoviral NIS gene therapy.

  13. EGFR-Targeted Adenovirus Dendrimer Coating for Improved Systemic Delivery of the Theranostic NIS Gene. (United States)

    Grünwald, Geoffrey K; Vetter, Alexandra; Klutz, Kathrin; Willhauck, Michael J; Schwenk, Nathalie; Senekowitsch-Schmidtke, Reingard; Schwaiger, Markus; Zach, Christian; Wagner, Ernst; Göke, Burkhard; Holm, Per S; Ogris, Manfred; Spitzweg, Christine


    We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of combined radiovirotherapy after systemic delivery of the theranostic sodium iodide symporter (NIS) gene using a dendrimer-coated adenovirus. To further improve shielding and targeting we physically coated replication-selective adenoviruses carrying the hNIS gene with a conjugate consisting of cationic poly(amidoamine) (PAMAM) dendrimer linked to the peptidic, epidermal growth factor receptor (EGFR)-specific ligand GE11. In vitro experiments demonstrated coxsackie-adenovirus receptor-independent but EGFR-specific transduction efficiency. Systemic injection of the uncoated adenovirus in a liver cancer xenograft mouse model led to high levels of NIS expression in the liver due to hepatic sequestration, which were significantly reduced after coating as demonstrated by (123)I-scintigraphy. Reduction of adenovirus liver pooling resulted in decreased hepatotoxicity and increased transduction efficiency in peripheral xenograft tumors. (124)I-PET-imaging confirmed EGFR-specificity by significantly lower tumoral radioiodine accumulation after pretreatment with the EGFR-specific antibody cetuximab. A significantly enhanced oncolytic effect was observed following systemic application of dendrimer-coated adenovirus that was further increased by additional treatment with a therapeutic dose of (131)I. These results demonstrate restricted virus tropism and tumor-selective retargeting after systemic application of coated, EGFR-targeted adenoviruses therefore representing a promising strategy for improved systemic adenoviral NIS gene therapy.Molecular Therapy-Nucleic Acids (2013) 2, e131; doi:10.1038/mtna.2013.58; published online 5 November 2013.

  14. Radioiodine therapy of thyroid autonomy

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    Reiners, Christoph; Schneider, Peter [Clinic and Policlinic for Nuclear Medicine, University of Wuerzburg, Josef-Schneider-Strasse 2, 97080 Wuerzburg (Germany)


    Over half a century, treatment of thyroid autonomy with an oral dose of iodine-131 has proven to be effective. The optimum management strategy for the patient is, however, still a matter of debate. The article provides an overview of the pathogenesis of functional autonomy and its clinical relevance. According to the guidelines on both sides of the Atlantic, radioiodine treatment is considered the most comfortable and economical approach to the treatment of the toxic nodular goitre. Some differences in the preparation procedures in the guidelines of the American and the German Society of Nuclear Medicine are discussed with respect to therapy results and the subtypes of thyroid autonomy. The results of studies are summarised concerning changes in thyroid function and thyroid volume after a course of radioiodine treatment. Therapy-related risks, such as immunogenic hypothyroidism or thyroid cancer, are discussed. {sup 131}I treatment of functional autonomy and hyperthyroidism is considered an effective and safe procedure. (orig.)

  15. Study of potential inhibitors of thyroid iodide uptake by using CHO cells stably expressing the human sodium/iodide symporter (hNIS) protein. (United States)

    Agretti, P; Dimida, A; De Marco, G; Ferrarini, E; Rodrìguez Gonzàlez, J C; Santini, F; Vitti, P; Pinchera, A; Tonacchera, M


    Thyroid gland is highly dependent on dietary intake of iodine for normal function, so it is particularly subjected to "endocrine disruptor" action. The human sodium/iodide symporter (hNIS) is an integral plasma membrane glycoprotein mediating the active transport of iodide into thyroid follicular cells, a crucial step for thyroid hormone biosynthesis. Beyond to perchlorate and thyocianate ions a few other inhibitors of iodide uptake have been described. The aim of this study was to investigate if 10 substances usually used as drugs in clinical practice were able to inhibit NIS-mediated iodide uptake in vitro. A CHO cell line stably expressing hNIS was used to test any inhibition of NIS-mediated iodide uptake exerted by drugs. Perchlorate and thyocianate ions were used as positive controls. None of the analyzed substances was able to significantly inhibit iodide uptake in our system. As we expected, perchlorate and thyocianate ions were able to inhibit iodide uptake in a dose-dependent manner. In conclusion, we carried out an in vitro assay to evaluate the potential inhibitory effect of common drugs on NISmediated iodide uptake by using CHO-hNIS cells. None of the analyzed substances was able to inhibit iodide uptake; only perchlorate and thyocianate were able to inhibit iodide uptake in a dose-dependent manner.

  16. Radioiodine uptake in inactive pulmonary tuberculosis

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    Bakheet, S.M.; Powe, J.; Al Suhaibani, H. [Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia); Hammami, M.M.; Bazarbashi, M. [Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)


    Radioiodine may accumulate at sites of inflammation or infection. We have seen such accumulation in six thyroid cancer patients with a history of previously treated pulmonary tuberculosis. We also review the causes of false-positive radioiodine uptake in lung infection/inflammation. Eight foci of radioiodine uptake were seen on six iodine-123 diagnostic scans. In three foci, the uptake was focal and indistinguishable from thyroid cancer pulmonary metastases from thyroid cancer. In the remaining foci, the uptake appeared nonsegmental, linear or lobar, suggesting a false-positive finding. The uptake was unchanged, variable in appearance or non-persistent on follow-up scans and less extensive than the fibrocystic changes seen on chest radiographs. In the two patients studied, thyroid hormone level did not affect the radioiodine lung uptake and there was congruent gallium-67 uptake. None of the patients had any evidence of thyroid cancer recurrence or of reactivation of tuberculosis and only two patients had chronic intermittent chest symptoms. Severe bronchiectasis, active tuberculosis, acute bronchitis, respiratory bronchiolitis, rheumatoid arthritis-associated lung disease and fungal infection such as Allescheria boydii and aspergillosis can lead to different patterns of radioiodine chest uptake mimicking pulmonary metastases. Pulmonary scarring secondary to tuberculosis may predispose to localized radioiodine accumulation even in the absence of clinically evident active infection. False-positive radioiodine uptake due to pulmonary infection/inflammation should be considered in thyroid cancer patients prior to the diagnosis of pulmonary metastases. (orig.) With 4 figs., 1 tab., 9 refs.

  17. Radioiodine in the Savannah River Site environment

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    Kantelo, M.V.; Bauer, L.R.; Marter, W.L.; Murphy, C.E. Jr.; Zeigler, C.C.


    Radioiodine, which is the collective term for all radioactive isotopes of the element iodine, is formed at the Savannah River Site (SRS) principally as a by-product of nuclear reactor operations. Part of the radioiodine is released to the environment during reactor and reprocessing operations at the site. The purpose of this report is to provide an introduction to radioiodine production and disposition, its status in the environment, and the radiation dose and health risks as a consequence of its release to the environment around the Savannah River Plant. A rigorous dose reconstruction study is to be completed by thee Center for Disease Control during the 1990s.

  18. Radioiodine treatment for non-toxic goitre

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla


    There is no ideal treatment for benign multinodular goitre. Besides surgery, which is recommended for large goitres or when malignancy cannot be excluded, the non-surgical treatment options are levothyroxine therapy and radioiodine ((131)I) therapy. Conventional (131)I therapy [without recombinant...... human thyroid-stimulating hormone (rhTSH)] has been used for more than a decade in symptomatic non-toxic multinodular goitre, and although it does lead to significant thyroid volume reduction, relatively high activities of radioiodine are needed because of a frequent finding of a low thyroid radioiodine...

  19. Immobilization of radioiodine in synthetic boracite (United States)

    Babad, H.; Strachan, D.M.


    A nuclear waste storage product is disclosed in which radioiodine is incorporated in a synthetic boracite. The boracite may be prepared by reacting a transition metal iodide with an alkali horate under mild hydrothermal conditions, drying the reaction product, and then hot pressing.

  20. [Lenvatinib in radioiodine refractory thyroid carcinomas]. (United States)

    de la Fouchardiere, Christelle


    Differentiated thyroid cancers are usually cured by an appropriate surgery and a radioiodine remnant ablation. If metastases occur, successive radioiodine administrations and/or local treatments can be provided. Nevertheless, some patients will be, or become refractory to radioiodine. In case of significant and rapid progression of metastatic lesions, they will be candidate to kinase inhibitor treatments. Two agents are now approved in this situation: sorafenib and lenvatinib. Lenvatinib (Lenvima®) is a tyrosine kinase inhibitor (TKI) targeting the VEGFR1-3, FGFR 1-4, PDGFR-α, RET and c-kit. It received an FDA and EMA approval in February and March 2015 for the treatment of radioiodine refractory thyroid cancers following the SELECT study's results. In this study, patients treated with lenvatinib had a significant increase in progression-free survival (18.3 months vs. 3.6 months; HR=0.21; CI=0.14-0.31, P Cancer. Published by Elsevier Masson SAS. All rights reserved.

  1. Radioiodine treatment for malignant thyroid disease

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    Berg, Gertrud [Sahlgrenska Univ. Hospital, Goeteborg (Sweden). Dept. of Oncology


    Radioiodine treatment for thyroid disease has been given for half a decade in Sweden. The most common indication for treatment is hyperthyroidism, when iodine uptake is high. The situation in which radioiodine treatment is used in thyroid cancer is less favourable and measures therefore have to be taken to optimize the treatment. Treatment should be performed early in the course of the disease to achieve the highest possible differentiation. Before treatment the iodine and goitrogen intake should be kept low. Stimulation of the thyrocytes by thyroid-stimulating hormone (TSH) should be high. It is conventionally achieved by thyroid hormone withdrawal rendering the patient hypothyroid, or by the recently available recombinant human TSH (rhTSH) which can be recommended for ablation of the thyroid remnant after thyroidectomy and for treatment of metastases in fragile patients unable to undergo hypothyroidism. Finally, stunning - the negative effect of a prior test dose from radioactive iodine - should be avoided.

  2. An improved method for hyaluronic acid radioiodination

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    Orlando, P.; De Feo, A.; Orlando, M.; Trenta, R.; Trevisi, R. [Universita Cattolica del Sacro Cuore, Rome (Italy). Centro Radioisotopi; Binaglia, L. [Perugia Univ. (Italy). Ist. di Biochimica e Chimica Medica


    A simple procedure is described for preparing {sup 125}I-labelling hyluronan of high molecular weight. The reducing terminal group of hyaluronic acid was derivatized with tyramine through the formation of a Schiff base which was subsequently reduced with sodium cyanoborohydride. By radioiodination of the aromatic ring, {sup 125}I-labelled hyaluronic acid was obtained in high yield (40%) and high specific activity, 555 GBq/mmol (15 Ci/mmol). (Author).

  3. Radioiodine therapy in hyperthyroid disease: poorer outcome in patients with high 24 hours radioiodine uptake

    DEFF Research Database (Denmark)

    Kristoffersen, Ulrik Sloth; Hesse, Birger; Rasmussen, Ase Krogh


    PURPOSE: To evaluate the importance of 24 h radioiodine uptake (24 h RIU) for the outcome of radioiodine treatment of hyperthyroidism. METHODS: Retrospective analysis of 72 patients who underwent radioiodine treatment for toxic goiter at our outpatient clinic [29 diffuse goiters (DG), 30 toxic...... multinodular goiters (TMG) and 13 toxic adenomas (TA)]. Thyroid status was determined by TSH, fT3 and fT4 levels, and outcome was rendered successful when hyperthyroidism was absent. Relation between low 24 h RIU (below median) or high 24 h RIU (above or equal to median) and outcome was evaluated. RESULTS......: Of patients with DG and low 24 h RIU, 15% remained hyperthyroid, as opposed to 56% of patients with DG and high 24 h RIU (Phyperthyroid, as opposed to 44% of patients with TMG and high 24 h RIU (P

  4. Total Thyroidectomy in the Mouse: the Feasibility Study in the Non thyroidal Tumor Model Expressing Human Sodium/Iodide Symporter Gene

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Hye kyung; Kim, Seog Gyun; Kim, Tae Sung; Kim, Seok ki; Lee, Sang Jin [Hospital and Research Institute, National Cancer Center, Goyang (Korea, Republic of)


    This study sought to probe the feasibility of performing total thyroidectomy in the mouse using a non thyroidal hNIS expressing tumor model. Our thyroidectomy protocol included thorough excision of both lobes and the isthmus. For evaluating the completeness of thyroidectomy, we compared the {sup 99m}Tc pertechnetate scans taken before and after thyroidectomy. The prostate scans taken before and after thyroidectomy. The prostate cancer cell line was subcutaneously inoculated 2 weeks after the thyroidectomy. When the tumor reached 5-10mm in diameter, Ad5/35 E4PSESE1a hNIS was injected intratumorally, and {sup 131I} scans were performed. The radio iodine uptakes of the neck and the tumor were compared with those of the other regions. Total thyroidectomy was performed in 13 mice. Although 38.5% died during or just after thyroidectomy, the others survived in good health for 2 months. Thyroid tissue was completely eliminated using our protocol; the residual uptake of {sup 99m}Tc pertechnetate was minimal in the neck area. The neck/background uptake ratio after thyroidectomy (p<0.05). Non thyroidal tumor models were successfully established in all the surviving mice. Radioiodine accumulation in the tumors was visualized on {sup 131I} scans, and the neck uptakes were minimal. Using our total thyroidectomy protocol, we successfully established a hNIS transfected prostate cancer model with a minimal accumulation of radioiodine in the neck. The relatively high mortality after surgery can be a problem, and this might be reduced by minimizing the surgical stress.

  5. Microbial copper reduction method to scavenge anthropogenic radioiodine (United States)

    Lee, Seung Yeop; Lee, Ji Young; Min, Je Ho; Kim, Seung Soo; Baik, Min Hoon; Chung, Sang Yong; Lee, Minhee; Lee, Yongjae


    Unexpected reactor accidents and radioisotope production and consumption have led to a continuous increase in the global-scale contamination of radionuclides. In particular, anthropogenic radioiodine has become critical due to its highly volatile mobilization and recycling in global environments, resulting in widespread, negative impact on nature. We report a novel biostimulant method to effectively scavenge radioiodine that exhibits remarkable selectivity for the highly difficult-to-capture radioiodine of >500-fold over other anions, even under circumneutral pH. We discovered a useful mechanism by which microbially reducible copper (i.e., Cu2+ to Cu+) acts as a strong binder for iodide-iodide anions to form a crystalline halide salt of CuI that is highly insoluble in wastewater. The biocatalytic crystallization of radioiodine is a promising way to remove radioiodine in a great capacity with robust growth momentum, further ensuring its long-term stability through nuclear I- fixation via microcrystal formation.

  6. Development of dual reporter system of mutant dopamine 2 receptor (D{sub 2}R) and sodium iodide symporter (NIS) transgenes

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Do Won; Lee, Dong Soo; Kang, Joo Hyun; Chang, Young Soo; Kim, Yun Hui; Jeong, Jae Min; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)


    Both human NIS and mutant D{sub 2}R 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{sub 2}R) and compared its characteristics. The recombinant plasmid (pIRES-hNIS/D{sub 2}R) was constructed with IRES (internal ribosome entry site) under control of the CMV promoter. pIRES-hNIS/D{sub 2}R was transfected to human hepatoma SK-Hep1 cell line with lipofectamine. HEP-ND(SK-Hep1-hNIS/D{sub 2}R) cells stably expressing hNIS and D{sub 2}R was established by selection with G418 for two weeks. RT-PCR was performed to investigate the expression of both hNIS and D{sub 2}R genes. The expressions of hNIS and D{sub 2}R were measured by {sup 125}I uptake assays and receptor binding assays. Specific binding of D{sub 2}R to [{sup 3}H]spiperone was verified by Scatchard plot with (+) butaclamol as a specific inhibitor. K{sub d} and B{sub max} values were estimated. The correlation between hNIS and D{sub 2}R expression was compared by using each clone. Similar quantities of hNIS and D{sub 2}R 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. {sup 125}I uptake in HEP-ND cells was completely inhibited by KCIO{sub 4}, a NIS inhibitor. Specific binding to HEP-ND cells was saturable and the K{sub d} and B{sub max} values for HEP-ND cells were 2.92 nM, 745.25 fmol/mg protein and 2.91 nM, 1323 fmole/mg protein in two clones, respectively. The radioiodine uptake by hNIS activity and D{sub 2}R binding was highly correlated. We developed a dual positron and gamma imaging reporter system of hNIS and D{sub 2}R in a stably transfected cell line. We expect that D{sub 2}R and hNIS genes can complement mutually as a nuclear reporting system or that D{sub 2}R cna be used as reporter gene when hNIS gene were used as a treatment gene.

  7. Radioiodine therapy in benign thyroid diseases

    DEFF Research Database (Denmark)

    Bonnema, Steen Joop; Hegedüs, Laszlo


    Radioiodine ((131)I) therapy of benign thyroid diseases was introduced 70 yr ago, and the patients treated since then are probably numbered in the millions. Fifty to 90% of hyperthyroid patients are cured within 1 yr after (131)I therapy. With longer follow-up, permanent hypothyroidism seems...... of an exact thyroid dose is error-prone due to imprecise measurement of the (131)I biokinetics, and the importance of internal dosimetric factors, such as the thyroid follicle size, is probably underestimated. Besides these obstacles, several potential confounders interfere with the efficacy of (131)I therapy...... from (131)I therapy. The individual radiosensitivity, still poorly defined and impossible to quantify, may be a major determinant of the outcome from (131)I therapy. Above all, the impact of (131)I therapy relies on the iodine-concentrating ability of the thyroid gland. The thyroid (131)I uptake (or...

  8. Radioiodine in kelp from western Australia

    Energy Technology Data Exchange (ETDEWEB)

    Marsh, K.V.; Buddemeier, R.W.; Wood, W.; Smith, C.


    As part of a program to survey low levels of radioactivity in the marine environment of the southern hemisphere, we have studied the distribution and uptake of /sup 131/I found in the subtidal kelp Ecklonia radiata, on the west coast of Australia. Concentrations of 5 to 75 fCi/g of /sup 131/I exist in this species over a considerable distance along the coast. We have characterized the principal source of the /sup 131/I and found a general temporal correlation between the amount of radioiodine discharged from sewer outfalls and its concentration in kelp. Transplant experiments have enabled us to estimate uptake and depuration rates, and our results are consistent with laboratory measurements made by others.

  9. Metal organic framework MIL-101 for radioiodine capture and storage (United States)

    Assaad, Thaer; Assfour, Bassem


    we report on the use of metal organic frameworks(MOFs) for radioiodine recovery and storage. One MOF (namely MIL-101) was prepared and investigated in detail to demonstrate the iodine removal efficiency and capacity of MOFs. The typical sorption kinetics and uptake isotherms were measured using radioactive iodine (123 I) for the first time. Our measurements indicate that MOFs can capture and store radioiodine in very high efficiency and fast kinetics.

  10. Biochemistry of radioiodinated free fatty acids. (United States)

    Visser, F C; Duwel, C M; van Eenige, M J; Roos, J P; Knapp, F F; van der Vusse, G J

    Radioiodinated free fatty acids have been developed to study myocardial metabolism non-invasively in man. In the present study the distribution of radiolabeled lipids in the myocardium and in arterial and coronary sinus blood was evaluated following injection of three commonly used iodinated fatty acids in fasted (n = 5) and lactate loaded (n = 3) dogs. Five minutes after simultaneous i.v. injection of radioiodinated 17-I-heptadecanoic acid (IHDA), 15-(p-I-phenyl) pentadecanoic acid (IPPA) and 15-(p-I-phenyl)-3,3-dimethyl-pentadecanoic acid (DMIPPA) a biopsy specimen and samples of arterial and coronary sinus blood were taken. After extraction and TLC the relative distribution of radioactivity in the aqueous phase (containing the oxidation products), pellet and organic phase was calculated. The organic phase was further divided into phospholipids, diglycerides, free fatty acids, triglycerides and cholesterol-esters. Seventy two percent of IHDA was oxidized, 36% of IPPA and 7% of DMIPPA. The organic phase consisted primarily of triglycerides and phospholipids. The ratios of triglycerides to phospholipids were about the same for IHDA, IPPA and DMIPPA (0.58, 0.65 and 0.50, respectively). Free IHDA in tissue samples was low (4%) and elevated for IPPA and DMIPPA, (17% and 37%). During lactate loading triglycerides were higher for all three fatty acids. For IHDA and IPPA this increase was paralleled by a decrease in the aqueous phase, in case of DMIPPA the aqueous phase remained the same. Five minutes after injection most of the organic phase of both arterial and coronary sinus blood consisted of the injected fatty acids, the aqueous phase contained oxidation products. There were only minor differences during lactate loading.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Patterns of radioiodine uptake by the lactating breast

    Energy Technology Data Exchange (ETDEWEB)

    Bakheet, S.M. (Dept. of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)); Hammami, M.M. (Dept. of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia))


    Breast uptake of radioiodine, if not suspected, may be misinterpreted as thyroid cancer metastasis to the lung. To characterize the patterns of radioiodine breast uptake, we retrospectively studied 20 radioiodine scans that were performed within 1 week of cessation of breast feeding. Four patterns of uptake were identified: ''full'', ''focal'', ''crescent'' and ''irregular''. The uptake was asymmetric in 60% (left>right in 45%, right>left in 15%), symmetric in 25% and unilateral in 15% of cases. A characteristic full bilateral uptake was present in 40% of cases. In three cases with the irregular pattern, caused in part by external contamination with radioactive milk, the uptake closely mimicked lung metastases. Delayed images, obtained in one case, showed an apparent radioiodine shift from the breast to the thyroid, suggesting that the presence of breast uptake can modulate radioiodine uptake by thyroid tissue. In a case of unilateral breast uptake, a history of mastitis was obtained, which to our knowledge has not been previously reported. Breast uptake of radioiodine may take several scintigraphic patterns that are not always characteristic of the lactating breast and may affect the apparent extent of thyroid remnant/metastasis. (orig.)

  12. {sup 99m}Tc-pertechnetate uptake in hepatoma cells due to tissue-specific human sodium iodide symporter gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Chen Libo [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, 200233 Shanghai (China); Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ) and Heidelberg University, 69120 Heidelberg (Germany); Altman, Annette [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ) and Heidelberg University, 69120 Heidelberg (Germany); Mier, Walter [Department of Nuclear Medicine, University of Heidelberg, 69120 Heidelberg (Germany); Lu Hankui [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, 200233 Shanghai (China); Zhu Ruisen [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, 200233 Shanghai (China); Haberkorn, Uwe [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ) and Heidelberg University, 69120 Heidelberg (Germany) and Department of Nuclear Medicine, University of Heidelberg, 69120 Heidelberg (Germany)]. E-mail:


    The sodium iodide symporter (NIS) gene could be used as an ideal reporter gene as well as a promising therapeutic gene. {sup 99m}Tc-pertechnetate has proven to be more advantageous than {sup 131}I-iodide with respect to image quality, procedure and radiation dose in examination of thyroid uptake and scintigraphy. Herein, we investigated the feasibility of monitoring human sodium iodide symporter (hNIS) gene expression with {sup 99m}Tc-pertechnetate in hepatoma cells (MH3924A) following tissue-specific expression. Methods: MH3924A cells were stably transfected with the recombinant retroviral vector, in which hNIS cDNA was driven by murine albumin enhancer/promoter (mAlb) and coupled to hygromycin resistance gene using an internal ribosomal entry site. Functional NIS expression in hepatoma cells was confirmed by an {sup 125}I{sup -} uptake assay. The dynamic uptake and efflux of {sup 99m}Tc-pertechnetate was determined both in vitro and in vivo. Results: The {sup 99m}Tc-pertechnetate was up to 254-fold higher in stably transfected MH3924A cells than in wild-type cells. However, the in vitro efflux of {sup 99m}Tc-pertechnetate out of recombinant cells was rapid with a half-life of less than 2 min. Further, the in vivo studies yielded clear images and quantitative data of mAlbhNIS-infected tumor xenografts using {sup 99m}Tc-pertechnetate and {gamma} camera. Conclusion: The current study demonstrates enhanced {sup 99m}Tc-pertechnetate uptake in hepatoma cells in vitro and in vivo following tissue-specific gene transfer using a recombinant retrovirus with the albumin enhancer/promoter and the hNIS gene. It is feasible to monitor hNIS gene expression noninvasively and quantitatively using conventional {gamma} camera and {sup 99m}Tc-pertechnetate.

  13. Theophylline Increases the Uptake of Radioiodine by Mouse Thyroid (United States)

    Caturegli, Patrizio; Ladenson, Paul W.


    Diagnostic and therapeutic use of radioiodine in the management of thyroid disorders depends on the ability of thyroid cells to concentrate radioiodine, a process that is regulated by the intracellular increase in cAMP. We hypothesized that theophylline, a drug known to increase intracellular cAMP via inhibition of phosphodiesterase, could increase thyroidal radioiodine uptake. We tested this effect in vivo, using C57BL/6j mice, and in vitro, using Fisher rat thyroid (FRTL-5) cells. One mouse received 2.5mg theophylline i.p., whereas a control mouse received only saline. Twenty-hours after theophylline, mice were injected with 10 µCi Na125I in 0.1 mL saline through the tail vein. Mean thyroidal 125I activity was 3.3-fold higher in theophylline-treated mice than in their respective controls. Radioiodine uptake and intracellular cAMP production of FRTL-5 cells were increased by a relatively low concentration of theophylline (1 µM). Intracellular cAMP increased up to 30 min and then declined in response to 1 µM theophylline. Sera from theophylline-treated mice stimulated 125I uptake and intracellular cAMP production by FRTL-5 cells. These findings show that theophylline can enhance radioiodine uptake by thyrocytes in vivo and in vitro. The in vitro effects of theophylline on both radioiodine uptake and cAMP production in a dose-dependent manner are consistent with an action mediated by phosphodiesterase inhibition. PMID:15483348

  14. Radioiodinated fatty acid analogs for myocardial imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ruyan, M.K.


    Fatty acids are the preferred substrate for the normoxic heart. About sixty percent of the energy required by the myocardium is provided by fatty acid [beta]-oxidation. Many scientists have focused on the alterations in fatty acid metabolism in the ischemic heart for the development of radiolabelled fatty acids for functional imaging of the heart. Three main categories of compounds were synthesized: tetrazoles (1 and 2), glycidic and [alpha]-methylene acids (3-5), and analogs of oleic acid (6,7 and 7A). The tetrazole group has a similar pKa and size to that of a carboxyl group; however, such fatty acid analogs cannot undergo normal fatty acid metabolism. Glycidic and [alpha]-methylene analogs are potential irreversible inhibitors of fatty acid metabolism. Oleic acid analogs were investigated to assess the affect of stereochemical consequences on biodistribution. The key intermediates in the synthesis of the target compounds were [omega]-nitrophenyl alkylcarboxylic acids and alcohols, which were made using a variety of cross-coupling reactions. The Wittig reaction, which was used in the synthesis of tetrazole 1 and glycidic acid 3, gave low yields of the cross-coupled products. The remaining target compounds were synthesized by condensation of appropriate RCu (CN) ZnI and substituted benzyl bromides or by Pd[sup II] catalyzed cross-coupling of substituted arylhalides with suitable alkynes. The latter two reactions produced much higher yields of the desired products. All of the target compounds were radiolabeled with [sup 125]I by various Cu(I) catalyzed radioiodine exchange procedures and were then subjected to tissue biodistribution (TD) studies in rats. Except for the 15-(4-iodophenyl)-2-methylene-pentadecanoic acid (5), all of the fatty acid analogs failed to surpass clinically-used 15-(4-iodophenyl)pentadecanoic acid (IPPA) in their ability to be taken up and retained by the rat myocardium.

  15. A survey of owners' perceptions and experiences of radioiodine treatment of feline hyperthyroidism in the UK. (United States)

    Boland, Lara A; Murray, Jane K; Bovens, Catherine Pv; Hibbert, Angie


    The efficacy of radioiodine treatment of feline hyperthyroidism is well established; however, limited information is known about owners' perceptions or experiences of radioiodine. This study aimed to examine factors that influence owner treatment choices and their opinions following radioiodine. Surveys were sent to owners of cats referred for radioiodine treatment between 2002 and 2011 (radioiodine group; 264 cats) and owners of non-radioiodine-treated hyperthyroid cats seen at first-opinion practices (control group; 199 cats). The response rate was 67.0% (310 returned: 175 radioiodine, 135 control). Of 135 controls, 72 (53.3%) were unaware of radioiodine as a treatment option. Owners of cats ⩾15 years old and uninsured cats were less likely to pursue radioiodine. Cost of treatment, travel distance, potential human or animal health risks and waiting periods for radioiodine had a low impact on owners' treatment choice. Owners reported a moderate level of concern about treatment hospitalisation length, which included (158 respondents) the possibility of the cat being unhappy 130 (82.3%), owner missing the cat 102 (64.6%), inappetence 50 (31.6%), other pets missing the cat 32 (20.3%), development of co-morbid disease 28 (17.7%) and side effects 25 (15.8%). Owners assessed their cat's quality of life on a scale of 1 (very poor) to 10 (excellent), as 4 (4) (median [interquartile range]) pre-radioiodine (134 respondents) and 9 (2) post-radioiodine (131 respondents). Of 132 respondents, 121 (91.7%) were happy with their decision to choose radioiodine. The results of this questionnaire may assist veterinarians in addressing common owner concerns when discussing radioiodine as a treatment option for hyperthyroidism. © ISFM and AAFP 2014.

  16. Radioiodine therapy and subsequent pregnancy; Gravidez apos radioiodoterapia

    Energy Technology Data Exchange (ETDEWEB)

    Brandao, Carmen Dolores G.; Miranda, Angelica E.; Corres, Nilson Duarte; Sieiro Neto, Lino; Corbo, Rossana; Vaisman, Mario [Hospital Universitario Clementino Fraga Filho (UFRJ), Rio de Janeiro, RJ (Brazil). Dept. of Endocrinology and Nuclear Medicine; Instituto Nacional do Cancer (INCa), Rio de Janeiro, RJ (Brazil); Hospital dos Servidores do Estado do Rio de Janeiro, RJ (Brazil); E-mail:


    Objectives: To evaluate abortion and fetal congenital anomaly rates in women previously submitted to radioiodine therapy for differentiated thyroid carcinoma. Study design: A case-control study of 108 pregnant women, 48 cases whose pregnancies were evaluated after they had undergone radioiodine therapy for differentiated thyroid carcinoma, and the control group consisted of 60 healthy pregnant women. Results: Of a total of 66 pregnancies, 14 conceived within the first year, 51 one or more years after the last administration of {sup 131}I, the medical record of one patient was not available. The interval between the last radioiodine therapy administration and conception ranged from 1 month to 10 years. There were a total of 4 miscarriages, 2 of them for unknown reasons. There was one case of congenital anomaly and two preterms birth. Nine women presented the following pregnancy events: placental insufficiency, hypertensive crisis, placental detachment, risk of miscarriage, preterm labour and four miscarriages. No statistical difference was observed between the studied and control groups. Conclusion: Radioiodine was followed by no significant increase in untoward effects in neither the pregnancy nor the offspring. (author)

  17. ORIGINAL ARTICLE ORI ORI Radioiodine therapy in skeletal ...

    African Journals Online (AJOL)

    sentation to the thyroid clinic, and 7 at follow-up. Patients' ages ranged from 30 - 77 ... cancer clinic, which is part of the Division of Nuclear Medicine. Twenty-. Radioiodine therapy in ..... Papillary thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome.

  18. Guidelines for radioiodine therapy of differentiated thyroid cancer.

    NARCIS (Netherlands)

    Luster, M.; Clarke, S.E.; Dietlein, M.; Lassmann, M.; Lind, P.; Oyen, W.J.G.; Tennvall, J.; Bombardieri, E.


    INTRODUCTION: The purpose of the present guidelines on the radioiodine therapy (RAIT) of differentiated thyroid cancer (DTC) formulated by the European Association of Nuclear Medicine (EANM) Therapy Committee is to provide advice to nuclear medicine clinicians and other members of the DTC-treating

  19. Dosage assessment for radioiodine therapy in benign thyroid disorders

    NARCIS (Netherlands)

    Isselt, J.W. van


    The general aim of this thesis was to investigate the value and the shortcomings of the becquerel-per-gram method for radioiodine therapy in various benign thyroid disorders. The history of this treatment form, which goes back to the late 1940s, is described in Chapter 1. Almost fifty years after

  20. A New Technology Developed to Remove Aqueous Radioiodine

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Yeop; Baik, Min Hoon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)


    Radioiodine is considered as a critical radionuclide by the International Commission on Radiological Protection(ICRP) in terms of the radiation and radiotoxicity risks to nature and human health. In addition, there were reports about great increases of thyroid cancer in children in Belarus from 1990. In natural environments, there were several reports for the unusual increase of radioactive iodine ratios in most environmental samples (i.e. soils, vegetables, and seafoods). Iodine usually exists as iodide, iodate, and organic iodine in the environment. Iodide is considered as the most difficult form among the iodine species to treat by the conventional adsorption-based technology. This is why urgent new technology is needed to suppress such a progressive accumulation of radioiodine in natural environments. The conventional methods based on the anion-exchange and adsorption techniques have been difficult to manage the growing release of radioiodine for decades. Here we suggest a new solution that uses a biostimulant way to isolate radioiodine. We discovered that natural SRB can play an important intermediary role to get anionic iodide and cationic copper combined strongly as perfect counterions by enzymatic Cu-reduction.

  1. Radioiodine therapy versus antithyroid medications for Graves' disease. (United States)

    Ma, Chao; Xie, Jiawei; Wang, Hui; Li, Jinsong; Chen, Suyun


    Graves' disease is the most common cause of hyperthyroidism. Both antithyroid medications and radioiodine are commonly used treatments but their frequency of use varies between regions and countries. Despite the commonness of the diagnosis, any possible differences between the two treatments with respect to long-term outcomes remain unknown. To assess the effects of radioiodine therapy versus antithyroid medications for Graves' disease. We performed a systematic literature search in the Cochrane Library, MEDLINE and EMBASE and the trials registers ICTRP Search Portal and The date of the last search was September 2015 for all databases. Randomised controlled trials (RCTs) comparing the effects of radioiodine therapy versus antithyroid medications for Graves' disease with at least two years follow-up. Two authors independently screened titles and abstracts for relevance. One author carried out screening for inclusion, data extraction and 'Risk of bias' assessment and a second author checked this. We presented data not suitable for meta-analysis as descriptive data. We analysed the overall quality of evidence utilising the GRADE instrument. We included two RCTs involving 425 adult participants with Graves' disease in this review. Altogether 204 participants were randomised to radioiodine therapy and 221 to methimazole therapy. A single dose of radioiodine was administered. The duration of methimazole medication was 18 months. The period of follow-up was at least two years, depending on the outcome measured. For most outcome measures risk of bias was low; for the outcomes health-related quality of life as well as development and worsening of Graves' ophthalmopathy risks of performance bias and detection bias were high in at least one of the two RCTs.Health-related quality of life appeared to be similar in the radioiodine and methimazole treatment groups, however no quantitative data were reported (425 participants; 2 trials; low quality evidence

  2. Indications for radioiodine administration in follicular-derived thyroid cancer. (United States)

    Buffet, C; Ghander, C; le Marois, E; Leenhardt, L


    Indications for radioiodine administration after thyroid cancer surgery have shifted in recent years toward personalized management, adapted to the individual risk of tumor progression. The most recent guidelines and studies favor de-escalation in indications for administration, dosage and means of preparation with exogenous recombinant TSH stimulation as treatment of choice. Radioiodine administration has 3 possible objectives: • ablation of normal thyroid tissue remnants in patients with low risk of progression, using low radioiodine activity levels, with the advantage of completing disease staging on whole-body scintigraphy performed after administration of the radioiodine capsule, and of facilitating follow-up by thyroglobulin assay; • adjuvant treatment for suspected microscopic metastases in patients with intermediate or high risk of progression, using higher activity levels, with the theoretic aim of limiting recurrence and mortality; • curative treatment in high-risk patients with proven metastases, using exclusively high activity levels, with a view to improving specific survival. In future, indications for ablation and/or activity prescription may be governed by an algorithm incorporating individual baseline progression risk (essentially founded of pTNM staging) and postoperative data such as thyroglobulin level and neck ultrasound results. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. Turbulent transfer characteristics of radioiodine effluents from air to grass

    Energy Technology Data Exchange (ETDEWEB)

    Markee, E.H. [ARFRO, Environmental Science Services Administration, Idaho Falls, Idaho (United States)


    A total of 20 controlled field releases of radioiodine have been performed at the National Reactor Testing Station in Idaho as a portion of a program to study the transmission of gaseous radioiodine through the air-vegetation-cow-milk-human chain. Most of the releases were conducted over typical pasture grasses during different wind and stability conditions. Radioiodine adherence to grass and carbon plates was measured during most of the tests. Vertical air concentration profiles and turbulence parameters were measured to determine flux characteristics. Analysis of the data reveals the complex interdisciplinary nature of transfer of radioiodine from air to a natural surface. The data are in reasonable agreement with the deposition models of Sheppard and Chamberlain when corrections for the physical and biological receptiveness of the grass and grass density are made. The average ratios of momentum to mass flux were found to be 0.9 in stable conditions and 1.4 in unstable conditions. These ratios demonstrate the effect on mass flux in the lowest 4m by a surface that acts as a partial sink for gaseous effluents. This series of releases indicates the need for further research on the biological receptiveness of grass and turbulent transfer within a grass canopy. (author)


    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, D.; Emerson, H.; Powell, B.; Roberts, K.; Zhang, S.; Xu, C.; Schwer, K.; Li, H.; Ho, Y.; Denham, M.; Yeager, C.; Santschi, P.


    Iodine-129 is one of the key risk drivers for several Savannah River Site (SRS) performance assessments (PA), including that for the Low-Level Waste Disposal Facility in E-Area. In an effort to reduce the uncertainty associated with the conceptual model and the input values used in PA, several studies have recently been conducted dealing with radioiodine geochemistry at the SRS. The objective of this report was to review these recent studies and evaluate their implications on SRS PA calculations. For the first time, these studies measured iodine speciation in SRS groundwater and provided technical justification for assuming the presence of more strongly sorbing species (iodate and organo-iodine), and measured greater iodine sediment sorption when experiments included these newly identified species; specifically they measured greater sorption coefficients (K{sub d} values: the concentration ratio of iodine on the solid phase divided by the concentration in the aqueous phase). Based on these recent studies, new best estimates were proposed for future PA calculations. The new K{sub d} values are greater than previous recommended values. These proposed K{sub d} values reflect a better understanding of iodine geochemistry in the SRS subsurface environment, which permits reducing the associated conservatism included in the original estimates to account for uncertainty. Among the key contributing discoveries supporting the contention that the K{sub d} values should be increased are that: 1) not only iodide (I{sup -}), but also the more strongly sorbing iodate (IO{sub 3}{sup -}) species exists in SRS groundwater (average total iodine = 15% iodide, 42% iodate, and 43% organoiodine), 2) when iodine was added as iodate, the measured K{sub d} values were 2 to 6 times greater than when the iodine was added as iodide, and perhaps most importantly, 3) higher desorption (10 to 20 mL/g) than (ad)sorption (all previous studies) K{sub d} values were measured. The implications of this

  5. Target therapies for radioiodine refractory advanced thyroid tumors. (United States)

    Schlumberger, M


    A small but not irrelevant percentage of differentiated thyroid cancers become refractory to radioiodine treatment either because they lose the ability of taking up iodine over the time or because, despite a persistent uptaking ability, the effect of the radioiodine is lost in terms of tumor burden reduction. These patients receive only few and transient benefits from other conventional therapies and particularly from chemotherapy. In the last decade, several new drugs have been discovered as potentially useful and tested in clinical trials. They are mainly represented by protein kinase inhibitor molecules that should be proposed to advanced and progressive 131I refractory thyroid cancer patients by enrolling them in clinical trials or by the "off label" use of the drug.

  6. A radioiodinated biocytin derivative for in-vivo applications. (United States)

    Nakamoto, Y; Sakahara, H; Saga, T; Yao, Z; Zhang, M; Sato, N; Zhao, S; Arano, Y; Ono, M; Saji, H; Konishi, J


    Radioiodinated biocytin derivatives are potentially useful for multi-step tumour targeting using the avidin-biotin system. We synthesized a radioiodinated biocytin derivative and evaluated its properties in vivo. We labelled biocytin with 125I by coupling biocytin to radioiodinated N-succinimidyl 3-(tri-n-butyl-stannyl) benzoate, and assessed its binding to avidin and its biodistribution in normal and tumour-bearing mice. When the synthesized biocytin was incubated with immobilized avidin, more than 94% of the radioactivity was bound. However, after 2 h incubation in serum, only 40% of the radioactivity was bound to the avidin. The iodinated biocytin derivative was characteristically taken up by the liver and the kidneys when injected intravenously into mice. In mice bearing an intraperitoneal tumour xeno-graft, 125I-biocytin and 111In-biotin were co-injected intraperitoneally 4 h after the intraperitoneal administration of avidin, which accumulated in the intraperitoneal tumours. At 2 and 24 h, the tumour uptake of 125I-biocytin was 8.2 and 3.8% ID/g respectively, whereas that of 111In-biotin was 20.0 and 18.7% ID/g respectively. When radioiodinated, biocytin retains its binding capacity to avidin, and it localizes well with high tumour-to-normal tissue ratios early post-injection using the two-step method, but compared to 111In-biotin it is unstable. We conclude that the stability of the product in serum needs to be improved prior to in-vivo applications.

  7. Dry Distillation of Radioiodine from TeO2 Targets

    Directory of Open Access Journals (Sweden)

    Jacek Koziorowski


    Full Text Available As medical cyclotrons are becoming more abundant, 123I and 124I are getting more attention as alternatives to 131I for diagnostics of thyroid disease. Both 123I and 124I provide better diagnostics, deliver less dose to patients and both reduce the risk of thyroid stunning, facilitating subsequent therapy. Dry distillation of radioiodine from tellurium dioxide targets has become the standard approach to producing these radioiodines. Setting up such a production of radioiodine is associated with a lengthy optimization of the process and for this purpose natural tellurium is often used for economical reasons. In this paper, the distillation parameters are scrutinized to ensure optimal distillation temperature, in order to minimize time spent and prevent loss of expensive target material. It is further demonstrated how the individual iodine isotopes, produced from proton bombardment of natTe, will diffuse out of the target in a time dependent ratio. We believe the effect is due to the isotopes having their maximum cross section at different energies. The individual isotopes produced will thus have their highest concentration at different depths in the target. This results in individual mean diffusion lengths and diffusion times for the different isotopes.

  8. Radioiodine Therapy Does Not Change the Atherosclerotic Burden of the Carotid Arteries

    DEFF Research Database (Denmark)

    La Cour, Jeppe Lerche; Andersen, Ulrik Bjørn; Sørensen, Christian Hjort


    BACKGROUND AND AIM: Atherosclerosis evolves or accelerates when arteries are exposed to ionizing radiation, both early and late after exposure. Radioiodine therapy of benign thyroid disease exposes the carotid arteries to 4-50 Gy, and may thereby increase the risk of atherosclerosis. Increased risk...... of cerebrovascular events has been reported after radioiodine therapy. This study aimed to examine whether atherosclerosis develops early or late after radioiodine therapy of benign thyroid disease. METHOD: Patients treated for benign thyroid disorders (nontoxic goiter, adenoma, and hyperthyroidism) were examined...... with ultrasound for the main outcome, carotid intima media thickness (CIMT), and for plaque presence (plaque presence only in late damage). Signs of early damage from radioiodine were studied in 39 radioiodine-treated patients, who were examined before treatment and at 1, 3, 6, and 12 months after treatment. Late...

  9. Experiment and DFT studies on radioiodine removal and storage mechanism by imidazolium-based ionic liquid. (United States)

    Cao, Bobo; Liu, Shuangyue; Du, Dongmei; Xue, Zhimin; Fu, Hui; Sun, Haitao


    In order to remove and store radioactive substances effectively, studies on the mechanisms of radioiodine captured by ionic liquids (ILs) with a fixed cation (1-butyl-3-methyl-imidazolium cation [Bmim]+) were carried out in experimental and theoretical methods. Fourier transform infrared attenuated total reflectance (FT-IR ATR) spectra of 2BP8HQ and ultraviolet-visible (UV/vis) spectroscopy were used to investigate the kinetic process of radioiodine removal by ILs in experiment. Corresponding theoretical investigations on the structures and formation mechanisms of ILs, bare anions and complexes as well as hydrogen bonds was carried using density functional theory. The electrostatic potential was used in configuration design and construction. Charge distribution was used to show the variation of atom charge density, Interaction energy and vibration frequency change were performed to explore possible mechanisms on the halogen bond formation between radioiodine molecule and bare anion or anion in ILs when radioiodine captured by ILs. In order to characterize halogen bonds both natural bond orbital analysis and atoms in molecules analysis were performed. Both experimental and computational results showed that radioiodine could be captured by ILs with a 1:1mol stoichiometry. It was noteworthy that [Bmim][Br], [Bmim][I] and [Bmim][Cl], containing high radioiodine capture efficiency anions, were better candidates in removal and reliable storage of radioiodine for their capture efficiencies of over 80% in 5h. Copyright © 2016. Published by Elsevier Inc.

  10. Testicular function after radioiodine therapy for thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wichers, M.; Benz, E.; Klingmueller, D. [Dept. of Clinical Biochemistry, University of Bonn, Bonn (Germany); Palmedo, H.; Biersack, H.J. [Dept. of Nuclear Medicine, University of Bonn, Bonn (Germany); Gruenwald, F. [Dept. of Nuclear Medicine, University of Frankfurt, Frankfurt (Germany)


    Radiotherapy can cause infertility in both men and women. However, few data are available concerning the effects of radioiodine therapy for thyroid carcinoma on testicular function. We investigated 25 men (age 23-73 years) with differentiated thyroid carcinoma in a longitudinal prospective trial. Follicle-stimulating hormone (FSH), inhibin B, luteinising hormone (LH) and testosterone were measured before (n=25) and 3 months (n=11), 6 months (n=18), 12 months (n=22), and 18 months (n=18) after radioiodine therapy [radioiodine dose (mean {+-} SEM): 9.8{+-}0.89 GBq]. Before therapy, FSH was 5.4{+-}0.77 IU/l; it increased significantly (P<0.001) to 21.3{+-}2.4 IU/l after 6 months and fell to 7.4{+-}1.3 IU/l after 18 months (normal range: 1.8- 9.2 IU/l). Inhibin B was significantly decreased (P<0.001) from 178{+-}25.3 pg/ml before therapy to 22.2{+-}5.5 pg/ml after 3 and 29.4{+-}5.7 pg/ml after 6 months and rose to 154{+-}23.3 pg/ml after 18 months (normal range 75- 350 pg/ml). LH and testosterone were within the normal range during the whole study (1.6-9.2 IU/l and 10.4-34.7 nmol/l, respectively). LH was significantly increased (P<0.001) from 2.8{+-}0.33 IU/l before therapy to 5.9{+-}0.69 IU/l 6 months after therapy and then fell slowly to 4.0{+-}0.45 IU/l after 18 months. Total testosterone was significantly increased (P<0.01) from 12.8{+-}0.99 nmol/l at baseline to 19.8{+-}1.7 nmol/l after 12 months and 19.6{+-}1.7 nmol/l after 18 months. The testosterone/LH ratio (normal range: 3.3-17.9 nmol/IU) fell from 5.8{+-}0.66 nmol/IU to 3.0{+-}0.36 nmol/IU after 3 months (P<0.01); it remained close to the latter value after 6 months (3.4{+-}0.49 nmol/IU) and then rose to 5.5{+-} 0.6 nmol/IU after 18 months. In conclusion, 3 and 6 months after radioiodine therapy all patients showed elevated FSH and decreased inhibin B levels, reflecting severely impaired spermatogenesis. At the same time a compensated insufficiency of the Leydig cell function was observed. Eighteen months

  11. [Results of individually adjusted radioiodine treatment of hyperthyroidism.]. (United States)

    Sigthorsson, G; Kjeld, M


    Radioiodine (131I) treatment was started in Iceland in 1960 and the same formula has been used from the beginning to calculate the doses of radioactivity aiming for 70 Gy irradiation of the gland. In the present investigation we studied 468 patients who were treated over a period of 19 years (1973-1991). About 90% of the patients had Graves' disease (GD), 9% toxic adenoma but less than 1% toxic multinodular goiter. Approximately 70% of the GD patients became hypothyroid (subclinical hypothyroidism included) within the first year after a single radioiodine treatment and about 80% were hypothyroid four years after treatment with no significant increase after that. By contrast, only one of 15 patients with toxic adenoma became hypothyroid after a single treatment. For both groups the recurrence rate of hyperthyroidism was approximately 20%. The formula used for dose calculation in this study for GD patients does not seem to be satisfactory. The smaller glands are getting to much irradiation and the larger glands to little as can be seen by the frequency of hypothyroidism in the smaller glands and recurrences (continuing hyperthyroidism) in the larger glands after one treatment (table V). In 1993 blood samples were obtained from a sample group (n=103) of once 131I treated GD patients and measurements were done for serum TSH, T4 and free T4. One third of the patients who were considered euthyroid, and therefore not taking T4, were found to be hypothyroid with elevated TSH and low FT4 and one third of those taking T4 seemed to be overtreated with elevated FT4 and decreased TSH levels. It is concluded that the results of the radioiodine treatment for GD are unsatisfactory and need to be changed, either by adjusting the present regimen so that radiation is decreased in the smaller glands but increased in the larger ones or alternatively, by increasing the radiation dose to all the glands rendering the majority of the patients quickly hypothyroid followed by replacement

  12. Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation (United States)

    Chakravarty, Debyani; Santos, Elmer; Ryder, Mabel; Knauf, Jeffrey A.; Liao, Xiao-Hui; West, Brian L.; Bollag, Gideon; Kolesnick, Richard; Thin, Tin Htwe; Rosen, Neal; Zanzonico, Pat; Larson, Steven M.; Refetoff, Samuel; Ghossein, Ronald; Fagin, James A.


    Advanced human thyroid cancers, particularly those that are refractory to treatment with radioiodine (RAI), have a high prevalence of BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations. However, the degree to which these cancers are dependent on BRAF expression is still unclear. To address this question, we generated mice expressing one of the most commonly detected BRAF mutations in human papillary thyroid carcinomas (BRAFV600E) in thyroid follicular cells in a doxycycline-inducible (dox-inducible) manner. Upon dox induction of BRAFV600E, the mice developed highly penetrant and poorly differentiated thyroid tumors. Discontinuation of dox extinguished BRAFV600E expression and reestablished thyroid follicular architecture and normal thyroid histology. Switching on BRAFV600E rapidly induced hypothyroidism and virtually abolished thyroid-specific gene expression and RAI incorporation, all of which were restored to near basal levels upon discontinuation of dox. Treatment of mice with these cancers with small molecule inhibitors of either MEK or mutant BRAF reduced their proliferative index and partially restored thyroid-specific gene expression. Strikingly, treatment with the MAPK pathway inhibitors rendered the tumor cells susceptible to a therapeutic dose of RAI. Our data show that thyroid tumors carrying BRAFV600E mutations are exquisitely dependent on the oncoprotein for viability and that genetic or pharmacological inhibition of its expression or activity is associated with tumor regression and restoration of RAI uptake in vivo in mice. These findings have potentially significant clinical ramifications. PMID:22105174

  13. Characterization and restoration of performance of {open_quotes}aged{close_quotes} radioiodine removing activated carbons

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, W.P. [NUCON International, Inc., Columbus, OH (United States)


    The degradation of radioiodine removal performance for impregnated activated carbons because of ageing is well established. However, the causes for this degradation remain unclear. One theory is that this reduction in performance from the ageing process results from an oxidation of the surface of the carbon. Radioiodine removing activated carbons that failed radioiodine removal tests showed an oxidized surface that had become hydrophilic compared with new carbons. We attempted to restore the performance of these {open_quotes}failed{close_quotes} carbons with a combination of thermal and chemical treatment. The results of these investigations are presented and discussed with the view of extending the life of radioiodine removing activated carbons. 4 refs., 2 tabs.

  14. The Effect of High Dose Radioiodine Therapy on Formation of Radiation Retinopathy During Thyroid Cancer Treatment


    Tülay Kaçar Güvel; Sezer Özkan; Müge Öner Tamam


    Objective: Non-thyroidal complication of high-dose radioiodine therapy for thyroid carcinoma might cause salivary and lacrimal gland dysfunction, which may be transient or permanent in a dose-dependent manner. However, radiation retinopathy complicating 131I therapy, has not been previously well characterized. The aim of this study was to evaluate the extent of retinal damage among patients who had received high doses of radioiodine treatment. Methods: Forty eyes of 20 patients (3 male, 17 fe...

  15. Toxoplasma gondii: demonstration of intrinsic peroxidase activity during lacto-peroxidase mediated radioiodination of tachyzoites

    Energy Technology Data Exchange (ETDEWEB)

    Gallois, Y.; Tricaud, A.; Foussard, F.; Hodbert, J.; Girault, A.; Mauras, G.; Dubremetz, J.F.


    Tachyzoites of Toxoplasma gondii have been radioiodinated under various conditions with or without lactoperoxidase, with glucose oxidase being used to generate hydrogen peroxide. Erythrocytes were iodinated simultaneously as a control. In our conditions, tachyzoites were more intensely labelled in the absence of lactoperoxidase. This result can be explained by the existence of an intrinsic peroxidase activity which interfere with the exogenously added enzyme during surface radioiodination.

  16. Radioiodine therapy in patients with Graves' disease and the effects of prior carbimazole therapy. (United States)

    Karyampudi, Arun; Hamide, Abdoul; Halanaik, Dhanapathi; Sahoo, Jaya Prakash; Kamalanathan, Sadishkumar


    The use of radioiodine as the first line of treatment in Graves' disease is restricted in India because of its limited availability and an unrealistic risk perception associated with it. Additionally, the effectiveness of radioiodine ablation in Graves' disease is influenced by many factors. Prior medical antithyroid therapy is one such important factor. To analyze the efficacy of low dose radioiodine therapy (5 mCi) in treatment of naive patients of Graves' disease in comparison to that in which it was already primed with an antithyroid drug, carbimazole. A non-randomized, interventional study conducted in the Department of Medicine and Endocrinology of a tertiary care institute in South India. The study had two groups; Group A (36 treatment naive, uncomplicated Graves' disease patients) and B (34 Graves' disease patients on carbimazole prior to radioiodine therapy). Both groups had baseline clinical, biochemical evaluation and were reassessed at 3 and 6 months for evaluating the clinical status for possible documentation of cure. The cure rate was 61.1% in drug naive group and 58.8% in pretreated group at 6 months following radioiodine (P = 0.845). Higher baseline 999m technicium (99m Tc) uptake, male gender, BMI and higher baseline free thyroxine (fT4) level predicted treatment failure following radioiodine therapy. Administration of carbimazole prior to low dose radioiodine therapy does not alter the efficacy of radioiodine. Low fixed dose (5 mCi) of radioactive iodine may be a safe and effective primary therapeutic option in Graves' disease patients pretreated with antithyroid drugs.

  17. Selective mono-radioiodination and characterization of a cell-penetrating peptide. L-Tyr-maurocalcine

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadi, Mitra; Bacot, Sandrine; Perret, Pascale; Riou, Laurent; Ghezzi, Catherine [Universite Joseph Fourier, Grenoble (France); INSERM U1039, Grenoble (France). Radiopharmaceutiques Biocliniques; Poillot, Cathy; Cestele, Sandrine [INSERM U836, Grenoble (France). Grenoble Inst. of Neuroscience; Universite Joseph Fourier, Grenoble (France); Desruet, Marie-Dominique [INSERM U1039, Grenoble (France). Radiopharmaceutiques Biocliniques; Couvet, Morgane; Bourgoin, Sandrine; Seve, Michel [CRI-INSERM U823, Grenoble (France). Inst. of Albert Bonniot; Universite Joseph Fourier, Grenoble (France); Waard, Michel de [INSERM U836, Grenoble (France). Grenoble Inst. of Neuroscience; Universite Joseph Fourier, Grenoble (France); Smartox Biotechnologies, Grenoble (France)


    Mono-and poly-iodinated peptides form frequently during radioiodination procedures. However, the formation of a single species in its mono-iodinated form is essential for quantitative studies such as determination of tissue concentration or image quantification. Therefore, the aim of the present study was to define the optimal experimental conditions in order to exclusively obtain the mono-iodinated form of L-maurocalcine (L-MCa). L-MCa is an animal venom toxin which was shown to act as a cell-penetrating peptide. In order to apply the current direct radioiodination technique using oxidative agents including chloramine T, Iodo-Gen {sup registered} or lactoperoxidase, an analogue of this peptide containing a tyrosine residue (Tyr-L-MCa) was synthesized and was shown to fold/oxidize properly. The enzymatic approach using lactoperoxidase/H{sub 2}O{sub 2} was found to be the best method for radioiodination of Tyr-L-MCa. MALDI-TOF mass spectrometry analyses were then used for identification of the chromatographic eluting components of the reaction mixtures. We observed that the production of different radioiodinated species depended upon the reaction conditions. Our results successfully described the experimental conditions of peptide radioiodination allowing the exclusive production of the mono-iodinated form with high radiochemical purity and without the need for a purification step. Mono-radioiodination of L-Tyr-MCa will be crucial for future quantitative studies, investigating the mechanism of cell penetration and in vivo biodistribution.

  18. Variants and pitfalls on radioiodine scans in pediatric patients with differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Mostafa, Mohamed; Vali, Reza; Chan, Jeffrey; Omarkhail, Yusuaf; Shammas, Amer [University of Toronto, Nuclear Medicine Division, Department of Medical Imaging, The Hospital for Sick Children, Toronto, Ontario (Canada)


    Potentially false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma can mimic functioning thyroid tissue and functioning thyroid carcinomatous tissue. Such false-positive findings comprise variants and pitfalls that can vary slightly in children as compared with adults. To determine the patterns and frequency of these potential false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma. We reviewed a total of 223 radioiodine scans from 53 pediatric patients (mean age 13.3 years, 37 girls) with differentiated thyroid carcinoma. Focal or regional activity that likely did not represent functioning thyroid tissue or functioning thyroid carcinomatous tissue were categorized as variants or pitfalls. The final diagnosis was confirmed by reviewing the concurrent and follow-up clinical data, correlative ultrasonography, CT scanning, serum thyroglobulin and antithyroglobulin antibody levels. We calculated the frequency of these variants and pitfalls from diagnostic and post-therapy radioiodine scans. The most common variant on the radioiodine scans was the thymic activity (24/223, 10.8%) followed by the cardiac activity (8/223, 3.6%). Salivary contamination and star artifact, caused by prominent thyroid remnant, were the most important observed pitfalls. Variants and pitfalls that mimic functioning thyroid tissue or functioning thyroid carcinomatous tissue on radioiodine scan in children with differentiated thyroid carcinoma are not infrequent, but they decrease in frequency on successive radioiodine scans. Potential false-positive findings can be minimized with proper knowledge of the common variants and pitfalls in children and correlation with clinical, laboratory and imaging data. (orig.)

  19. Radioiodine scan index: A simplified, quantitative treatment response parameter for metastatic thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jong Ryool; Ahn, Byeong Cheol; Jeong, Shin Young; Lee, Sang Woo; Lee, Jae Tae [Dept. of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu (Korea, Republic of)


    We aimed to develop and validate a simplified, novel quantification method for radioiodine whole-body scans (WBSs) as a predictor for the treatment response in differentiated thyroid carcinoma (DTC) patients with distant metastasis. We retrospectively reviewed serial WBSs after radioiodine treatment from 2008 to 2011 in patients with metastatic DTC. For standardization of TSH simulation, only a subset of patients whose TSH level was fully enhanced (TSH > 80 mU/l) was enrolled. The radioiodine scan index (RSI) was calculated by the ratio of tumor-to-brain uptake. We compared correlations between the RSI and TSH-stimulated serum thyroglobulin (TSH{sub sT}g) level and between the RSI and Tg reduction rate of consecutive radioiodine treatments. A total of 30 rounds of radioiodine treatment for 15 patients were eligible. Tumor histology was 11 papillary and 4 follicular subtypes. The TSH{sub sT}g level was mean 980 ng/ml (range, 0.5–11,244). The Tg reduction rate after treatment was a mean of −7 % (range, −90 %–210 %). Mean RSI was 3.02 (range, 0.40–10.97). RSI was positively correlated with the TSH{sub sT}g level (R2 = 0.3084, p = 0.001) and negatively correlated with the Tg reduction rate (R2 = 0.2993, p = 0.037). The regression equation to predict treatment response was as follows: Tg reduction rate = −14.581 × RSI + 51.183. Use of the radioiodine scan index derived from conventional WBS is feasible to reflect the serum Tg level in patients with metastatic DTC, and it may be useful for predicting the biologic treatment response after radioiodine treatment.

  20. Response of thyroglobulin to radioiodine therapy in thyroglobulin-elevated negative iodine scintigraphy (TENIS) syndrome. (United States)

    Sinha, Partha; Conrad, Gary R; West, Hollie C


    While radioiodine (131-I) is widely used in the treatment of differentiated thyroid cancer, its role remains less certain when abnormal 131-I uptake cannot be demonstrated in a pre-therapy diagnostic scan. Documentation of abnormal 131-I uptake in a post-therapy scan in such cases helps to justify the radioiodine therapy, but the post-therapy scan can remain persistently negative. To evaluate (i) whether 131-I therapy had any measurable effect on thyroglobulin (Tg) levels in patients who were scan negative prior to radioiodine therapy and remained scan negative after therapy, and (ii) whether the magnitude of the effect on Tg depended on the pre-therapy Tg level. Retrospective analysis of 78 patients. All patients had pre-therapy and post-therapy Tg levels measured under stimulation with thyroid stimulating hormone. Hospital data until date of last contact were analyzed to assess for recurrent disease. Tg levels decreased by 55% in those having Tg 10 μg/l or higher; and by 41% in those with less than 10 μg/l. In patients with detectable Tg antibodies, there were no statistically significant decreases demonstrated for either Tg or Tg antibody levels. Radioiodine therapy can reduce Tg levels, independently of the pre-therapy level, even when the pre-therapy level is low and the pre-therapy, as well as the post-therapy, radioiodine scan remains negative.

  1. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Byeong-Cheol Ahn


    Full Text Available Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term “theranostics” was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging.

  2. Radioiodinated carnitine and acylcarnitine analogs as potential myocardial imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    McConnell, D.S.


    R-carnitine is extremely important in mammalian energy metabolism. Gamma-butyrobetaine, the immediate biosynthetic precursor to R-carnitine, is synthesized in many organs. However, only liver can hydroxylate gamma-butyrobetaine to carnitine. Thus the transport of carnitine from its site of synthesis to the site of utilization is of utmost importance. Carnitine is found in highest concentration in cardiac and skeletal muscle, where it is required for the transport of fatty acids into the mitochondria. Before fatty acids are utilized as fuel for the myocyte by beta-oxidation, they are bound to carnitine as an acylcarnitine ester at the 3-hydroxyl, and transported across the micochondrial membranes. R,S-Carnitine has been shown to be taken up by myocytes. The author has begun a study on the use of carnitine derivatives as potential carriers for the site-specific delivery of radioiodine to bidning sites in the myocardium. Such agents labeled with a gamma-emitting nuclide such as iodine-123 would be useful for the noninvasive imaging of these tissues. The aim was to synthesize a variety of radiolabeled analogs of carnitine and acylcarnitine to address questions of transport, binding and availability for myocardial metabolism. These analogs consist of N-alkylated derivatives of carnitine, acylcarnitine esters as well as carnitine amides and ethers. One C-alkylated derivative showed interesting biodistribution, elevated myocardial uptake and competition with carnitine for binding in the myocardium.

  3. Improved radioiodination of biomolecules using exhaustive Chloramine-T oxidation. (United States)

    Robles, A M; Balter, H S; Oliver, P; Welling, M M; Pauwels, E K


    To improve standardization in analytical reagents we investigated Chloramine-T radioiodination (125I) of several biomolecules based on the use of a single amount of the oxidizing agent Chloramine-T as the limiting reagent being exhausted during the course of the reaction. Whenever the labeling yield resulted in less than one atom 125I/molecule, a second amount of the oxidizing agent was added. Thereafter, the integrity of the various biomolecules was assessed using radioimmunoassays, radioreceptor binding assays, or radioimmunometric assays. Purification yields were done by gel permeation (56% +/- 19%, n=230) or by precipitation with trichloroacetic acid (59% +/- 19%, n=230). Specific activity (117 +/- 61 MBq/nmol) and the degree of iodine incorporation (1.4 +/- 0.8 atoms of 125I/molecule) were achieved after 300 sec of incubation. A second addition of Chloramine-T resulted in an increased labeling yield of all biomolecules tested by a mean factor of 1.8 +/- 0.9. After the second addition of Chloramine-T, we observed for some biomolecules a significant (pChloramine-T as a limiting reagent resulted in molecules with appropriate immunological and biological performance. In general, tracers were minimally damaged and assessment of the shelf life as well as storing conditions showed the usefulness of the standardization of biomolecule labeling.

  4. Protein radioiodination in a radioassay laboratory: evaluation of commercial Na/sup 125/I reagents and related biohazards

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, R.G.; Button, T.M.


    Three commercial Na/sup 125/I solutions (Amersham, New England Nuclear, and Union Carbide) have been examined with respect to multiple parameters affecting their use in the radioiodination of three representative peptides (insulin, growth hormone, and gastrin): % of radioiodine incorporation in protein; immunoreactivity and non-specific binding properties of the radiolabeled proteins; pH, volatility, and radionuclidic purity of radioiodine solutions; and vial construction with respect to multidose use. All three commercial Na/sup 125/I produced radioiodinated proteins of good quality for use in radioligand assays. The radioiodines differed with respect to the amount of iodine released during initial vial opening as a consequence of different pH levels. Two of the three products were shipped in vials with poor construction with respect to multidose use. Selection of a radioiodine was therefore reduced to the secondary considerations of iodine volatility and vial construction. The volatilized radioiodine observed during the spill of millicuries quantities of unbuffered pH 7.5 Na/sup 125/I was 14 microcuries per millicurie within the first 30 minutes. One thickness of rubber gloves reduced potential skin contamination from an accidental spill to insignificant levels: 20-30 picocuries per microcurie. Common good housekeeping procedures: i.e. rubber gloves, laboratory coat and a fume hood were found to be sufficient protection to eliminate most radioiodine volatility and contamination hazards associated with protein radiolabeling procedures.

  5. Radioiodine concentration by the thymus in differentiated thyroid carcinoma: report of five cases

    Energy Technology Data Exchange (ETDEWEB)

    Mello, Maria Eduarda; Flamini, Rodrigo C.; Corbo, Rossana; Mamede, Marcelo [Instituto Nacional do Cancer (INCa), Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear], e-mail:


    The radioactive iodine has been used with great value as a diagnostic and therapeutic method in patients with differentiated thyroid carcinoma previously submitted to total thyroidectomy. False-positive whole-body scans may occur due to misinterpretation of the physiologic distribution of the radioisotope or lack of knowledge on the existence of other pathologies that could eventually present radioiodine uptake. Thymic uptake is an uncommon cause of false-positive whole-body scan, and the mechanism through which it occurs is not completely understood. The present paper reports five cases of patients with differentiated thyroid cancer who presented a mediastinum uptake of radioiodine in a whole-body scan during follow-up. The patients had either histological or radiological confirmation of the presence of residual thymus gland. It is very important to know about the possibility of iodine uptake by the thymus in order to avoid unnecessary treatment, such as surgery or radioiodine therapy. (author)

  6. The Hypothalamic-Pituitary-Thyroid Axis in Infants and Children: Protection from Radioiodines

    Directory of Open Access Journals (Sweden)

    Jeffrey Fisher


    Full Text Available Potassium iodide (KI is recommended as an emergency treatment for exposure to radioiodines, most commonly associated with nuclear detonation or mishaps at nuclear power plants. Protecting the thyroid gland of infants and children remains a priority because of increased incidence of thyroid cancer in the young exposed to radioiodines (such as 131I and 133I. There is a lack of clinical studies for KI and radioiodines in children or infants to draw definitive conclusions about the effectiveness and safety of KI administration in the young. In this paper, we compare functional aspects of the hypothalamic-pituitary-thyroid (HPT axis in the young and adults and review the limited studies of KI in children. The HPT axis in the infant and child is hyperactive and therefore will respond less effectively to KI treatment compared to adults. Research on the safety and efficacy of KI in infants and children is needed.

  7. Radioiodine therapy increases the risk of cerebrovascular events in hyperthyroid and euthyroid patients

    DEFF Research Database (Denmark)

    la Cour, Jeppe Lerche; Jensen, Lars Thorbjoern; Vej-Hansen, Anders


    BACKGROUND AND OBJECTIVE: Hyperthyroid patients treated with radioiodine have increased morbidity and mortality from cerebrovascular events. This risk has until now has been attributed to the hyperthyroidism. However, radioiodine therapy of benign thyroid diseases exposes the carotid arteries...... to radiation and is capable of inducing atherosclerosis. The objective of the study was to elucidate whether ionizing radiation from radioiodine might contribute to cerebrovascular morbidity. METHODS: In a retrospective register cohort study, 4000 hyperthyroid and 1022 euthyroid goitre patients treated...... of cerebrovascular events among all treated patients, hazard ratio (HR) 1.18 (95% CI 1.09-1.29). The risk was increased among hyperthyroid (HR 1.17; 95% CI 1.07-1.28) as well as euthyroid patients (HR 1.21; 95% CI 1.02-1.44). CONCLUSIONS: We report an increased risk of cerebrovascular events in hyperthyroid as well...

  8. Procedure guideline for radioiodine test (version 3); Verfahrensanweisung zum Radioiodtest (Version 3)

    Energy Technology Data Exchange (ETDEWEB)

    Dietlein, M.; Schicha, H. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Koeln Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Dressler, J. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Nuklearmedizinische Klinik der Henriettenstiftung, Hannover (Germany); Eschner, W. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Deutsche Gesellschaft fuer Medizinische Physik (DGMP) (Germany); Koeln Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Lassmann, M. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Deutsche Gesellschaft fuer Medizinische Physik (DGMP) (Germany); Wuerzburg Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Leisner, B. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Allgemeines Krankenhaus St. Georg, Hamburg (Germany). Abt. fuer Nuklearmedizin; Reiners, C. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Wuerzburg Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin


    The version 3 of the procedure guideline for radioiodine test is an update of the guideline previously published in 2003. The procedure guideline discusses the pros and cons of a single measurement or of repeated measurements of the iodine-131 uptake and their optimal timing. Different formulas are described when one, two or three values of the radioiodine kinetic are available. The probe with a sodium-iodine crystal, alternatively or additionally the gamma camera using the ROI-technique are instrumentations for the measurement of iodine-131 uptake. A possible source of error is an inappropriate measurement (sonography) of the target volume. The patients' preparation includes the withdrawal of antithyroid drugs 2-3 days before radioiodine administration. The patient has to avoid iodine-containing medication and the possibility of additives of iodine in vitamin- and electrolyte-supplementation has to be considered. (orig.)

  9. Outcome of radioiodine therapy without, on or 3 days off carbimazole: a prospective interventional three-group comparison

    Energy Technology Data Exchange (ETDEWEB)

    Walter, Martin A. [University Hospital, Institute of Nuclear Medicine, Basel (Switzerland); University Hospital Basel, Division of Endocrinology, Diabetology and Clinical Nutrition, Basel (Switzerland); Christ-Crain, Mirjam; Mueller, Beat [University Hospital Basel, Division of Endocrinology, Diabetology and Clinical Nutrition, Basel (Switzerland); Schindler, Christian [University Hospital Basel, Institute of Social and Preventive Medicine, Basel (Switzerland); Mueller-Brand, Jan [University Hospital, Institute of Nuclear Medicine, Basel (Switzerland)


    Carbimazole ameliorates hyperthyroidism but reduces radioiodine uptake and adversely affects the outcome of simultaneous radioiodine therapy. We explored whether withdrawal of carbimazole for 3 days can restore the outcome of radioiodine treatment without concurrent exacerbation of hyperthyroidism. By generating three groups with comparable radioiodine uptake, we also investigated whether the effect of carbimazole depends on the radioiodine uptake. Stratified by a radioiodine uptake >30%, 227 consecutive adult patients were prospectively assigned to radioiodine therapy (target dose 200 Gy) without, on or 3 days off carbimazole. Patients were clinically (Crooks-Wayne score) and biochemically (T{sub 3}, fT{sub 4}, TSH) followed up after 3, 6 and 12 months. Primary endpoint was outcome 12 months after radioiodine therapy. A total of 207 patients completed follow-up (toxic nodular goitre, n=117; Graves' disease, n=90). The overall success rate was 71.5%. Patients without and 3 days off carbimazole had similar biochemical (81.4% and 83.3%, respectively; p=0.82) and clinical outcomes [median (range) Crooks-Wayne score 0 (0-16) and 1 (0-10), respectively; p=0.73], which were both higher than in patients on carbimazole [42.6%, p<0.001; Crooks-Wayne score 3 (0-30), p<0.03]. Time to achieve cure was delayed on carbimazole. No changes in thyroid hormone levels occurred after 3 days' discontinuation of carbimazole. Logistic regression revealed that all observed cure rates were independent of entity, sex, age, thyroid volume, radioiodine uptake, radioiodine half-life, fT{sub 4}, T{sub 3} and TSH. (orig.)

  10. Evaluation of usefulness of radio-iodine SPECT/CT in differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Won; Lee, Ho Young; Oh, So Won; Kim, Seok Ki; Jeong, Ki Wook; Kim, Seon Wook; Kang, Keon Wook [National Cancer Center, Goyang (Korea, Republic of)


    Localizing and differentiating a metastatic lesion of differentiated thyroid cancer (DTC) by using radio iodine whole body scan could be difficult because a whole body scan (WBS) lacks anatomic information. This study was performed to evaluate the usefulness of radio-iodine SPECT/CT for differentiating equivocal lesions. Among 253 patients with DTC who had undergone radio-iodine scan between February and July 2006, 26 patients were enrolled (M:F = 8:18, Age 50.7 {+-} 12.5 years) in the study. The patients had abnormal uptakes in the WBSs that necessitated precise anatomical localization of differentiating between a metastatic lesion and a false-positive lesion. SPECT/CT was performed for the region with abnormal uptake in the WBS. WBS and SPECT/CT were evaluated visually. Metastases were diagnosed based on the results of the radio-iodine scan along with the results of other radiological examinations and serological tests. Based on the WBS images, 13 were suspected with cervical lymph mode (LN) metastases in 16 patients with abnormal neck uptake, and in the 11 patients with abnormal extra-cervical uptakes, extra-cervical metastases were doubtful in all. After SPECT/CT was performed, the diagnostic results were altered for 16 patients (62%). SPECT/CT revealed that only 5 patients had cervical LN metastases, while 3 patients had extra-cervical (mediastinal) LN metastases. Overall there was a 58% (15/26) change in diagnoses and plans for treatment due to SPECT/CT. Among 8 patients suspected with metastases on SPECT/CT, 6 patients underwent another radio-iodine therapy. In 96% (24/25) of the patients, the results of SPECT/CT corresponded with those of further radiological examinations and with other clinical information. Radio-iodine SPECT/CT images permitted the differentiation of abnormal radio-iodine uptake and improved anatomical interpretation in DTC.

  11. Radioiodine therapy in patients with type II amiodarone-induced thyrotoxicosis. (United States)

    Czarnywojtek, Agata; Warmuz-Stangierska, Izabela; Woliński, Kosma; Płazińska, Maria; Kobylecka, Małgorzata; Kunikowska, Jolanta; Stangierski, Adam; Miechowicz, Izabela; Waligórska-Stachura, Joanna; Rewers, Amanda; Królicki, Leszek; Ruchała, Marek


    The treatment of amiodarone-induced thyrotoxicosis (AIT) still remains a clinical challenge, requiring the cooperation of both endocrinologists and cardiologists. Unfortunately, even today AIT is related to significantly increased mortality. The aim of this study was to compare the efficacy of radioidine therapy for type II AIT in 2 groups of patients: with high or normal radioiodine uptake and treated by amiodarone (AM) in the past (AM- group) and with low radioiodine uptake and currently treated with AM (AM+ group). The AM- group included 57 patients and the AM+ group, 49. All patients received iodine-131 at a dose of 22mCi~800. Patient data were collected for over 2 years. After radioiodine administration, serum thyroid-stimulating hormone levels in the AM- group and AM+ group were 0.0 ±0.0 and 0.0 ±0.0, respectively, at 1 month; 1.2 ±3.3 and 0.6 ±1.2, respectively, at 12 months; and 4.2 ±3.6 and 1.9 ±0.8, respectively, at 2 years. All differences between the groups were statistically significant (P death occurred in 22 patients in the AM+ group and 6 patients in the AM- group. Radioiodine treatment is a safe and effective therapeutic modality for patients with type II AIT despite low radioiodine uptake, especially for patients with contraindications to other types of treatment (eg, thyroidectomy). Moreover, since thyrotoxicosis in patients with AIT is a significant risk factor for increased mortality, and since there are no alternative antiarrythmic treatments, radioiodine administration seems to be the only effective therapeutic modality.

  12. Radioiodine treatment of recurrent hyperthyroidism in patients previously treated for Graves' disease by subtotal thyroidectomy

    DEFF Research Database (Denmark)

    Vestergaard, H; Laurberg, P


    Radioiodine therapy is often employed for treatment of patients with relapse of hyperthyroidism due to Graves' disease, after previous thyroid surgery. Little is known about the outcome of this treatment compared to patients with no previous surgery. A total of 20 patients who had received surgical...... treatment for Graves' hyperthyroidism 1-46 years previously and with relapse of the hyperthyroidism, and 25 patients with hyperthyroidism due to Graves' disease and no previous thyroid surgery were treated with radioiodine, following the same protocol. Early after treatment the previously operated patients...

  13. Effectiveness of Radioiodine Treatment for Toxic Nodular Goiter

    Directory of Open Access Journals (Sweden)

    Hatice Şakı


    Full Text Available Objective: The aim of this retrospective study is to evaluate the treatment outcomes in patients with toxic nodular goiter (TNG that received radioiodine treatment (RAIT and to determine the influence of age, gender, nodule size, I-131 dose, underlying etiology and antithyroid drugs on the outcomes of RAIT. Methods: Two hundred thirty three patients (mean 64±10 years old with TNG that received RAIT were included in the study. Treatment success was analyzed according to demographic (age and gender and clinical data (thyroid function tests before and after RAIT, thyroid sonography and scintigraphy, I-131 dose, antithyroid drugs. A fixed dose of 555 MBq was administered to patients with nodules smaller than 2 cm in diameter and of 740 MBq to patients with nodules larger than 2 cm. Hyperthyroidism treatment success was defined as achieving hypothyroidism or euthyroidism six months after RAIT. Results: In our study, the cure rate was 93.9% six months after RAIT. Hypothyroidism was observed in 74 (31.7% patients, and euthyroidism was achieved in 145 (62.2% patients while 14 (6% patients remained in hyperthyroid state. Age and gender did not affect treatment outcomes. No correlation was found between underlying etiology or antithyroid drugs and therapeutic effectiveness. The effectiveness of RAIT was better in patients with nodules smaller than 2 cm. Conclusion: We observed that high cure rates were obtained in patients with TNG with 555 MBq and 740 MBq doses of I-131. While nodule diameter and RAI dose are important factors for treatment efficacy; age, gender, underlying etiology and antithyroid drugs do not affect the outcome of RAIT.

  14. Embolization in combination with radioiodine therapy for bone metastases from differentiated thyroid carcinoma

    NARCIS (Netherlands)

    van Tol, KM; Hew, JM; Jager, PL; Vermey, A; Dullaart, RPF; Links, TP

    BACKGROUND The outcome for patients with bone metastases from differentiated thyroid carcinoma is worse compared to the overall prognosis of patients with differentiated thyroid carcinoma. The aim of this study is to evaluate the effect of embolization with concomitant radioiodine treatment on the

  15. A 30-year perspective on radioiodine therapy of benign nontoxic multinodular goiter

    DEFF Research Database (Denmark)

    Bonnema, Steen J; Hegedüs, Laszlo


    rate of permanent hypothyroidism, whereas other side-effects are very modest when using a rhTSH dose of 0.1 mg or below. SUMMARY: RhTSH-stimulated radioiodine therapy of benign nontoxic multinodular goiter is still an off-label use but several trials have shown that this treatment is significantly more...

  16. Improved radioiodination of 1,2-dipalmitoyl-3-IPPA via a tributyltin intermediate. (United States)

    McPherson, D W; Luo, H; Kropp, J; Knapp, F F


    1,2-Palmitoyl-3-[15-(4-iodophenyl)pentadecan-3-oyl]-rac-glycerol (MIPAG) is a new agent for the clinical evaluation of pancreatic lipase activity and has demonstrated promise in preliminary clinical studies with patients affected with pancreatic insufficiency. Iodine-131-MIPAG was initially prepared via thallium-iodide displacement. Because of the need for a simple method which is amendable for the routine clinical use of MIPAG we have investigated the preparation and radioiodination of MIPAG utilizing the tributyltin precursor, 1,2-palmitoyl-3-[15-(4-tributylstannylphenyl)pentadecan-3-oy l]-rac-glycerol (TBT-MIPAG, 2). Compound 2 was prepared via the condensation of 1,2-palmitoyl-rac-glycerol with 15-(4-tributylstannylphenyl)pentadecanoic acid (TBT-PPA) prepared from 4-bromophenylacetylene. Electrophilic radioiodination using peracetic acid with sodium iodide-125 in ethanol at 80 degrees C for 60 min afforded I-125-MIPAG in 65.9% (+/- 11.5%) yield and radiochemical purity of 94% (+/- 3.0%) after C-18 Sep-Pak purification (n = 6). This improved method for radioiodination utilizing TBT-MIPAG now provides radioiodinated MIPAG for routine clinical evaluation.

  17. Facile-radioiododemetallation reactions for the convenient preparation of radioiodinated compounds

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, P.C.; Knapp, F.F. Jr.; Kabalka, G.W.; Kunda, S.A.


    Several new methods for the preparation of vinyl iodides via mercuration and thallation reactions of vinylboronic acids have been explored. Chloramine-T oxidation of alkylvinylmercury iodides or iodide treatment of alkylvinylthallium trifluoroacetate substrates, prepared from the corresponding alkylvinylboronic acid and thallic trifluoroacetate, yields the corresponding alkylvinyl iodides. These methods are also efficient for the synthesis of the corresponding radioiodinated compounds. 21 references.


    Energy Technology Data Exchange (ETDEWEB)

    Workman, James B.


    Experience from the management of 156 patients with proven thyroid cancer, followed from 1 to 11 years, is reported. Although no sweeping conclusions can be drawn, it appears that radioiodine continues to have a place in the overall management of most cases of this malignant disease. (auth)

  19. Nationwide trends in surgery and radioiodine treatment for benign thyroid disease during iodization of salt

    DEFF Research Database (Denmark)

    Cerqueira, C.; Knudsen, N.; Ovesen, L.


    Objective: Iodization of salt was introduced in Denmark in 1998 because of mild-to-moderate iodine deficiency (ID). The aim of this study was to analyze the utilization rate of surgery and radioiodine therapy for benign thyroid disorders before and after the introduction of iodization, and to stu...

  20. Acute effects of radioiodine therapy on the voice and larynx of basedow-Graves patients

    Energy Technology Data Exchange (ETDEWEB)

    Isolan-Cury, Roberta Werlang; Cury, Adriano Namo [Sao Paulo Santa Casa de Misericordia, SP (Brazil). Medical Science School (FCMSCSP); Monte, Osmar [Sao Paulo Santa Casa de Misericordia, SP (Brazil). Physiology Department; Silva, Marta Assumpcao de Andrada e [Sao Paulo Santa Casa de Misericordia, SP (Brazil). Medical Science School (FCMSCSP). Speech Therapy School; Duprat, Andre [Sao Paulo Santa Casa de Misericordia, SP (Brazil). Medical Science School (FCMSCSP). Otorhinolaryngology Department; Marone, Marilia [Nuclimagem - Irmanity of the Sao Paulo Santa Casa de Misericordia, SP (Brazil). Nuclear Medicine Unit; Almeida, Renata de; Iglesias, Alexandre [Sao Paulo Santa Casa de Misericordia, SP (Brazil). Medical Science School (FCMSCSP). Otorhinolaryngology Department. Endocrinology and Metabology Unit


    Graves's disease is the most common cause of hyperthyroidism. There are three current therapeutic options: anti-thyroid medication, surgery, and radioactive iodine (I 131). There are few data in the literature regarding the effects of radioiodine therapy on the larynx and voice. The aim of this study was: to assess the effect of radioiodine therapy on the voice of Basedow-Graves patients. Material and method: A prospective study was done. Following the diagnosis of Grave's disease, patients underwent investigation of their voice, measurement of maximum phonatory time (/a/) and the s/z ratio, fundamental frequency analysis (Praat software), laryngoscopy and (perceptive-auditory) analysis in three different conditions: pre-treatment, 4 days, and 20 days post-radioiodine therapy. Conditions are based on the inflammatory pattern of thyroid tissue (Jones et al. 1999). Results: No statistically significant differences were found in voice characteristics in these three conditions. Conclusion: Radioiodine therapy does not affect voice quality. (author)

  1. Improved radioiodination of 1,2-dipalmitoyl-3-IPPA via a tributyltin intermediate

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, D.W. E-mail:; Luo, H.; Kropp, J.; Knapp, F.F


    1,2-Palmitoyl-3-[15-(4-iodophenyl)pentadecan-3-oyl]-rac-glyceroI (MIPAG) is a new agent for the clinical evaluation of pancreatic lipase activity and has demonstrated promise in preliminary clinical studies with patients affected with pancreatic insufficiency. Iodine-131-MIPAG was initially prepared via thallium-iodide displacement. Because of the need for a simple method which is amendable for the routine clinical use of MIPAG we have investigated the preparation and radioiodination of MIPAG utilizing the tributyltin precursor, 1,2-palmitoyl-3-[15-(-4-tributylstannylphenyl)pentadecan-3-oyl] -rac-glyceroI (TBT-MIPAG, 2). Compound 2 was prepared via the condensation of 1,2-palmitoyl-rac-glycerol with 15-(4-tributylstannylphenyl)pentadecanoic acid (TBT-PPA) prepared from 4-bromophenylacetylene. Electrophilic radioiodination using peracetic acid with sodium iodide-125 in ethanol at 80 deg. C for 60 min afforded I-125-MIPAG in 65.9% ({+-}11.5%) yield and radiochemical purity of 94% ({+-}3.0%) after C-18 Sep-Pak purification (n=6). This improved method for radioiodination utilizing TBT-MIPAG now provides radioiodinated MIPAG for routine clinical evaluation.

  2. Focal Bronchiectasis Causing Abnormal Pulmonary Radioiodine Uptake in a Patient with Well-Differentiated Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Ash Gargya


    Full Text Available Background. False-positive pulmonary radioactive iodine uptake in the followup of differentiated thyroid carcinoma has been reported in patients with certain respiratory conditions. Patient Findings. We describe a case of well-differentiated papillary thyroid carcinoma treated by total thyroidectomy and radioiodine ablation therapy. Postablation radioiodine whole body scan and subsequent diagnostic radioiodine whole body scans have shown persistent uptake in the left hemithorax despite an undetectable stimulated serum thyroglobulin in the absence of interfering thyroglobulin antibodies. Contrast-enhanced chest computed tomography has confirmed that the abnormal pulmonary radioiodine uptake correlates with focal bronchiectasis. Summary. Bronchiectasis can cause abnormal chest radioactive iodine uptake in the followup of differentiated thyroid carcinoma. Conclusions. Recognition of potential false-positive chest radioactive iodine uptake, simulating pulmonary metastases, is needed to avoid unnecessary exposure to further radiation from repeated therapeutic doses of radioactive iodine.

  3. Randomized prospective study comparing a single radioiodine dose and a single laser therapy session in autonomously functioning thyroid nodules

    DEFF Research Database (Denmark)

    Døssing, Helle; Bennedbaek, Finn Noe; Bonnema, Steen Joop


    OBJECTIVE: To compare the efficacy of interstitial laser photocoagulation (ILP) with radioiodine in hot thyroid nodules. DESIGN: Thirty consecutive outpatients with subclinical or mild hyperthyroidism and a scintigraphically solitary hot nodule with extraglandular suppression were randomized to e...

  4. Dosimetry in radioiodine therapy of benign thyroid diseases. Background and practice; Dosimetrie bei Radioiodtherapie benigner Schilddruesenerkrankungen. Hintergrund und Durchfuehrung

    Energy Technology Data Exchange (ETDEWEB)

    Bockisch, A.; Sonnenschein, W.; Jentzen, W.; Hartung, V.; Goerges, R. [Universitaetsklinikum Essen (Germany). Klinik fuer Nuklearmedizin


    Radioiodine therapy of benign thyroid diseases (focal = [toxic adenoma], multifocal, disseminated autonomy, Grave's disease or clinical relevant goitre) needs to be and can be performed individually for each patient. Most frequently a radioiodine test is performed applying a small activity of iodine-131 ({sup 131}I). The paper discusses some protocols for pre- or posttherapeutic dosimetry and discusses their advantages and disadvantages. All are based on the volumetry of the target tissue as well as the radioiodine kinetics in the target volume what may be represented by maximum uptake and half life of iodine retention in the thyroid. Possible disturbances and measuring uncertainties of these parameters are presented and discussed. In spite of the discussed uncertainties in dosimetry, due to its high therapeutic width radioiodine therapy is a very successful procedure to cure hyperthyroidism or to reduce goitre volume with only little side effects. (orig.)

  5. Glucocorticoid administration for Graves' hyperthyroidism treated by radioiodine. A questionnaire survey among members of the European Thyroid Association

    NARCIS (Netherlands)

    Lazarus, J. H.; Bartalena, L.; Marcocci, C.; Kahaly, G. J.; Krassas, G.; Wiersinga, W. M.; Baldeschi, L.; Boboridis, K.; Boschi, A.; Currò, N.; Daumerie, C.; Dickinson, A. J.; Eckstein, A.; Kendall-Taylor, P.; Lane, C. M.; Ludgate, M. E.; Mann, K.; Marinò, M.; Mourits, M. P.; Nardi, M.; Neoh, C.; Orgiazzi, J.; Pearce, S.; Perros, P.; Pinchera, A.; Pitz, S.; Salvi, M.; Sivelli, P.; Stahl, M.; von Arx, G.


    Background: Glucocorticoid prophylaxis is required in some instances after radioiodine (RAI) treatment for Graves' hyperthyroidism to prevent progression of Graves' orbitopathy (GO). However, no randomized clinical trial has been performed to ascertain the optimum glucocorticoid therapy. Aim and

  6. Radioiodinated PHIPA`s; metabolically trapped fatty acids

    Energy Technology Data Exchange (ETDEWEB)

    Eisenhut, M. [Heidelberg Univ. (Germany). Radiopharmaceutical Chemistry Lab.


    Radioiodinated PHIPA 3-10 [13-(4`-iodophenyl)-3-(p-phenylene)tridecanoic acid] has been developed for nuclear-cardiological investigation of coronary artery disease or cardiomyopathies of various origin. The compound features a phenylene group located within the backbone of a long-chain fatty acid. In spite of its bulky structure [{sup 123}I]PHIPA 3-10 is extracted by the myocardium in a manner similar to that for the unmodified fatty acid analogue, [{sup 123}I]IPPA. The retention of PHIPA 3-10 in heart muscle results from the presence of the p-phenylene group which prevents more than one {beta}-oxidation cycle. Only one single, rapidly formed metabolite was found in rat-heart extracts. According to comparative HPLC with synthetic metabolites and mass spectrometric analysis this metabolite was identified as [{sup 123}I]PHIPA 1-10, a by two methylene groups shortened PHIPA derivative. Formation of this metabolite could be suppressed by Etomoxir, a carnitine palmitoyl fransferase I inhibitor, indicating {beta}-oxidation of [{sup 123}I]PHIPA 3-10 in mitochondria. Final evidence for the involvement of mitochondria in the degradation of [{sup 123}I]PHIPA 3-10 was obtained performing density-gradient centrifugation with homogenized rat heart tissue. Labeled free PHIPA 3-10 and free metabolite peaked with the fraction containing mitochondria. With respect to its biochemical characteristics, [{sup 123}I]PHIPA 3-10 may be considered as a useful tool for nuclear cardiological investigations. (orig.) [Deutsch] Radioiodierte PHIPA 3-10 [13-(4`-Iodophenyl)-3-(p-phenylene)tridecanoic acid] wurde fuer Untersuchungen von koronaren Herzerkrankungen und Kardiomyopathien unterschiedlicher Genese entwickelt. Die Verbindung enthaelt eine in der Fettsaeurekette lokalisierte Phenylengruppe. Obwohl dieses Strukturelement raumfordernd ist, wird [{sup 123}I]PHIPA 3-10 aehnlich gut vom Herzmuskel aufgenommen, wie die unmodifizierte Fettsaeure [{sup 123}I]IPPA. Die auffallende

  7. Concurrent diseases in hyperthyroid cats undergoing assessment prior to radioiodine treatment. (United States)

    Puig, Jordi; Cattin, Isabelle; Seth, Mayank


    Hyperthyroidism is a common endocrinopathy of geriatric cats, which are also prone to various other diseases. This retrospective study examined the prevalence and type of non-renal concurrent diseases present in cats referred for radioiodine assessment that were believed to have no other comorbidities at the time of referral. Ninety-four cats were included and analysed. Seventeen cases (18%) were identified as having concurrent disorders, with alimentary lymphoma (n = 5) and chronic enteropathy (n = 4) as the two most common comorbid diseases. The eosinophil count, total bilirubin and total calcium were significantly higher in the concurrent disease group, although the differences are unlikely to be clinically useful. The results support the utility of careful and individual assessment for all hyperthyroid cats prior to receiving radioiodine. © ISFM and AAFP 2014.

  8. Radioiodination and biological evaluation of candesartan as a tracer for cardiovascular disorder detection. (United States)

    Sanad, M H; Sallam, Kh M; Marzook, F A; Abd-Elhaliem, S M


    The goal of the study aims to evaluate newly radioiodinated candesartan (CAN) as a potential cardiovascular tracer. CAN was labeled using 125 I with chloramine-T (Ch-T) and N-bromosuccinimide (NBS) with full characterization of cold Iodo-candesartan. Factors such as pH, reaction temperature, reaction time, substrate, and oxidizing agent amounts were studied to optimize the radioiodination of CAN. The optimum radiochemical yield of 125 I-CAN was 98%. The labeled compound was separated and purified using high-pressure liquid chromatography. The biological distribution indicates the suitability of 125 I-CAN as a novel tracer to detect cardiovascular disorders. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Synthesis and preliminary biological evaluation of new radioiodinated MMP inhibitors for imaging MMP activity in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Kopka, Klaus E-mail:; Breyholz, Hans-Joerg; Wagner, Stefan; Law, Marilyn P.; Riemann, Burkhard; Schroeer, Sandra; Trub, Monika; Guilbert, Benedicte; Levkau, Bodo; Schober, Otmar; Schaefers, Michael


    Non-invasive measurement of matrix metalloproteinase (MMP) activity in vivo is a clinical challenge in many disease processes such as inflammation, tumor metastasis and atherosclerosis. Therefore, radioiodinated analogues of the non-peptidyl broad-spectrum MMP inhibitor (MMPI) CGS 27023A 1a were synthesized for non-invasive detection of MMP activity in vivo using single photon emission computed tomography (SPECT). The compounds Br-CGS 27023A 1b and HO-CGS 27023A 1d were synthesized from the amino acid D-valine and used as precursors for radioiodinated derivatives of CGS 27023A and their non-radioactive references I-CGS 27023A 1c and HO-I-CGS 27023A 1e. Radioiodination of the precursors with [{sup 123}I]NaI or [{sup 125}I]NaI produced the no-carrier-added MMP inhibitors [{sup 123}I]I-CGS 27023A 1f, [{sup 125}I]I-CGS 27023A 1g, HO-[{sup 123}I]I-CGS27023A 1h, and HO-[{sup 125}I]I-CGS 27023A 1i. In vitro studies showed that the non-radioactive analogues of the MMP inhibitors exhibited affinities against gelatinase A (MMP-2) and gelatinase B (MMP-9) in the nanomolar range, comparable to the parent compound CGS 27023A. In vivo biodistribution using HO-[{sup 125}I]I-CGS 27023A 1i in CL57 Bl6 mice showed rapid blood and plasma clearance and low retention in normal tissues. The preliminary biological evaluation warrant further studies of these radioiodinated MMP inhibitors as potential new radiotracers for imaging MMP activity in vivo.

  10. The Effect of High Dose Radioiodine Therapy on Formation of Radiation Retinopathy During Thyroid Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tülay Kaçar Güvel


    Full Text Available Objective: Non-thyroidal complication of high-dose radioiodine therapy for thyroid carcinoma might cause salivary and lacrimal gland dysfunction, which may be transient or permanent in a dose-dependent manner. However, radiation retinopathy complicating 131I therapy, has not been previously well characterized. The aim of this study was to evaluate the extent of retinal damage among patients who had received high doses of radioiodine treatment. Methods: Forty eyes of 20 patients (3 male, 17 female who received 250-1000 mCi during 131I therapy and on ophthalmological follow up for a year after the last treatment were included in the study. Mean age of the study group was 50 years (range 25-70 years. In ophthalmologic examination, visual acuity was measured in order to determine visual loss. Intraocular pressure was measured in all the patients. Then lens examination was carried out with slit lamp biomicroscopy in order to investigate cataract or partial lens opacities. Fundus observation was carried out through the dilated pupil with slit lamp biomicroscopy using 90 D noncontact lens. Result: The best corrected visual aquity with Snellen chart was found as 1.0 in 36 eyes (90% and between 0.6 and 0.9 (10% in 4 eyes (10%. At the biomicroscopic fundus examination, retinal hemorrhage consistent with radiation retinopathy, microaneurysm, microinfarction, edema or exudation, vitreus hemorrhage, partial or total optical disc pallor indicating papillopathy in the optic disc were not observed in any of the eyes. Conclusion: This result indicates that there is not any significant correlation between repeated high-dose radioiodine therapy and radiation retinopathy in differentiated thyroid carcinomas. Even though there is not a significant restriction in use of higher doses of radioiodine therapy in differentiated thyroid carcinoma, more extensive studies are needed in order to obtain more accurate data on possible occurrence of retinopathy.

  11. The effect of high dose radioiodine therapy on formation of radiation retinopathy during thyroid cancer treatment. (United States)

    Kaçar Güveli, Tülay; Özkan, Sezer; Öner Tamam, Müge; Uyanık, Ercan; Ediz, Nurcan; Mülazımoğlu, Mehmet; Özpaçacı, Tevfik


    Non-thyroidspan>al complication of high-dose radioiodine therapy for thyroid carcinoma might cause salivary and lacrimal gland dysfunction, which may be transient or permanent in a dose-dependent manner. However, radiation retinopathy complicating 131I therapy, has not been previously well characterized. The aim of this study was to evaluate the extent of retinal damage among patients who had received high doses of radioiodine treatment. Forty eyes of 20 patients (3 male, 17 female) who received 250-1000 mCi during 131I therapy and on ophthalmological follow up for a year after the last treatment were included in the study. Mean age of the study group was 50 years (range 25-70 years). In ophthalmologic examination, visual acuity was measured in order to determine visual loss. Intraocular pressure was measured in all the patients. Then lens examination was carried out with slit lamp biomicroscopy in order to investigate cataract or partial lens opacities. Fundus observation was carried out through the dilated pupil with slit lamp biomicroscopy using 90 D noncontact lens. The best corrected visual aquity with Snellen chart was found as 1.0 in 36 eyes (90%) and between 0.6 and 0.9 (10%) in 4 eyes (10%). At the biomicroscopic fundus examination, retinal hemorrhage consistent with radiation retinopathy, microaneurysm, microinfarction, edema or exudation, vitreus hemorrhage, partial or total optical disc pallor indicating papillopathy in the optic disc were not observed in any of the eyes. This result indicates that there is not any significant correlation between repeated high-dose radioiodine therapy and radiation retinopathy in differentiated thyroid carcinomas. Even though there is not a significant restriction in use of higher doses of radioiodine therapy in differentiated thyroid carcinoma, more extensive studies are needed in order to obtain more accurate data on possible occurrence of retinopathy.

  12. Radioiodine treatment of non-toxic multinodular goitre: effects of combination with lithium

    Energy Technology Data Exchange (ETDEWEB)

    Vannucchi, Guia; Mannavola, Deborah; Dazzi, Davide; Beck-Peccoz, Paolo; Fugazzola, Laura [Ospedale Maggiore IRCCS (Pad. Granelli), Institute of Endocrine Sciences, Milan (Italy); Chiti, Arturo; Rodari, Marcello; Tadayyon, Sara [Istituto Clinico Humanitas, Nuclear Medicine Unit, Milan (Italy)


    This study aimed to evaluate the effects of radioiodine ({sup 131}I), alone or in combination with lithium, on thyroid volume and the prevention of radioiodine-induced thyrotoxicosis. This is the first clinical trial including only patients with multinodular goitre, normal TSH values and negative anti-thyroid auto-antibodies at baseline. Eighty consecutive patients were randomised to receive {sup 131}I plus lithium (group I+L) or {sup 131}I alone (group I). Thyroid ultrasonography and biochemical analyses were performed at baseline and at 1, 3, 6, 12 and 24 months after treatment. At 1-4 weeks after treatment, {sup 131}I-induced hyperthyroidism was observed in 58.8% of patients and was prevented by lithium administration. A low incidence of hypothyroidism (19%) was recorded at 24 months, whereas up to 44% of patients developed anti-thyroid antibodies. A significant reduction in thyroid volume was observed after {sup 131}I, with a mean decrease of 47.2% (median 48.2%) at 24 months, without differences between the groups. Moreover, it was shown that the decrease in thyroid volume after {sup 131}I was also due to the significant shrinkage of thyroid nodules. This demonstrates that adjunctive lithium is able to reduce radioiodine-induced hyperthyroidism. Therefore, such treatment appears to be safe in older patients and those with underlying cardiovascular disease. In the present large series, {sup 131}I therapy was demonstrated to be highly effective in reducing thyroid and nodular volume even in patients treated with low {sup 131}I doses (2.5 MBq/ml of thyroid tissue), further supporting the view that radioiodine therapy represents a real alternative to surgery. (orig.)

  13. Childhood Thyroid Radioiodine Exposure and Subsequent Infertility in the Intermountain Fallout Cohort (United States)

    Stone, Mary Bishop; Lyon, Joseph L.; VanDerslice, James A.; Alder, Stephen C.


    Background: Above-ground and underground nuclear weapon detonation at the Nevada Test Site (1951–1992) has resulted in radioiodine exposure for nearby populations. Although the long-term effect of environmental radioiodine exposure on thyroid disease has been well studied, little is known regarding the effect of childhood radioiodine exposure on subsequent fertility. Objectives: We investigated early childhood thyroid radiation exposure from nuclear testing fallout (supplied predominantly by radioactive isotopes of iodine) and self-reported lifetime incidence of male or female infertility or sterility. Methods: Participants were members of the 1965 Intermountain Fallout Cohort, schoolchildren at the time of exposure who were reexamined during two subsequent study phases to collect dietary and reproductive histories. Thyroid radiation exposure was calculated via an updated dosimetry model. We used multivariable logistic regression with robust sandwich estimators to estimate odds ratios for infertility, adjusted for potential confounders and (in separate models) for a medically confirmed history of thyroid disease. Results: Of 1,389 participants with dosimetry and known fertility history, 274 were classified as infertile, including 30 classified as sterile. Childhood thyroid radiation dose was possibly associated with infertility [adjusted odds ratio (AOR) = 1.17; 95% CI: 0.82, 1.67 and AOR = 1.35; 95% CI: 0.96, 1.90 for the middle and upper tertiles vs. the first tertile of exposure, respectively]. The odds ratios were attenuated (AOR = 1.08; 95% CI: 0.75, 1.55 and AOR = 1.29; 95% CI: 0.91, 1.83 for the middle and upper tertiles, respectively) after adjusting for thyroid disease. There was no association of childhood radiation dose and sterility. Conclusion: Our findings suggest that childhood radioiodine exposure from nuclear testing may be related to subsequent adult infertility. Further research is required to confirm this. PMID:23099433

  14. Transfer factors of radioiodine from volcanic-ash soil (Andosol) to crops

    Energy Technology Data Exchange (ETDEWEB)

    Ban-Nai, Tadaaki; Muramatsu, Yasuyuki [National Inst. of Radiological Sciences, Chiba (Japan). Environmental and Toxicological Sciences Research Group


    In order to obtain soil-to-plant transfer factors (TFs) of radioiodine from volcanic-ash soil to agricultural crops, we carried out radiotracer experiments. The mean values of TFs (on a wet weight basis) of radioiodine from Andosol to edible parts of crops were as follows: water dropwort, 0.24; lettuce, 0.00098; onion, 0.0011; radish, 0.0044; turnip, 0.0013 and eggplant, 0.00010. The mean value of the TFs of radioiodine for edible parts of wheat (on a dry weight basis) was 0.00015. We also studied the distributions of iodine in crops. There was a tendency for the TFs of leaves to be higher than those of tubers, fruits and grains. A very high TF was found for water dropwort, because this plant was cultivated under a waterlogged condition, in which iodine desorbed from soil into soil solution with a drop in the Eh value. The data obtained in this study should be helpful to assess the long-lived {sup 129}I (half life: 1.57 x l0{sup 7} yr) pathway related to the fuel cycle. (author)

  15. Heart rate Variability and Efficiency Assessment of Graves' Disease Radioiodine Therapy

    Directory of Open Access Journals (Sweden)

    M L Budkina


    Full Text Available Time of the transformation to the euthyroid condition after radioiodine therapy of Grave’s disease is individual and deviates from weeks to months, what requires frequent hormones control. The aim of this study was the assessment of possibility to use HRV parameters in dynamic control after the radioiodine therapy. 77 patients were examined with 114 fT4 measurement and HRV parameters recording (before radioiodine administration and in 1, 3, 6, 12 months after. From HRV parameters two were chosen as characterizing the closest correlation with fT4 and relatively independent from each other. The whole sample was divided into the teaching set (86 measurements and the test set (28 measurements. The decision rule was found by support vector machine in the teaching set asf(HR,SDNN = 0.995 lg(HR – 0.104 lg(SDNN – 1.703, where f is the indicator of the thyroid gland function, HR – heart rate during 5-minute ECG recording; SDNN – standard deviation of RR intervals; 0.995 , 0.104 and 1.703 – correcting coefficients. If f > 0, the thyrotoxicosis takes place in a patient. If f < 0 – there is no thyrotoxicosis. The analysis of diagnostic method precision in testing set gave the following results: diagnostic sensitivity was 71%, the diagnostic specificity 79%. This method can predict thyrotoxicosis elimination or relapse with high possibility. Its use can optimize thyroid function control and refuse from fixed time hormone measurement.

  16. Stereoselective synthesis of an iodinated resveratrol analog: Preliminary bioevaluation studies of the radioiodinated species

    Energy Technology Data Exchange (ETDEWEB)

    Dhyani, Manish V.; Kameswaran, Mythili; Korde, Aruna G.; Pandey, Usha [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Chattopadhyay, Subrata [Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Banerjee, Sharmila, E-mail: [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)


    Stereoselective synthesis of an E-hydroxystilbene has been carried out using the McMurry reaction. Synthesis of a monoiodinated hydroxystilbene has been carried out by a McMurry cross-coupling reaction. For the purpose of biological evaluation, the facile electrophilic substitution route has been attempted to radioiodinate it with {sup 125}I. The HPLC pattern of the radioiodinated hydroxystilbene, which could be obtained in >90% radiochemical purity, was found to be identical to that of its non-radioactive analog that has been independently prepared using the McMurry cross-coupling route. In vitro cell uptake studies were carried out in breast cancer cells MCF7, overexpressing estrogen receptors. In vivo biodistribution studies in female Swiss mice show a uterine uptake of 0.85{+-}0.4% ID/g at 3 h.p.i. with a uterus to muscle ratio of 2.83. Uptake in the thyroid was insignificant indicating good in vivo stability of the radioiodinated hydroxystilbene.

  17. Strategies of radioiodine ablation in patients with low-risk thyroid cancer. (United States)

    Schlumberger, Martin; Catargi, Bogdan; Borget, Isabelle; Deandreis, Désirée; Zerdoud, Slimane; Bridji, Boumédiène; Bardet, Stéphane; Leenhardt, Laurence; Bastie, Delphine; Schvartz, Claire; Vera, Pierre; Morel, Olivier; Benisvy, Danielle; Bournaud, Claire; Bonichon, Françoise; Dejax, Catherine; Toubert, Marie-Elisabeth; Leboulleux, Sophie; Ricard, Marcel; Benhamou, Ellen


    It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care. In our randomized, phase 3 trial, we compared two thyrotropin-stimulation methods (thyroid hormone withdrawal and use of recombinant human thyrotropin) and two radioiodine ((131)I) doses (i.e., administered activities) (1.1 GBq and 3.7 GBq) in a 2-by-2 design. Inclusion criteria were an age of 18 years or older; total thyroidectomy for differentiated thyroid carcinoma; tumor-node-metastasis (TNM) stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (with tumor diameter ≤1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage, or pT2N0; absence of distant metastasis; and no iodine contamination. Thyroid ablation was assessed 8 months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin-stimulated thyroglobulin. Comparisons were based on an equivalence framework. There were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the (131)I doses and between the thyrotropin-stimulation methods. The use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; number, NCT00435851; INCa number, RECF0447.).

  18. Persistent high TRAb values during pregnancy predict increased risk of neonatal hyperthyroidism following radioiodine therapy for refractory hyperthyroidism. (United States)

    Hamada, Noboru; Momotani, Naoko; Ishikawa, Naofumi; Yoshimura Noh, Jaeduk; Okamoto, Yasuyuki; Konishi, Toshiaki; Ito, Koichi; Ito, Kunihiko


    Serum levels of TSH receptor antibody (TRAb) often increase after radioiodine treatment for Graves' disease, and high-serum levels of maternal TRAb in late pregnancy indicate a risk of neonatal hyperthyroidism. The aim of this retrospective study is to investigate the characteristics of Graves' women who had a history of radioiodine treatment for intractable Graves' disease, and whose neonates suffered from hyperthyroidism. The subjects of this study were 45 patients with Graves' disease who became pregnant during the period from 1988 to 1998 after receiving radioiodine treatment at Ito Hospital. 25 of the 45 subjects had had a relapse of hyperthyroidism after surgical treatment for Graves' disease. 19 pregnancies were excluded because of artificial or spontaneous abortion. In the remaining 44 pregnancies of 35 patients, neonatal hyperthyroidism developed in 5 (11.3%) pregnancies of 4 patients. Serum levels of TRAb at delivery were higher in patients whose neonates suffered from hyperthyroidism (NH mother) than those of patients who delivered normal infants (N mother). Furthermore, serum levels of TRAb in NH mother did not change during pregnancy, although those of 4 patients of N mother, in which serum levels of TRAb before radioiodine treatment were as high as in NH mother, decreased significantly during pregnancy. In conclusion, women who delivered neonates with hyperthyroidism following radioiodine treatment seem to have very severe and intractable Graves' disease. Persistent high TRAb values during pregnancy observed in those patients may be a cause of neonatal hyperthyroidism.

  19. A prospective study of the effects of radioiodine therapy for hyperthyroidism in patients with minimally active graves' ophthalmopathy. (United States)

    Perros, Petros; Kendall-Taylor, Pat; Neoh, Chris; Frewin, Sarah; Dickinson, Jane


    Radioiodine is an effective and safe treatment for hyperthyroidism but has been implicated as a risk factor for deterioration or new presentation of Graves' ophthalmopathy (GO). Prophylactic glucocorticoids appear to prevent this effect. The objective of this study was to document the course of GO after radioiodine therapy. This was a prospective observational study. Patients were assessed at baseline and 2, 4, 6, and 12 months after radioiodine therapy. The study was conducted at a tertiary referral center. Seventy-two GO patients with minimally active eye disease participated in the study. A fixed dose of radioiodine was administered. T(4) was commenced 2 wk later to prevent hypothyroidism. Change in activity and severity of GO were analyzed. Exophthalmometer readings, the width of the palpebral aperture, diplopia scores, and the clinical activity score improved significantly. By clinically significant criteria, the eye disease improved in four patients (transiently in three of the four cases), most likely attributable to the natural course of the disease. No patient's eyes deteriorated. Radioiodine is not associated with deterioration of GO in patients with minimally active eye disease when postradioiodine hypothyroidism is prevented.

  20. Correlation of consecutive serum thyroglobulin levels during hormone withdrawal and failure of initial radioiodine ablation in thyroid cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hyuk Jin; Kim, Sung Hoon; O, Joo Hyun; Lee, Yeong Joo; Kim, Hyoung Woo [Dept. of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Seo, Ye Young [Dept. of Nuclear Medicine, College of Medicine, The Inje University Sanggye Paik Hospital, Seoul (Korea, Republic of); Ryu, Ji Young [Dept. of Radiology, Incheon St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)


    The aim of this study was to evaluate the value of thyroglobulin (Tg) kinetics during preparation of radioiodine ablation for prediction of initial radioiodine ablation failure in thyroid cancer patients. Thyroid cancer patients after total thyroidectomy who underwent radioiodine ablation with 3–4 weeks of hormone withdrawal between May 2011 and January 2012 were included. Consecutive serum Tg levels 5–10 days before ablation (Tg1) and on the day of ablation (Tg2) were obtained. The difference between Tg1 and Tg2 (ΔTg), daily change rate of Tg (ΔTg/day) and Tg doubling time (Tg-DT) were calculated. Success of initial ablation was determined by the results of the follow-up ultrasonography, diagnostic radioiodine scan and stimulated Tg level after 6 to 20 months. A total of 143 patients were included. Failed ablation was reported in 52 patients. Tg2 higher than 5.6 ng/ml and Tg-DT shorter than 4.2 days were significantly related to a high risk of ablation failure. ΔTg and ΔTg/day did not show significant correlation with ablation failure. Thyroglobulin kinetics on consecutive blood sampling during hormone withdrawal may be helpful in predicting patients with higher risk of treatment failure of initial radioiodine ablation therapy in thyroid cancer patients.

  1. Assessment of exposure of workers to ionizing radiation from radioiodine and technetium in nuclear medicine departmental facilities. (United States)

    Krajewska, Grazyna; Pachocki, Krzysztof A


    Due to its use of ionising radiation, the field of nuclear medicine is a unique and significant part of medical diagnostics and patient treatment. The aim of this study was to assess the internal exposure of nuclear medicine employees to radioiodine 131I and technetium 99mTc as well as to assess the external exposure doses. The radioiodine 131I and technetium 99mTc contents in the thyroid of staff members (about 100 persons) dealing with these radionuclides have been measured in four departments of nuclear medicine. The measurements were conducted with a portable detection unit for in situ measurements of radioiodine and technetium. High sensitivity environmental thermoluminescent dosimeters (TLD) were used to measure the external exposure dose. The average values and ranges of radioiodine 131I activity measured in the thyroids of all of the medical units' employees were: 83 Bq (range: 70-250 Bq), 280 Bq (range: 70-4000 Bq), 275 Bq (range: 70-1000 Bq) for technical staff, nuclear medicine staff and hospital services staff, respectively. The mean value of technetium 99mTc content in the thyroids of nuclear medicine staff was approximately 1500 Bq (range: 50--1800 Bq). External exposure dose rates were in the range of 0.5-10 microGy/h. The calculated average effective dose for particular person caused by the inhalation of radioiodine 131I is below 5% of 20 mSv/year (occupational exposure limit).

  2. Evaluation of cell cytotoxicity after ganciclovir treatment by radioiodinated IVDU

    Energy Technology Data Exchange (ETDEWEB)

    Lee, M. J.; Choi, T. H.; Woo, K. S. [Korean Institute of Radiological And Medical Sciences, Seoul (Korea, Republic of)] (and others)


    The herpes simplex virus type1 thymidine kinase(HSV1-tk) converts nontoxic nucleoside analogs such as ganciclovir into phosphorylated compounds that act as chain terminators and specially kill dividing cells. Unlike mammalian TK, HSV1-TK which is a nonspecific nucleoside kinase, is encoded by a viral gene that is not present in normal mammalian cells. Various radiolabelled nucleoside analogues are used as specific probes for HSV1-tk and can be freely transported across cell membranes. When phosphorylated by the tranduced HSV1-tk gene, the metabolites of probes subsequently accumulate within the transduced cells.

  3. Synthesis and Cellular Uptake of Radioiodine labeled 2{sup '}-deoxyuridine derivatives with HSV1-TK

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ah; Lee, Kyo Chul; Hong, Su Hee; Kim, Eun Jung; Lee, Jong Chan; An, Gwang Il; Choi, Tae Hyun; Cheon, Gi Jeong; Chun, Kwon Soo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)


    Several different radiolabeled probes have been developed to image Herpes Simplex Virus Type-1 thyrimidine kinase gene (HSV1-TK) expression. The nucleoside prodrugs under investigation for HSV1-TK imaging generally fall into two main chemical and radioisotope categories: the pyrimidine nucleosides, primarily radioiodinated, and the purin nucleosides, primarily radiofluorinated, and their respective analogues. In non-invasive imaging of the HSV1-TK system, many nucleoside derivatives have been recommended as HSV1-TK substrates. Most of these nucleoside derivatives have been developed as prodrugs for tumor proliferation imaging or as anti-viral drugs. For example, 5-fluorouracil (5-FU) and IUdR have been used as tumor agents and acyclovir (ACV), ganciclovir (GCV) and (E)-5-(2-bromovinyl)-2{sup '}- deoxyuridine (BVDU) as an anti-viral agents for virus infection several 5-substituted uracil nucleoside derivatives have been identified to have high sensitivity and selective accumulation in HSV1-TK expressing cells. Of those, IVDU was shown to be rapidly accumulated in HSV1- TK expressing cells in vitro. Imaging of the HSV1-TK reporter gene along with various reporter probes is of current interest. In contrast to the mammalian kinase, which phosphorylates thymidine preferentially, HSV1-TK is less discriminative and phosphorylates a wide range of nucleoside analogues such as acycloguanosines and 2{sup '}-fluoro-2{sup '}-deoxyuridine derivatives that are not phosphorylated efficiently by the native enzyme. More specifically, 5-substituted 2{sup '}-fluoro-2{sup '}-deoxyarabinofuranosyluracil nucleosides are efficiently phosphorylated by HSV- TK. This property, together with the presence of fluorine in the 2{sup '}-arabino-position, endows the 2{sup '}-fluoro-2{sup '}-deoxyuridines with antiviral activity against HSV.

  4. Radioiodinated O{sup 6}-Benzylguanine derivatives containing an azido function

    Energy Technology Data Exchange (ETDEWEB)

    Vaidyanathan, Ganesan, E-mail:; White, Benjamin; Affleck, Donna J.; McDougald, Darryl; Zalutsky, Michael R.


    Introduction: Drug resistance to alkylator chemotherapy has been primarily attributed to the DNA repair protein alkylguanine-DNA alkyltransferase (AGT); thus, personalizing chemotherapy could be facilitated if tumor AGT content could be quantified prior to administering chemotherapy. We have been investigating the use of radiolabeled O{sup 6}-benzylguanine (BG) analogues to label and quantify AGT in vivo. BG derivatives containing an azido function were sought to potentially enhance the targeting of these analogues to AGT, which is primarily present in the cell nucleus, either by conjugating them to nuclear localization sequence (NLS) peptides or by pretargeting via bio-orthogonal approaches. Methods: Two O{sup 6}-(3-iodobenzyl)guanine (IBG) derivatives containing an azido moiety-O{sup 6}-(4-azidohexyloxymethyl-3-iodobenzyl)guanine (AHOMIBG) and O{sup 6}-(4-azido-3-iodobenzyl)guanine (AIBG) - and their tin precursors were synthesized in multiple steps and the tin precursors were converted to radioiodinated AHOMIBG and AIBG, respectively. Both unlabeled and radioiodinated AHOMIBG analogues were conjugated to alkyne-derivatized NLS peptide heptynoyl-PK{sub 3}RKV. The ability of these radioiodinated compounds to bind to AGT was determined by a trichloroacetic acid precipitation assay and gel electrophoresis/phosphor imaging. Labeling of an AGT-AIBG conjugate via Staudinger ligation using the {sup 131}I-labeled phosphine ligand, 2-(diphenylphosphino)phenyl 4-[{sup 131}I]iodobenzoate, also was investigated. Results: [{sup 131}I]AHOMIBG was synthesized in two steps from its tin precursor in 52.2{+-}7.5% (n=5) radiochemical yield and conjugated to the NLS peptide via click reaction in 50.7{+-}4.9% (n=6) yield. The protected tin precursor of AIBG was radioiodinated in an average radiochemical yield of 69.6{+-}4.5% (n=7); deprotection of the intermediate gave [{sup 131}I]AIBG in 17.8{+-}4.2% (n=9) yield. While both [{sup 131}I]AHOMIBG and its NLS conjugate bound to AGT pure

  5. Interpretation of results of radioiodine measurements in thyroid for residents of Ukraine (1986). (United States)

    Likhtarov, I A; Kovgan, L M; Chepurny, M I; Masiuk, S V


    The purpose of this research is to make analysis, revision and estimation both reliability and accuracy of all measurements of radioiodine in the thyroid for residents of Ukraine, which were performed in 1986, and to justify the calibration factors to be applied for interpretation of measurements performed by non-calibrated devices. The radioiodine activity in the thyroid for residents of the most contaminated oblasts of Ukraine has been calculated on the base of 150 thousands direct measurements of the content of 131I in thyroid obtained in the frames of the thyroid monitoring in 1986. A method for the calculation of measurement errors has been developed and the accuracy of the errors has been determined assuming that the density of errors' distribution for main parameters of the measurements is close to Gaussian. Using the results of laboratory measurements, the calibration factors have been determined for integrated radiometers SRP-68-01 - devices which were often used to perform the thyroid dosimetric monitoring. The distribution of estimates on the content of radioiodine in thyroid is close to the lognormal one with geometric mean being equal to 4.8 kBq and geometric standard deviation being equal to 3.8. Most of these estimates (90 %) are in the range of 0.58-47 kBq, and the main set of their relative errors (90 %) are between 0.1 and 0.6. Thus, the model of thyroid activity observation with classical additive error has been obtained. I. A. Likhtarov, L. M. Kovgan, M. I. Chepurny, S. V. Masiuk.

  6. Salivary function after radioiodine therapy: poor correlation between symptoms and salivary scintigraphy

    Directory of Open Access Journals (Sweden)

    Jacqueline eJonklaas


    Full Text Available The aim of this study was to determine whether there was a correlation between salivary symptoms and salivary functioning following radioiodine therapy. Fifteen patients receiving radioactive iodine therapy for differentiated thyroid cancer completed a questionnaire assessing their salivary and nasal symptoms and underwent salivary scanning prior to therapy and 3 and 12 months after therapy. Measures of salivary gland accumulation and secretion were correlated with scores of salivary and nasal symptomatology. The mean number of salivary, nasal, and total symptoms at 3 months increased significantly over the number of symptoms at baseline by 3.7, 2.7, and 6.3 symptoms respectively (p values 0.001, 0.0046, and <0.001. The mean right parotid gland accumulation and secretion of radioisotope declined significantly at 3 months, compared with baseline. There was no association between the increase in salivary, nasal, or total symptoms and the change in scintigraphy measures. The increases in nasal and total symptoms were significant in those with co-existent Hashimoto’s disease, compared with those without this condition (p values 0.01 and 0.04. Nasal symptoms decreased (p value 0.04 in those who used sour candies, compared with those who did not. Increasing body mass index was significantly associated with increasing nasal symptoms (p value 0.05. Greater decline in salivary parameters at 3 months compared with baseline was generally associated with heavier body weight, decreased thyroid cancer stage, absence of Hashimoto’s thyroiditis, and pre-menopausal status. Although salivary and nasal symptoms increased and salivary scintigraphy parameters decreased after radioiodine therapy, the variables associated with symptoms and changes in salivary scan parameters differed. A better understanding of the relationship between salivary gland symptoms and functioning, and the factors affecting susceptibility to salivary and nasal damage after radioiodine

  7. Heath-related quality of life in thyroid cancer patients following radioiodine ablation

    Directory of Open Access Journals (Sweden)

    Henry Jean-françois


    Full Text Available Abstract Background There is limited information about the medium to long-term health-related quality of life (QOL in thyroid cancer patients after initial therapy and the existing studies suffer from limitations. The aim of the study was to assess the determinants of medium-term QOL after the initial therapy. Methods Following a total thyroidectomy, 88 thyroid cancer patients received either rhTSH or hypothyroid-assisted radioiodine ablation (RRA using 3.7 GBq (100 mCi of radioiodine. QOL evaluation of the patients using the validated Functional Assessment of Chronic Illness & Therapy (FACIT was performed at the time of inclusion (t0 and later at the 9-month post-RRA (t1. Results 83 patients were eligible for the final evaluation. Medium-term FACIT scores were not statistically different between t0 and t1 patients. All but one domain of the QOL score was similar between t0 and t1. Using a multivariate analysis, only age and immediate postoperative QOL scores were found to be determinants of the overall medium term 9-month QOL scores. Analysis showed that 'high QOL levels' (baseline and 9-month and 'no depression', 'low anxiety levels', were associated with ' Conclusions The use of radioiodine ablation does not seem to affect the medium term QOL scores of patients. Medium-term QOL is mainly determined by pre-ablation QOL. The assessment of baseline QOL might be interesting to evaluate in order to adapt the treatment protocols, the preventive strategies, and medical information to patients for potentially improving their outcomes.

  8. Pulmonary fibrosis in youth treated with radioiodine for juvenile thyroid cancer and lung metastases after Chernobyl

    Energy Technology Data Exchange (ETDEWEB)

    Hebestreit, Helge; Burkhardt, Antje [University Children' s Hospital, Wuerzburg (Germany); Biko, Johannes; Reiners, Christoph [University Hospital, Department of Nuclear Medicine, Wuerzburg (Germany); Drozd, Valentina [International Belarussian-German Foundation, Minsk (Belarus); Demidchik, Yuri [Thyroid Cancer Centre, Minsk (Belarus); Trusen, Andreas [Klinik fuer Radiologie, Johanniter-Krankenhaus, Genthin-Stendal gGmbH, Stendal (Germany); Beer, Meinrad [University Hospital, Department of Radiology, Wuerzburg (Germany)


    The objective of this project was to systematically determine the prevalence and consequences of pulmonary fibrosis in youth with thyroid carcinoma and lung metastases from Belarus who were treated with radioiodine ({sup 131}I). A total of 69 patients treated for juvenile thyroid carcinoma and lung metastasis with {sup 131}I were assessed. A group of 29 patients without lung metastases and prior {sup 131}I treatment served as controls. The assessments included a CT scan of the lungs, extensive pulmonary function testing and an incremental cycle test to volitional fatigue with measurements of oxygen uptake (V. O{sub 2}), oxygen saturation and alveolar-arterial difference in oxygen partial pressure ({delta}aaO{sub 2}). Five patients with lung metastases showed advanced pulmonary fibrosis on CT scans and also had poorer lung functions compared with the 62 patients with none or minor signs of fibrosis and the 29 controls. Furthermore, these five patients showed lower peak V.O{sub 2}, lower oxygen saturation at peak exercise and higher exercise {delta}aaO{sub 2}. They were younger at the time of cancer diagnosis and had received chemotherapy more frequently than youth with pulmonary metastases who did not develop fibrosis. One of the five patients subsequently died from pulmonary fibrosis. Following the Chernobyl catastrophe, about 7% of children treated with radioiodine for thyroid carcinoma and lung metastases displayed pulmonary fibrosis which was associated with functional impairments. Based on the characteristics of affected individuals, the number of radioiodine courses may have to be limited, especially in young children, and chemotherapy should be avoided. (orig.)

  9. Radioiodine treatment in McCune-Albright syndrome with hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Dhritiman Chakraborty


    Full Text Available McCune-Albright syndrome (MAS is a sporadic disease characterized by polyostotic fibrous dysplasia, "café-au-lait" spots and hyperfunctional endocrinopathies. Pathophysiological basis is activating mutation of the gene that encodes the alpha subunit of Gs membrane protein that stimulates the intracellular production of cAMP, conferring autonomous secretion of the gland in particular. One of the uncommon endocrine manifestations is hyperthyroidism. We present a patient who had café-au-lait spots, polyostotic fibrous dysplasia and hyperthyroidism. She was treated with radioactive iodine for the symptoms of hyperthyroidism and subsequently relieved from hyperthyroid features.

  10. Radioiodine therapy of benign non-toxic goitre. Potential role of recombinant human TSH

    DEFF Research Database (Denmark)

    Fast, S; Bonnema, S J; Hegedüs, L


    This review provides an update on recombinant human TSH (rh-TSH) augmented radioiodine (¹³¹I) therapy and outlines its potential role in the treatment of symptomatic benign multinodular non-toxic goitre. In some countries, ¹³¹I has been used for three decades to reduce the size of nodular goitres......-reduction (equality) strategy is attractive in terms of minimizing post-therapeutic restrictions and in reducing the potential risk of radiation-induced malignancy. Adverse effects like temporary thyroid swelling and thyroid hormone excess are to a large extent dose-dependent and generally 0.1mg rh-TSH or less...

  11. Radioiodine treatment of Grave's disease; Radiojodtherapie des Morbus Basedow

    Energy Technology Data Exchange (ETDEWEB)

    Heidenreich, P.; Vogt, H.; Dorn, R.; Graf, G.; Kopp, J. [Klinik fuer Nuklearmedizin, Zentralklinikum Augsburg (Germany)


    In Germany radioiodine therapy of Grave's disease is performed in patients older than 20 years, after at least one year of unsuccessful antithyroid therapy, intolerance against antithyroid medication, recurrences after surgical interventions and small goiters. Hyperthyroidism is eliminated with an ablative dose concept (300 Gy) in more than 90% associated with rate of hypothyroidism in the outcome of also more than 90%. Adverse prognostic factors are an insufficient dose to the thyroid and/or concomitant antithyreoid medication. Radioiodine therapy in Germany must be an inpatient single time approach due to quality assurance and radiation protection reasons. The mean hospitalization is only 3-4 days with the patient being discharged at an annual dose of less than 1 mSv at 2 m distance (dose rate at discharge < 3,5 {mu}Sv/h at 2 m). An adjuvant treatment with cortisone is recommended in a simultaneous endocrine ophthalmopathy to prevent from deterioration. Radioiodine therapy of Grave's disease is cost effective with a low probability of side-effects and is not associated with an increased genetic or somatic risk. Therapy control and life span follow up has to be carried out by the expert physician legally responsible for the radioiodine therapy. (orig.) [German] Die Radiojodtherapie des Morbus Basedow wird in Deutschland, bei Patienten aelter als 20 Jahre, erst nach mindestens einjaehriger, erfolgloser thyreostatischer Therapie, bei Thyreostatikaunvertraeglichkeit, Rezidiven nach Operation und kleinen Strumen durchgefuehrt. Die Beseitigung der Hyperthyreose wird mit einem ablativen Dosiskonzept (300 Gy) in > 90%, verbunden mit einer Hypothyreoserate von ebenfalls > 90% erreicht. Prognostisch unguenstige Einflussfaktoren sind eine zu niedrig gewaehlte Herddosis und/oder eine begleitende Thyreostase. Aus Gruenden der Qualitaetssicherung und des Strahlenschutzes muss in Deutschland die Radiojodtherapie stationaer als Einzeittherapie durchgefuehrt werden. Die

  12. Synthesis and preliminary pharmacological evaluation of a new putative radioiodinated AMPA receptor ligand for molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ross, T.L.; Sihver, W.; Ermert, J.; Coenen, H.H. [Forschungszentrum Juelich GmbH (Germany). Inst. fuer Neuroscience and Medicine (INM-5) - Nuclear Chemistry


    A new (radio)iodinated AMPA receptor ligand has been developed and pharmacologically evaluated in vitro and ex vivo using rodents. The new radioligand was directly labeled by electrophilic radioiodo-destannylation with iodine-131 in high radiochemical yields of 97% within 2 min. The new radioligand showed an excellent initial brain uptake of 2.1%ID/g at 10 min post injection, but a fast wash-out reduced the uptake by about 10-fold at 60 min post injection. Due to high nonspecific binding accompanied with a uniform distribution in brain tissue, however, the new radiotracer appears not suitable for AMPA receptor imaging in vivo.

  13. A randomized trial evaluating a block-replacement regimen during radioiodine therapy

    DEFF Research Database (Denmark)

    Bonnema, Steen J; Grupe, Peter; Boel-Jørgensen, Henrik


    Eur J Clin Invest 2010 ABSTRACT: Background  Lack of consensus regarding the antithyroid drug regimen in relation to radioiodine ((131) I) therapy of hyperthyroidism prompted this randomized trial comparing two strategies. Design  Patients with Graves' disease (GD, n = 51) or toxic nodular goitre...... (TNG, n = 49) were randomized to (131) I either 8 days following discontinuation of methimazole (-BRT, n = 52, median dose: 5 mg) or while on a continuous block-replacement regimen (+BRT, n = 48, median dose 15 mg methimazole and 100 μg levothyroxine). Results  Patients in the +BRT group required more...

  14. Investigation of a potential scintigraphic marker of apoptosis: radioiodinated Z-Val-Ala-DL-Asp(O-methyl)-fluoromethyl ketone

    Energy Technology Data Exchange (ETDEWEB)

    Haberkorn, Uwe E-mail:; Kinscherf, Ralf; Krammer, Peter H.; Mier, Walter; Eisenhut, Michael


    The imaging of apoptosis represents an attractive diagnostic goal in the area of tumor therapy, degenerative diseases and organ transplantation. Since caspases play a key role during the early period of the intracellular signal cascade of cells undergoing apoptosis we considered benzyloxycarbonyl-Val-Ala-DL-Asp(O-methyl)-fluoromethyl ketone [Z-VAD-fmk], a pan-caspase inhibitor, as a potential apoptosis imaging agent. Applying the Tl(TFA){sub 3}/[{sup 131}I]iodide method Z-VAD-fmk was successfully labeled at the benzyloxycarbonyl protecting group. The success of radioiodination, however, depended on the presence of carrier iodide resulting in specific radioactivities of 2.6 GBq/{mu}mol and the formation of a mixture of the 2- and 4-iodophenyl derivative (61%) which could not be separated by HPLC. Uptake measurements were performed with Morris hepatoma cells (MH3924Atk8) which showed expression of the Herpes Simplex Virus thymidine kinase (HSVtk) gene. Apoptosis was induced by treatment of the cells with 25 {mu}M ganciclovir. The TUNEL assay revealed 1.3{+-}0.3 and 23{+-}1.1% apoptotic cells immediately and 24 h after therapy, respectively. A two-fold increase of [{sup 131}I]IZ-VAD-fmk uptake was found at the end of treatment with the HSVtk/suicide system which constantly remained elevated for the following 4 hours. The slow cellular influx and lack of uptake saturation of [{sup 131}I]IZ-VAD-fmk are evidence for simple diffusion as transport mechanism. In addition, the absolute cellular uptake of [{sup 131}I]IZ-VAD-fmk was found to be low. This quality was related to the rather high lipophilicity of [{sup 131}I]IZ-VAD-fmk causing unspecific binding to macromolecules in the medium. Instead of using an inhibitor, synthetic caspase substrates are currently investigated which may accumulate in the apoptotic cell by metabolic trapping thereby enhancing the imaging signal.

  15. Subjective perception of radioactivity. No change post successful treatment with radioiodine; Strahlen bleiben boese. Keine Aenderung der subjektiven Konzepte von Radioaktivitaet nach erfolgreicher Radioiodtherapie

    Energy Technology Data Exchange (ETDEWEB)

    Freudenberg, L.S.; Mueller, S.P.; Beyer, T.; Bockisch, A. [Universitaetsklinikum Essen (Germany). Klinik fuer Nuklearmedizin


    We assess the attitude of patients with thyroid disease towards radiation and radioactivity before and after radioiodine therapy by means of a cultural-anthropological approach. We evaluate in patient interviews how their subjective attitude towards radioactivity as an abstract term and towards radioactivity in the medical context on the basis of their personal experiences with radionuclide therapy. 29 patients with autonomously functioning thyroid lesions (17 women, 12 men, 35-79 years) were included in this study. All patients were interviewed prior to and 22-27 month post radioiodine therapy in an open dialogue with the principal investigator. Patients were asked to describe their attitude towards radioactivity in general and towards radioiodine therapy in particular. Patients were asked to use a scoring system (1: positive, 5: negative) to quantify their perception of radioactivity. The personal perception of radioactivity as an abstract term does not change significantly (p = 0.15) before and after radioiodine therapy. This perception is linked to mostly negative impressions of radiactivity. However, patients become more positive when assessing the value of radioactivity as part of their therapy regimen. Thus, we observe a significant increase in percepted value of radioactivity post radioiodine therapy (p = 0.03). Patients continue to view radioactivity as something negative despite treatment success following radioiodine therapy. Our results provide useful information for patient information by the nuclear medicine physician prior to a radioiodine therapy. (orig.)

  16. Thyroid cell irradiation by radioiodines: a new Monte Carlo electron track-structure code

    Energy Technology Data Exchange (ETDEWEB)

    Champion, Christophe [Universite Paul Verlaine-Metz (France). Lab. de Physique Moleculaire et des Collisions]. E-mail:; Elbast, Mouhamad; Colas-Linhart, Nicole [Universite Paris 7 (France). Faculte de Medecine. Lab. de Biophysique; Ting-Di Wu [INSERM U759, Orsay (France). Institut Curie Recherche. Imagerie Integrative


    The most significant impact of the Chernobyl accident is the increased incidence of thyroid cancer among children who were exposed to short-lived radioiodines and 131-iodine. In order to accurately estimate the radiation dose provided by these radioiodines, it is necessary to know where iodine is incorporated. To do that, the distribution at the cellular level of newly organified iodine in the immature rat thyroid was performed using secondary ion mass microscopy (NanoSIMS{sup 50}). Actual dosimetric models take only into account the averaged energy and range of beta particles of the radio-elements and may, therefore, imperfectly describe the real distribution of dose deposit at the microscopic level around the point sources. Our approach is radically different since based on a track-structure Monte Carlo code allowing following-up of electrons down to low energies ({approx}= 10 eV) what permits a nanometric description of the irradiation physics. The numerical simulations were then performed by modelling the complete disintegrations of the short-lived iodine isotopes as well as of {sup 131}I in new born rat thyroids in order to take into account accurate histological and biological data for the thyroid gland. (author)

  17. Preparation, purification and primary bioevaluation of radioiodinated ofloxacin. An imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Kandil, Shaban; Seddik, Usama; Hussien, Hiba; Shaltot, Mohamed [Atomic Energy Authority, Cairo (Egypt). Cyclotron Project; El-Tabl, Abdou [Monofia Univ. (Egypt). Faculty of Science


    The broad-spectrum antibiotic agents have been demonstrated as promising diagnostic tools for early detection of infectious lesions. We set out ofloxacin (Oflo), a second-generation fluoroquinolone, for the radioiodination process. In particular, this was carried out with {sup 125}I via an electrophilic substitution reaction. The radiochemical yield was influenced by different factors; drug concentration, different oxidizing agents, e.g. chloramine-T, iodogen and n-bromosuccinimide, pH of medium, reaction time, temperature and different organic media. These parameters were studied to optimize the best conditions for labeling with ofloxacin. We found that radiolabeling in ethanol medium showed a 70% radiochemical yield of {sup 125}I-ofloxacin. The radioiodination was determined by means of TLC and HPLC. The cold labeled Oflo ({sup 127}I-Oflo) was prepared and controlled by HPLC. The cold labeled Oflo was also confirmed by NMR and MS techniques. Furthermore, biodistribution studies for labeled {sup 125}I-Oflo were examined in two independent groups (3 mice in each one); control and E. Coli-injected (inflamed). The radiotracer showed a good localization in muscle of thigh for inflamed group as compared to control. In conclusion, ofloxacine might be a promising target as an anti-inflammatory imaging agent.

  18. Radioiodine therapy of benign thyroid disorders: functional thyroid autonomy; Die Radioiodtherapie gutartiger Schilddruesenerkrankungen: Funktionelle Autonomie

    Energy Technology Data Exchange (ETDEWEB)

    Dunkelmann, S. [Klinik und Poliklinik fuer Nuklearmedizin, Zentrum fuer Radiologie, Univ. Rostock (Germany)


    In the last 15 years, several concepts have been developed to further improve the outcome of radioiodine therapy in functional thyroid autonomy. Results of radioiodine therapy in functional autonomy are considerably better than in Graves' disease. All of the currently-applied concepts offer healing rates of 75-100%, but they differ considerably in the hypothyreosis rates attained. The target volume can be precisely determined by sonography only in unifocal autonomy. In the case of multifocal and disseminated autonomy, the entire thyroid is taken as the target volume and the focal dose is reduced ('dosimetric compromise'). TcTUs-based dose concepts calculate the functionally autonomous volume from the TcTUs and replace the target volume by sonography, in the TcTUs-adapted dose concepts, sonographic target volume is left and the focal dose varied in dependence of the suppression uptake. The objective is to attain a high rate of success with a low rate of hypothyreosis. (orig.)

  19. Efficacy of Dietitian-instructed Low Iodine Diet for Radioiodine Remnant Tissue Ablation for Thyroid Cancer. (United States)

    Tamura, Mika; Nakada, Kunihiro; Tsuruhara, Reiko; Kawamura, Naoko; Kawagishi, Shizu; Furuta, Yasushi; Sugie, Hiroki; Sato, Yasushi; Sakurai, Masayuki


    We evaluated the significance of dietary instruction (DI) for patients who are going on a low iodine diet (LID) as a preparation for remnant tissue ablation for thyroid cancer. DI was done by a dietarian using a dedicated handbook we have developed. To assess the effect of LID on depleting body iodine, urinary iodine concentration (UIC) in patients with post-surgical papillary thyroid cancer was measured twice, before and after LID. UIC on the day of radioiodine administration was compared with radioiodine uptake (RU) in the remnant tissue. Additionally, the association between clinical and lifestyle-related features of patients and the outcome of LID were investigated. A questionnaire survey was conducted to determine whether the DI helped patients go on LID. The mean value of UIC after the one-week LID was decreased to about 15% of the baseline value. There was a significant inverse correlation between UIC and RU (r= -0.694). Age and UIC before the start of LID were linked to successful outcome of LID. In the questionnaire survey, 84% of the participants answered that the handbook helped them go on a LID. Likewise, 80% answered that they could manage their LID without using the boil-in-the-bag low iodine food. LID successfully decreased UIC in patients undergoing remnant tissue ablation. DI by a dietitian may make a practice of LID easier.

  20. Evaluation of a Number of Blood Biochemical Markers after Radioiodine Therapy in Papillary Thyroid Cancer Patients

    Directory of Open Access Journals (Sweden)

    Mehrossadat Alavi


    Full Text Available Background: This study aimed to assess several biochemical and oxidative stress parameters before and after radioiodine therapy in patients with well-differentiated thyroid cancer who consumed a low iodine diet and withdrawal of levothyroxine after total thyroidectomy. Methods:We enrolled 40 candidates for radioiodine therapy. Blood sampling was performed prior to as well as 72 h after consumption of 125-200 mCi of 131I. Total protein, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and creatinine were measured. Oxidative stress parameters that included malondialdehyde and protein carbonyl levels were also assessed. Results: There were significantly decreased total protein, creatinine, aspartate aminotransferase, and alanine aminotransferase levels (P<0.001 after treatment. However, malondialdehyde levels increased significantly (P<0.05 over the studied time. Conclusion: We found that radioactive iodine absorption in peripheral tissues due to a low-iodine diet and levothyroxine withdrawal could relieve iodine deficiency in the liver and kidneys which resulted in reduced total protein, aspartate aminotransferase, alanine aminotransferase, and creatinine levels. However, it induced oxidative stress by increasing malondialdehyde levels in the blood.

  1. Radioiodination and biological evaluation of Cladribine as potential agent for tumor imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bayoumi, Noha Anwer; Amin, Abeer M.; El-Kolaly, Mohamed T. [Egyptian Atomic Energy Authority, Cairo (Egypt). Hot Lab Center; Ismail, Nasser S.M.; Abouzid, Khaled A.M. [Ain-Shams Univ., Cairo (Egypt). Pharmaceutical Chemistry Dept.


    Cladribine, a purine analogue antimetabolite, was radioiodinated with {sup 125}I via direct electrophilic substitution reaction. The maximum radiochemical yield (92.5 ± 0.8%) was obtained when the reaction was done at ambient temperature for 30 min using 100 μg of Cladribine and 10 μg N-chlorosuccinamide (NCS) in 150 μL of 0.2 M phosphate buffer, pH 7. In vitro stability studies of HPLC purified {sup 125}I-Cladribine sample dissolved in 0.5 ml of 0.2 M phosphate buffer pH 7 at ambient temperature showed that {sup 125}I-Cladribine is stable up to 12 h post labeling. Biodistribution results revealed excretion of {sup 125}I-Cladribine mainly by kidneys. The uptake of {sup 125}I-Cladribine in the induced Ehrlich Ascites Carcinoma was 2.8 ± 0.4%ID/g at 1 h post injection with maximum tumor/muscle ratio of 5.5. The good uptake of {sup 125}I-Cladribine confirms the molecular docking studies results which indicate that iodinated Cladribine binds with polymerase enzyme with a good-CDOCKER energy. As a result, radioiodinated Cladribine may be used as a valuable agent for tumor diagnosis and therapy.

  2. A rare case of laryngotracheal chondrosarcoma in a patient with past history of radioiodine therapy for thyroid cancer

    Directory of Open Access Journals (Sweden)

    Gholamreza Mohajeri


    Full Text Available Tracheal chondrosarcoma is a rare malignant mesenchymal tumor and there are less than 15 reports in the literature. We report a rare case of laryngotracheal chondrosarcoma in a 74-year-old man. He gave a history of radioiodine therapy for thyroid papillary carcinoma about 24 years ago. Diagnostic steps, histological presentation, and therapy are described in detail.

  3. Radioiodine scintigraphy with SPECT/CT: an important diagnostic tool for thyroid cancer staging and risk stratification

    National Research Council Canada - National Science Library

    Avram, Anca M


    ...) but also the long-term follow-up strategy. This paper presents the progress made in the field of thyroid cancer imaging by application of SPECT/CT technology to radioiodine scintigraphy in both diagnostic and post-therapy settings and reviews...

  4. Assessment of exposure of workers to ionizing radiation from radioiodine and technetium in nuclear medicine departmental facilities

    Directory of Open Access Journals (Sweden)

    Grażyna Krajewska


    Full Text Available Background: Due to its use of ionising radiation, the field of nuclear medicine is a unique and significant part of medical diagnostics and patient treatment. The aim of this study was to assess the internal exposure of nuclear medicine employees to radioiodine 131I and technetium 99mTc as well as to assess the external exposure doses. Material and Methods: The radioiodine 131I and technetium 99mTc contents in the thyroid of staff members (about 100 persons dealing with these radionuclides have been measured in four departments of nuclear medicine. The measurements were conducted with a portable detection unit for in situ measurements of radioiodine and technetium. High sensitivity environmental thermoluminescent dosimeters (TLD were used to measure the external exposure dose. Results: The average values and ranges of radioiodine 131I activity measured in the thyroids of all of the medical units' employees were: 83 Bq (range: 70-250 Bq, 280 Bq (range: 70-4000 Bq, 275 Bq (range: 70-1000 Bq for technical staff, nuclear medicine staff and hospital services staff, respectively. The mean value of technetium 99mTc content in the thyroids of nuclear medicine staff was approximately 1500 Bq (range: 50- -1800 Bq. External exposure dose rates were in the range of 0.5-10 μGy/h. Conclusions: The calculated average effective dose for particular person caused by the inhalation of radioiodine 131I is below 5% of 20 mSv/year (occupational exposure limit. Med Pr 2013;64(5:625–630

  5. Current opinions on the radioiodine treatment of Graves' hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Woo; Lee, Jae Tae [School of Medicine, Kyungpook National Univ., Daegu (Korea, Republic of)


    Radioactive iodine therapy using I-131 for hyperthyroidism has been used for more than 50 years, and generally considered safe and devoid of major side effects. Appropriate patient selection criteria and clinical judgement concerning patient preparation should be employed for its optimal use. It has not been possible to resolve the trade-off between efficient definite cure of hyperthyroidism and the high incidence of post-therapy hypothyroidism. The dose of the I-131 needed to maintain euthyroid state remains an area of uncertainty and debate. Early side effects are uncommon and readily manageable. Other than the need for long-term monitoring and, in most cases, lifelong thyroid hormone treatment for late adverse consequences of this treatment remains only conjectural. We have reviewed general principles and recent advances in radioiodine treatment for Graves' hyperthyroidism, specially regarding to several controversies.

  6. Effects of Radioiodine Therapy on the Natural History of Graves' Ophtalmopathy

    Directory of Open Access Journals (Sweden)

    A Dreval


    Full Text Available 21 patients with Graves’ disease and Graves’ ophthalmopathy (GO received radioiodine treatment (RIT. Before 131-I therapy in all patients GO were non-active and no severe. Six patients not received any treatment before RIT; four patients received orbital radiotherapy and 11 patients received intravenous glucocorticoids. Thyreotoxicosis compensation were achieved by antithyroid medication before RIT. Antithyroid medication was stopped 10 days before RIT. Worsening of GO was seen on 47.7% patients 3 months after RIT, but only 9.5% of patients needed additional treatment GO. GO exacerbation take place in 90% of hypothyroid patients and its compensation reduced the symptoms of activity of GO for 3 months. 42.8% was without any symptoms of activity of GO by 9—12 months after RIT. Treatment of GO before RIT were improved the course of GO after RIT.

  7. Speciation of Radiocesium and Radioiodine in Aerosols from Tsukuba after the Fukushima Nuclear Accident

    DEFF Research Database (Denmark)

    Xu, Sheng; Zhang, Luyuan; Freeman, Stewart P. H. T.


    Aerosol samples were collected from Tsukuba, Japan, soon after the 2011 Fukushima nuclear accident and analyzed for speciation of radiocesium and radioiodine to explore their chemical behavior and isotopic ratios after the release. Most Cs-134 and Cs-137 were bound in organic matter (53......-91%) and some in water-soluble fractions (5-15%), whereas a negligible proportion of radiocesium remained in minerals. This pattern suggests that sulfate salts and organic matter may be the main carrier of Cs-bearing particles. The 129I in aerosol samples is contained in various proportions as soluble inorganic...... iodine (I- and IO3-), soluble organic iodine, and unextractable iodine. The measured mean I-129/I-131 atomic ratio of 16.0 +/- 2.2 is in good agreement with that measured from rainwater and consistent with ratios measured in surface soil samples. Together with other aerosols and seawater samples...

  8. The synthesis, radioiodination and preliminary biological study of the new carboxylic derivatives of dithizone

    Energy Technology Data Exchange (ETDEWEB)

    Garnuszek, Piotr; Licinska, Iwona; Mazurek, Aleksander P. [Drug Institute, Warsaw (Poland); Fiedor, Piotr [Transplantation Institute, Warsaw Medical Academy, Warsaw (Poland)


    Synthesis, characteristics and radioiodination of the new carboxylic derivatives of dithizone are described in this paper. We have applied the carboxy dithizones for preparation of radioactive compounds by coupling with [{sup 131}I]-histamine. Preliminary biological studies of the new radiodithizone were done in rats after two different application routs: peripheral i.v. injection and direct injection to splenic artery.Biodistribution of the carboxy dithizone-[{sup 131}I]-histamine conjugate (i.v. injection) was quite different than that for free [{sup 131}I]-histamine. However, uptake of activity in pancreas was low (0.81% g{sup -1} of tissue). Direct application of the conjugate to splenic artery resulted in high activity retention in pancreas after 30 and 45 min post injection (respectively 8.8 and 12.4% g{sup -1} of tissue) indicating potential usefulness of the new radiodithizone for in vivo monitoring of pancreas.

  9. The synthesis, radioiodination and preliminary biological study of the new carboxylic derivatives of dithizone. (United States)

    Garnuszek, P; Liciñska, I; Fiedor, P; Mazurek, A P


    Synthesis, characteristics and radioiodination of the new carboxylic derivatives of dithizone are described in this paper. We have applied the carboxy dithizones for preparation of radioactive compounds by coupling with [131I]-histamine. Preliminary biological studies of the new radiodithizone were done in rats after two different application routs: peripheral i.v. injection and direct injection to splenic artery. Biodistribution of the carboxy dithizone-[131I]-histamine conjugate (i.v. injection) was quite different than that for free [131I]-histamine. However, uptake of activity in pancreas was low (0.81% g-1 of tissue). Direct application of the conjugate to splenic artery resulted in high activity retention in pancreas after 30 and 45 min post injection (respectively 8.8 and 12.4% g-1 of tissue) indicating potential usefulness of the new radiodithizone for in vivo monitoring of pancreas.

  10. [Procedure guidelines for radioiodine therapy of differentiated thyroid cancer (version 2)]. (United States)

    Dietlein, M; Dressler, J; Farahati, J; Grünwald, F; Leisner, B; Moser, E; Reiners, C; Schicha, H; Schober, O


    The procedure guidelines for radioiodine therapy (RIT) of differentiated thyroid cancer (version 2) are the counter-part to the procedure guidelines for (131)I whole-body scintigraphy (version 2) and specify the interdisciplinary guidelines for thyroid cancer of the Deutsche Krebsgesellschaft and the Deutsche Gesellschaft für Chirurgie concerning the nuclear medicine part. Compared with version 1 facultative options for RIT can be chosen in special cases: ablative RIT for papillary microcarcinoma sperm cryoconservation. An interdisciplinary consensus is necessary whether the new TNM-classification (UICC, 6(th) edition, 2002) will lead to modified recommendations for surgical or nuclear medicine therapy, especially for the surgical completeness and for the ablative RIT of pT1 papillary cancer.

  11. Effect of reserpine on salivary gland radioiodine uptake in thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Levy, H.A.; Park, C.H.


    Nine patients with thyroid cancer were treated with reserpine in an attempt to reduce radiation exposure to the salivary glands from 100-150 mCi doses of I-131 therapy to thyroid remnants or metastases. Three control patients were not treated with reserpine but did receive 100-150 mCi of I-131. Parotid/background ratios of activity after radioablative doses of I-131 in patients not treated with reserpine were significantly higher than the patients treated with reserpine, and this was also true seven days after the radioablative dose. Combined therapy with reserpine, chewing gum, lemon candies, and hydration is suggested for the prevention of sialadenitis and xerostomia due to large doses of radioiodine.

  12. Relations between pathological markers and radioiodine can and {sup 18}F-FDG PET/CT findings in papillary thyroid cancer patients with recurrent cervical nodal metastases

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Won [Dept. of Nuclear Medicine, Catholic Kwandong University International St. Mary' s Hospital, Seoul (Korea, Republic of); Min, Hye Sook [Dept. of athology, Seoul National University Hospital, Seoul (Korea, Republic of); Lee, Sang Mi [Dept. of Nuclear Medicine, Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of); Kwon, Hyun Woo; Chung, June Key [Dept. of Nuclear Medicine,Seoul National University College of Medicine, Seoul (Korea, Republic of)


    The aim of this study was to investigate relationships between the immunohistochemical results and radioiodine scan and {sup 18}F-FDG PET findings in papillary thyroid cancer (PTC) patients with recurrent cervical nodal metastases. A total of 46 PTC patients who had undergone a radioiodine scan and/or {sup 18}F-FDG PET/CT and a subsequent operation on recurrent cervical lymph nodes were enrolled. Twenty-seven patients underwent {sup 18}F-FDG PET/CT, 8 underwent radioiodine scans, and 11 underwent both scans. In all surgical specimens, the immunoexpressions of thyroglobulin (Tg), sodium-iodide symporter (NIS), glucose transporter 1 (Glut-1), and somatostatin receptor 1 and 2A (SSTR1 and SSTR2A) were assessed, and associations between these expressions and radioiodine scan and {sup 18}F-FDG PET findings were evaluated. Of the 38 patients who underwent {sup 18}F-FDG PET/CT, all patients with weak Tg expression had positive {sup 18}F-FDG uptake, while only 45 % of the patients with moderate or strong Tg expression showed positive uptake (p = 0.01). The proportion of patients with positive {sup 18}F-FDG uptake increased as the degree of Glut-1 expression with luminal accentuation increased. Of the 19 patients who underwent a radioiodine scan, the proportion with positive radioiodine uptake was greater among patients with strong NIS and SSTR2A expression than among patients expressing these markers at weak levels (p = 0.04 for all). All three patients with weak Tg expression were negative for radioiodine uptake. The {sup 18}F-FDG uptakes of recurrent cervical nodes are related to strong Glut-1 expression with luminal accentuation and weak Tg expression, whereas radioiodine uptake is related to the strong expressions of NIS and SSTR2A.

  13. Results of a risk adapted and functional radioiodine therapy in Graves' disease

    Energy Technology Data Exchange (ETDEWEB)

    Dunkelmann, S.; Neumann, V.; Staub, U.; Groth, P.; Kuenstner, H.; Schuemichen, C. [Klinik und Poliklinik fuer Nuklearmedizin, Zentrum fuer Radiologie, Univ. Rostock (Germany)


    Aim of this study was to find out, if results of a functional orientated radioiodine therapy in Graves' disease could be optimized using a risk adopted dose concept. Patients, method: 351 patients with Graves' disease were treated for the first time between 11/97 and 8/01. The basic dose was 125 Gy, which was increased up to 250 Gy in a cumulative manner depending on clinical parameters (initial thyroid metabolism, thyroid volume, immunoreactivity). Two different methods of dosimetry were used. Occasional thyreostasis was withdrawn two days before the radioiodine test was started. Follow up was done on overage 8 {+-} 2,4 (4-17,2) months. TSH {>=}0,27 {mu}IU/mL confirmed as a measure of the success. Results: With improved pretherapeutic dosimetry and a mean target dose of 178 {+-} 31 Gy (n = 72) therapeutic success occurred in 66,7%, in 51,4% euthyreosis was restalled and in 15,3% of patients hypothyroidism was seen (TSH >4,20 {mu}IU/mL). With simplified pretherapeutic dosimetry and a mean target dose of 172 {+-} 29 Gy (n = 279) results were moderately impaired (63,8%, 40,1% and 23,7%). With increasing target dose therapeutic failure increased, as unsufficiently adopted risk factors for therapeutic failure turned out the initial thyroid metabolism, the TcTU(s) as the (h)TRAb titer. Conclusion: Functional orientated RIT can be optimized by including illness specific characteristics, principal limitations are a high initial thyroid metabolism, a large thyroid volume and a high (h)TRAb-titer. (orig.)

  14. Synthesis and investigation of a radioiodinated F3 peptide analog as a SPECT tumor imaging radioligand. (United States)

    Bhojani, Mahaveer S; Ranga, Rajesh; Luker, Gary D; Rehemtulla, Alnawaz; Ross, Brian D; Van Dort, Marcian E


    A radioiodinated derivative of the tumor-homing F3 peptide, (N-(2-{3-[(125)I]Iodobenzoyl}aminoethyl)maleimide-F3Cys peptide, [(125)I]IBMF3 was developed for investigation as a SPECT tumor imaging radioligand. For this purpose, we custom synthesized a modified F3 peptide analog (F3Cys) incorporating a C-terminal cysteine residue for site-specific attachment of a radioiodinated maleimide conjugating group. Initial proof-of-concept Fluorescence studies conducted with AlexaFluor 532 C(5) maleimide-labeled F3Cys showed distinct membrane and nuclear localization of F3Cys in MDA-MB-435 cells. Additionally, F3Cys conjugated with NIR fluorochrome AlexaFluor 647 C(2) maleimide demonstrated high tumor specific uptake in melanoma cancer MDA-MB-435 and lung cancer A549 xenografts in nude mice whereas a similarly labeled control peptide did not show any tumor uptake. These results were also confirmed by ex vivo tissue analysis. No-carrier-added [(125)I]IBMF3 was synthesized by a radioiododestannylation approach in 73% overall radiochemical yield. In vitro cell uptake studies conducted with [(125)I]IBMF3 displayed a 5-fold increase in its cell uptake at 4 h when compared to controls. SPECT imaging studies with [(125)I]IBMF3 in tumor bearing nude mice showed clear visualization of MDA-MB-435 xenografts on systemic administration. These studies demonstrate a potential utility of F3 peptide-based radioligands for tumor imaging with PET or SPECT techniques.

  15. Enhancement of radioiodine uptake in hyperthyroidism with hydrochlorothiazide: a prospective randomised control study

    Energy Technology Data Exchange (ETDEWEB)

    Tepmongkol, Supatporn [Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330 (Thailand)


    The aim of this study was to determine whether hydrochlorothiazide (HCTZ) could improve radioiodine uptake in low-uptake hyperthyroid patients. Eighteen hyperthyroid patients with low 3-h and 24-h iodine-131 uptake were recruited to the study. Eleven patients were assigned to the HCTZ group, and seven to the control group. Two weeks after the first, baseline uptake study, a second uptake study was performed. Patients in both groups had a low-iodine diet after the first uptake study. In the HCTZ group, 50 mg of HCTZ was administered twice a day for 5 days prior to the second uptake study. Improvement in uptake at 3 and 24 h in the second uptake study, as compared with the baseline study, was assessed within and between groups. In the control group, compared with the baseline study there was a significant improvement in uptake at 3 h (P=0.03) but a non-significant improvement at 24 h (P=0.07). In the HCTZ group, significant improvements were observed at both 3 h (P=0.0005) and 24 h (P=2.28 x 10{sup -5}). Patients in the HCTZ group had statistically greater improvement in uptake at both 3 h and 24 h compared with the control group (P=0.003 and 0.0008, respectively). There was a 7.18-fold average improvement in uptake in the HCTZ group at 24 h, compared with only a 1.33-fold improvement in the control group. Administration of HCTZ significantly improves 24-h radioiodine uptake in high-iodide pool, low-uptake hyperthyroid patients compared with patients who have received a low-iodine diet alone. (orig.)

  16. Differentiated thyroid cancer. New concept of radioiodine ablation; Differenziertes Schilddruesenkarzinom. Fortschritte bei der Radioiodablation

    Energy Technology Data Exchange (ETDEWEB)

    Dietlein, M.; Kobe, C. [Universitaetsklinikum Koeln (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Universitaetsklinikum Koeln (Germany), Zentrum fuer Integrierte Onkologie Koeln-Bonn; Luster, M. [Universitaetsklinikum Ulm (Germany). Klinik und Poliklinik fuer Nuklearmedizin


    Ablative radioiodine therapy is the treatment of choice in patients with differentiated thyroid cancer, the only exception being the unifocal, very small papillary thyroid cancer. The TSH-stimulation can be achieved by a waiting period for 2-3 weeks after thyroidectomy without medication or by the use of recombinant human TSH (rhTSH). Both options lead to high success rates. 'Single dose cure' using activities between 1.85 and 3.7 GBq {sup 131}I is standard. Since 2010 rhTSH is approved by the EMA for the indications pT1-4, N0-1, cM0. Survey studies did not find any inferiority of ablation with rhTSH or iatrogenic hypothyroidism in the high-risk patient group. Renal clearance is not reduced after rhTSH administration, thus the {sup 131}I blood dose and the whole body doses are lower in patients under rhTSH. Comparing identical {sup 131}I activities after endogeneous or exogeneous stimulation, rhTSH will minimize the acute adverse effects of {sup 131}I. A short-term withdrawal of levothyroxine some days before rhTSH-injection lowers the iodine plasma level, which may be advantageous for the ablation success if lower 131I activities are used. A rhTSH-based diagnostic {sup 131}I whole-body scintigraphy 3-6 months after ablation is standard for therapy control. At this time, the rhTSH-stimulated thyroglobulin-level is essential for a personalized risk stratification. Tg-measurements by a second generation assay should be used for follow-up care. Metaanalyses have shown that radioiodine ablation lowers the mortality rate, the risk of locoregional recurrences and the risk of late metastasizing. Therefore, ablation has shown a clear benefit. (orig.)

  17. Radioiodine therapy in benign thyroid disorders. Evaluation of French nuclear medicine practices. (United States)

    Bernard, Delphine; Desruet, Marie Dominique; Wolf, Marianne; Roux, Julie; Boin, Camille; Mazet, Roseline; Gallazzini, Céline; Calizzano, Alex; Vuillez, Jean-Philippe; Allenet, Benoît; Fagret, Daniel


    Radioiodine is currently used routinely in the treatment of hyperthyroidism including Graves' disease (GD), toxic multinodular goitre (TMNG) and toxic solitary nodule (TSN) but no consensus exists on the most appropriate way to prescribe iodine--fixed dose or calculated doses based on the gland size or turnover of (131)I. We carried out the first nationwide French survey assessing the current practices in radioiodine treatment of hyperthyroidism. A questionnaire was sent to French nuclear medicine hospital units and cancer treatment centres (n=69) about their practices in 2012. Euthyroidism was considered the successful outcome for 33% of respondents, whereas hypothyroidism was the aim in 26% of cases. Fixed activities were the commonest therapeutic approach (60.0% of GD prescribed doses and 72.5% for TMNG and TSN), followed by calculated activities from Marinelli's formula (based on a single uptake value and thyroid volume). The fixed administered dose was chosen from between 1 to 3 levels of standard doses, depending on the patient characteristics. Factors influencing this choice were disease, with a median of 370 MBq for GD and 555 MBq for TSN and TMNG, thyroid volume (59%) and uptake (52%) with (131)I or (99m)Tc. Even physicians using fixed doses performed pretherapeutic thyroid scan (98%). This study shows that practices concerning the prescription of (131)I therapeutic doses are heterogeneous. But the current trend in France, as in Europe, is the administration of fixed doses. The study provides the baseline data for exploring the evolution of French clinical practices. Copyright © 2014. Published by Elsevier Masson SAS.

  18. Controlled environmental radioiodine tests at the national reactor testing station. 1965 progress report

    Energy Technology Data Exchange (ETDEWEB)

    Adams, D.R.; Bunch, D.F.; Gammill, W.P.; Hawley, C.A. Jr.; Markee, E.H.; Tiernan, M.W.


    The CERT project consists of a series of planned releases of radioiodine over different vegetation and during various meteorological conditions, with the prime objective being to measure the relationships involved in the passage of radioiodine through the air-vegetation-cow-milk-human chain. The results of the first five tests in the series, which started in the spring of 1963 and is continuing, are reported. Each test was conducted under measured meteorological conditions and over prepared sampling and grazing courses. Two tests were made over open-range type vegetation, two over irrigated pastures, and one over snow-covered ground. Two tests were conducted under lapse conditions, two under inversion conditions, and one under neutral conditions. In each case, known quantities of elemental /sup 131/I/sub 2/ were released. Relationships determined included air-grass ratios (deposition velocities) which ranged from 0.1 to 1.0 cm/sec; effective half life of /sup 131/I on grass of 3.5 days and 5.5 days; the time of peak activity in milk at two days following a release; milk-grass ratio (C/1:C/g); total /sup 131/I secreted in milk by cows to that ingested by cows; adult human thyroid uptake fraction (inhalation); and based on a breathing rate of 20 m/sup 3//24 hours, the ratio between infinity mills ingestion dose and infinity inhalation dose for a single release was calculated. Data, descriptions of methods, and calculations are reported. Discussions of resuspension factors and particle sizes and behavior are also included.

  19. Radioiodine therapy (United States)

    ... need to avoid: Foods that contain iodized salt Dairy products, eggs Seafood and seaweed Soybeans or soy- ... away from small children and pregnant women Not return to work Sleep in a separate bed from ...

  20. Radioiodinated (aminostyryl)pyridinium (ASP) dyes: New cell membrane probes for labeling mixed leukocytes and lymphocytes for diagnostic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lambert, Carol; Mease, Ronnie C.; Avren, Lee; Le, Truc; Sabet, Hassan; McAfee, John G


    We prepared [({sup 125}I({sup 131}I))]iodo-(aminostyryl)pyridinium dyes from tributylstannyl precursors. ASP 7a and 7b labeled leukocytes ex vivo (70-94%) using saline with or without washing plasma from cells. Viability of peripheral blood lymphocytes (PBLs) (dogs, rats) and splenic lymphocytes (rats) labeled with 7a and 7b (71-82%) was unchanged after labeling ({>=}88%). Canine 7b-leukocytes showed higher uptake in inflammatory lesions than did {sup 111}In-oxine leukocytes. At 3 h, aspirates contained more radioiodine than {sup 111}In (1.65:1 to 22:1) and radioiodine was cell bound. ROI measurements (3 h) gave abscess to contralateral knee ratios of 12.3 and 10.6 for {sup 131}I-7b vs. 4.8 and 2.3 for {sup 111}In-oxine.

  1. A comparison of Coomassie blue dye with radioiodinated albumin as an indicator for plasma volume estimation in human subjects (United States)

    Menzies, Ian S.


    Plasma volume has been estimated in 10 human subjects using Coomassie blue and 131I radioiodinated human serum albumin dilution methods simultaneously. Three different methods of correction used by previous workers to overcome the error due to early dye loss were applied. Satisfactory agreement with the established radioiodinated albumin method was only obtained by extrapolation of the semilogarithmic plot of Coomassie blue plasma dye concentration between five and 10 minutes to the time of injection. The significance of the controversial Evans blue `mixing curve' is discussed. An analogous phase in the Coomassie blue disappearance slope is considered to be due to initial rapid loss of dye from the circulation rather than to the process of mixing. It is shown that Coomassie blue fulfils the criteria listed in the discussion for plasma volume estimation. PMID:4160095

  2. In Vitro Incorporation of Radioiodinated Eugenol on Adenocarcinoma Cell Lines (Caco2, MCF7, and PC3). (United States)

    Dervis, Emine; Yurt Kilcar, Ayfer; Medine, Emin Ilker; Tekin, Volkan; Cetkin, Buse; Uygur, Emre; Muftuler, Fazilet Zumrut Biber


    Recently, the synthesis of radiolabeled plant origin compounds has been increased due to their high uptake on some cancer cell lines. Eugenol (EUG), a phenolic natural compound in the essential oils of different spices such as Syzygium aromaticum (clove), Pimenta racemosa (bay leaves), and Cinnamomum verum (cinnamon leaf), has been exploited for various medicinal applications. EUG has antiviral, antioxidant, and anti-inflammatory functions and several anticancer properties. The objective of this article is to synthesize radioiodinated (131I) EUG and investigate its effect on Caco2, MCF7, and PC3 adenocarcinoma cell lines. It is observed that radioiodinated EUG would have potential on therapy and imaging due to its notable uptakes in studied cells.

  3. Instantaneous radioiodination of rose bengal at room temperature and a cold-kit therefor. [DOE patent application (United States)

    O'Brien, H. Jr.; Hupf, H.B.; Wanek, P.M.

    The disclosure relates to the radioiodination of rose bengal at room temperature and a cold-kit therefor. A purified rose bengal tablet is stirred into acidified ethanol at or near room temperature, until a suspension forms. Reductant-free /sup 125/I/sup -/ is added and the resulting mixture stands until the exchange label reaction occurs at room temperature. A solution of sterile isotonic phosphate buffer and sodium hydroxide is added and the final resulting mixture is sterilized by filtration.

  4. Pyramidal lobe decreases endogenous TSH stimulation without impact on radio-iodine therapy outcome in patients with differentiated thyroid cancer. (United States)

    Sawicka-Gutaj, Nadia; Klimowicz, Aleksandra; Sowinski, Jerzy; Oleksa, Robert; Gryczynska, Maria; Wyszomirska, Anna; Czarnywojtek, Agata; Ruchala, Marek


    The aim of the study was to assess the frequency of pyramidal lobe (PL) detected in iodine-131 (I-131) scans of thyroid bed in patients after thyroidectomy for differentiated thyroid cancer (DTC) and to investigate influence of PL on endogenous thyrotropin (TSH) stimulation as well as on the effects of the radio-iodine ablation in one-year follow-up. This study was designed as a retrospective analysis of 302 radio-iodine neck scans of patients thyroidectomized due to DTC. The study population was selected from patients with PL detected in thyroid bed scintigraphy. Patients without PL were included to the control group. The study and the control groups did not differ in age, sex of patients, histological type and stage of the DTC. Pyramidal lobes were found in 30.5% of all patients. Patients in the study group underwent repeat surgery more often than controls without PL. Preablative TSH level in patients with PL was statistically lower than in the control group, in contrast to free thyroid hormones, which were higher in patients with PL. Preablative and postablative TSH-stimulated thyroglobulin (Tg) and antibodies against thyroglobulin (TgAbs) were measured in both groups, and comparison did not reveal differences. Moreover, for the per-patient analysis, sites of uptake in whole body scintigraphy performed 1 year after radio-iodine remnant ablation (RRA) did not differ between the study and the control groups. Pyramidal lobe decreases endogenous TSH stimulation without impact on radio-iodine therapy outcome in patients with DTC. Copyright © 2014. Published by Elsevier Masson SAS.

  5. Investigation of a Potential Scintigraphic Tracer for Imaging Apoptosis: Radioiodinated Annexin V-Kunitz Protease Inhibitor Fusion Protein

    Directory of Open Access Journals (Sweden)

    Mei-Hsiu Liao


    Full Text Available Radiolabeled annexin V (ANV has been widely used for imaging cell apoptosis. Recently, a novel ANV-Kunitz-type protease inhibitor fusion protein, ANV-6L15, was found to be a promising probe for improved apoptosis detection based on its higher affinity to phosphatidylserine (PS compared to native ANV. The present paper investigates the feasibility of apoptosis detection using radioiodinated ANV-6L15. Native ANV and ANV-6L15 were labeled with iodine-123 and iodine-125 using Iodogen method. The binding between the radioiodinated proteins and erythrocyte ghosts or chemical-induced apoptotic cells was examined. ANV-6L15 can be radioiodinated with high yield (40%−60% and excellent radiochemical purity (>95%. 123I-ANV-6L15 exhibited a higher binding ratio to erythrocyte ghosts and apoptotic cells compared to 123I-ANV. The biodistribution of 123I-ANV-6L15 in mice was also characterized. 123I-ANV-6L15 was rapidly cleared from the blood. High uptake in the liver and the kidneys may limit the evaluation of apoptosis in abdominal regions. Our data suggest that radiolabled ANV-6L15 may be a better scintigraphic tracer than native ANV for apoptosis detection.

  6. Graves' disease and radioiodine therapy. Is success of ablation dependent on the choice of thyreostatic medication?

    Energy Technology Data Exchange (ETDEWEB)

    Kobe, C.; Weber, I.; Eschner, W.; Sudbrock, F.; Schmidt, M.; Dietlein, M.; Schicha, H. [Dept. of Nuclear Medicine, Univ. of Cologne (Germany)


    Aim: this study was performed to analyse the impact of the choice of antithyroid drugs (ATD) on the outcome of ablative radioiodine therapy (RIT) in patients with Graves' disease. Patients, material, methods: a total of 571 consecutive patients were observed for 12 months after RIT between July 2001 and June 2004. Inclusion criteria were the confirmed diagnosis of Graves' disease, compensation of hyperthyroidism and withdrawal of ATD two days before preliminary radioiodine-testing and RIT. The intended dose of 250 Gy was calculated from the results of the radioiodine test and the therapeutically achieved dose was measured by serial uptake measurements. The end-point measure was thyroid function 12 months offer RIT; success was defined as elimination of hyperthyroidism. The pretreatment ATD was retrospectively correlated with the results achieved. Results: relief from hyperthyroidism was achieved in 96% of patients. 472 patients were treated with carbimazole or methimazole (CMI) and 61 with propylthiouracil (PTU). 38 patients had no thyrostatic drugs (ND) prior to RIT. The success rate was equal in all groups (CMI 451/472; PTU 61/61; ND 37/38; p = 0.22). Conclusion: thyrostatic treatment with PTU achieves excellent results in ablative RIT, using an accurate dosimetric approach with an achieved post-therapeutic dose of more than 200 Gy. (orig.)

  7. Clinical Studies of Nonpharmacological Methods to Minimize Salivary Gland Damage after Radioiodine Therapy of Differentiated Thyroid Carcinoma: Systematic Review

    Directory of Open Access Journals (Sweden)

    Andri Christou


    Full Text Available Purpose. To systematically review clinical studies examining the effectiveness of nonpharmacological methods to prevent/minimize salivary gland damage due to radioiodine treatment of differentiated thyroid carcinoma (DTC. Methods. Reports on relevant trials were identified by searching the PubMed, CINHAL, Cochrane, and Scopus electronic databases covering the period 01/2000–10/2015. Inclusion/exclusion criteria were prespecified. Search yielded eight studies that were reviewed by four of the present authors. Results. Nonpharmacological methods used in trials may reduce salivary gland damage induced by radioiodine. Sialogogues such as lemon candy, vitamin E, lemon juice, and lemon slice reduced such damage significantly (p<0.0001, p<0.05, p<0.10, and p<0.05, resp.. Parotid gland massage also reduced the salivary damage significantly (p<0.001. Additionally, vitamin C had some limited effect (p=0.37, whereas no effect was present in the case of chewing gum (p=0.99. Conclusion. The review showed that, among nonpharmacological interventions, sialogogues and parotid gland massage had the greatest impact on reducing salivary damage induced by radioiodine therapy of DTC. However, the studies retrieved were limited in number, sample size, strength of evidence, and generalizability. More randomized controlled trials of these methods with multicenter scope and larger sample sizes will provide more systematic and reliable results allowing more definitive conclusions.

  8. Modeling of thermal properties of a TeO 2 target for radioiodine production (United States)

    Čomor, J. J.; Stevanović, Ž.; Rajčević, M.; Košutić, D.


    Three radionuclides of iodine ( 120I, 123I and 124I) are of great interest for modern nuclear medical diagnostics. They can be all produced by the (p,n) nuclear reaction using isotopically enriched solid TeO 2 targets. The produced radioiodine can be rapidly separated from the target material by dry-distillation from the melted target after the irradiation. Since TeO 2 has low thermal conductivity, the most critical issue in the design of a production target is the provision of its effective cooling in order to avoid melting of the oxide layer during the irradiation. A compact solid target irradiation system (COSTIS) has been designed for the irradiation of TeO 2 targets, suitable for routine production of radioiodine. The target is a circular Pt-disk that carries the TeO 2 melted into a circular grove in the center of the disk. The target coin is manually inserted into COSTIS, fixed pneumatically in the irradiation position, released remotely after irradiation and falls down driven by gravity into a transport container. The engineering design of the cavity for helium cooling of the front face of TeO 2 and the impinging water jet cooling the back face of the target disk was done based on a simulation of the thermal behavior of the target during the irradiation. A straightforward numerical method for the prediction of the thermal properties of the solid target has been developed. The approach is based on calculations without using the common practice of Prandtl and Nusselt empirical correlation. The fluid flow description in the boundary layer was refined in such a way, that the heat flux, exchanged between the solid and fluid, is obtained directly from Fourier law. The governing equations are based on the local thermodynamic equilibrium and conservation equation of mass, momentum and energy. In order to solve the set of governing equations, the finite-volume method is used. This procedure gives rapid answers whether the proposed geometry satisfies the design

  9. Effect of a Low Iodine Diet vs. Restricted Iodine Diet on Postsurgical Preparation for Radioiodine Ablation Therapy in Thyroid Carcinoma Patients. (United States)

    Lim, Chi Young; Kim, Jung-Yeon; Yoon, Mi-Jin; Chang, Hang Seok; Park, Cheong Soo; Chung, Woong Youn


    The radioiodine ablation therapy is required for patients who underwent a total thyroidectomy. Through a comparative review of a low iodine diet (LID) and a restricted iodine diet (RID), the study aims to suggest guidelines that are suitable for the conditions of Korea. The study was conducted with 101 patients. With 24-hour urine samples from the patients after a 2-week restricted diet and after a 4-week restricted diet, the amount of iodine in the urine was estimated. The consumed radioiodine amounts for 2 hours and 24 hours were calculated. This study was conducted with 47 LID patients and 54 RID patients. The amounts of iodine in urine, the 2-week case and 4-week case for each group showed no significant differences. The amounts of iodine in urine between the two groups were both included in the range of the criteria for radioiodine ablation therapy. Also, 2 hours and 24 hours radioiodine consumption measured after 4-week restrictive diet did not show statistical differences between two groups. A 2-week RID can be considered as a type of radioiodine ablation therapy after patients undergo a total thyroidectomy.

  10. [Postoperative radioiodine ablation in patients with low risk differentiated thyroid carcinoma]. (United States)

    Díez, Juan J; Grande, Enrique; Iglesias, Pedro


    Most patients with newly diagnosed differentiated thyroid carcinoma have tumors with low risk of mortality and recurrence. Standard therapy has been total or near total thyroidectomy followed by postoperative radioiodine remnant ablation (RRA). Although RRA provides benefits, current clinical guidelines do not recommend it universally, since an increase in disease-free survival or a decrease in mortality in low risk patients has not been demonstrated so far. Advancements in our understanding of the biological behavior of thyroid cancer have been translated into the clinic in a personalized approach to the patients based on their individual risk of recurrence and mortality. Current evidence suggests that RRA is not indicated in most low-risk patients, especially those with papillary carcinomas smaller than 1cm, without extrathyroidal extension, unfavorable histology, lymph node involvement or distant metastases. Follow-up of these patients with serial measurements of serum thyroglobulin and neck ultrasound is adequate. Careful evaluation of all risk factors of clinical relevance will allow a more realistic assessment of each individual patient. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  11. Preparation with recombinant humanized thyroid-stimulating hormone before radioiodine ablation after thyroidectomy: a systematic review. (United States)

    Yoo, J; Cosby, R; Driedger, A


    Standard treatment for differentiated thyroid cancer is thyroidectomy followed in selected cases by radioiodine ablation (RA). Recombinant humanized thyroid-stimulating hormone (rhTSH) is an exogenous source of tsh that can be administered to obviate the need for hormone withdrawal. In this systematic review, we analysed the evidence for the therapeutic use of (rhTSH for RA preparation. A systematic review of the MEDLINE and EMBASE databases from 1996 through January 2008 selected articles reporting randomized controlled trials, cohort studies, and retrospective studies published in English that compared ra using rhTSH with standard hormone withdrawal. Stimulation by rhTSH is equivalent to thyroid hormone withdrawal in achieving ablation while avoiding detrimental symptoms of hypothyroidism and significantly lowering the whole-body radiation dose. Furthermore, rhTSH may be the only option for patients who either cannot raise endogenous tsh or who would be at risk from the morbidity of hypothyroidism. Based on the results of validated instruments of physical and mental performance, there is agreement that rhTSH maintains a better quality of life. Studies of cost-effectiveness found that rhTSH-prepared patients lost less time from work and required fewer encounters with health care providers.

  12. Results from phase 2 of the radioiodine test facility experimental program

    Energy Technology Data Exchange (ETDEWEB)

    Ball, J.M.; Kupferschmid, W.C.H.; Wren, J.C. [Atomic Energy of Canada Ltd., Pinawa, MB (Canada). Whiteshell Labs.


    A series of intermediate-scale experiments were conducted in the Radioiodine Test Facility (RTF) in a vinyl-painted, zinc-primer coated, carbon steel vessel in order to assess the effects of vinyl surfaces on iodine volatility in both the presence and absence of radiation. This test series, Phase 2 of a larger, comprehensive program assessing a variety of containment surfaces, also examined the effects of organic (i.e., methyl ethyl ketone) and inorganic (i.e., hydrazine) additives, pH, and venting on the aqueous chemistry and volatility of solutions initially containing cesium iodide. These tests have clearly demonstrated that organics are released to the aqueous phase from the vinyl coating and that, under radiation conditions, these organics can have a significant effect on the formation of volatile iodine species. In particular, the RTF results suggest that radiolytic decomposition of the released organics results in dramatic reductions in pH and dissolved oxygen concentration, which in turn are responsible for increased formation of molecular iodine and organic iodides. When the pH was maintained at 10 (Test 3), much lower iodine volatility was observed; low iodine volatility was also observed in the absence of radiation. This test series also demonstrated that vinyl surfaces, particularly those in contact with the gas phase, were a sink for iodine. (author) 4 figs., 6 tabs., 17 refs.

  13. Cytogenetic biodosimetry and dose-rate effect after radioiodine therapy for thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Khvostunov, Igor K. [Russian Ministry of Health Care, A.F. Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Centre, Obninsk, Kaluga Region (Russian Federation); Nagasaki University, Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute, Nagasaki (Japan); Saenko, Vladimir A.; Yamashita, Shunichi [Nagasaki University, Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute, Nagasaki (Japan); Krylov, Valeri; Rodichev, Andrei [Russian Ministry of Health Care, A.F. Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Centre, Obninsk, Kaluga Region (Russian Federation)


    This study set out to investigate chromosomal damage in peripheral blood lymphocytes of thyroid cancer patients receiving {sup 131}I for thyroid remnant ablation or treatment of metastatic disease. The observed chromosomal damage was further converted to the estimates of whole-body dose to project the adverse side effects. Chromosomal aberration analysis was performed in 24 patients treated for the first time or after multiple courses. Blood samples were collected before treatment and 3 or 4 days after administration of 2-4 GBq of {sup 131}I. Both conventional cytogenetic and chromosome 2, 4 and 12 painting assays were used. To account for dose-rate effect, a dose-protraction factor was applied to calculate the whole-body dose. The mean dose was 0.62 Gy (95% CI: 0.44-0.77 Gy) in the subgroup of patients treated one time and 0.67 Gy (95% CI: 0.03-1.00 Gy) in re-treated patients. These dose estimates are about 1.7-fold higher than those disregarding the effect of exposure duration. In re-treated patients, the neglected dose-rate effect can result in underestimation of the cumulative whole-body dose by the factor ranging from 2.6 to 6.8. Elevated frequency of chromosomal aberrations observed in re-treated patients before radioiodine therapy allows estimation of a cumulative dose received from all previous treatments. (orig.)

  14. The potential of radioiodinated (-)-m-iodovesamicol for diagnosing cholinergic deficit dementia

    Energy Technology Data Exchange (ETDEWEB)

    Shibaa, Kazuhiro E-mail:; Mori, Hirofumi; Ikeda, Eiji; Sumiya, Hisashi; Tonami, Norihisa


    We investigated changes in the brain distribution of (-)-[{sup 125}I]-m-iodovesamicol [(-)-[{sup 125}I]mIV] in cholinergic denervation rats produced by a unilateral lesion of the nucleus basalis magnocellularis (NBM). Dual-tracer ex vivo autoradiographic analysis using (-)-[{sup 125}I]mIV and [{sup 99m}Tc]HMPAO was conducted to the effect of regional cerebral perfusion on the brain distribution of (-)-[{sup 125}I]mIV in a unilateral NBM-lesioned rat. (-)-[{sup 125}I]mIV binding in the ipsilateral cortex to the lesion significantly reduced by 10.4 %, compared with that in the contralateral cortex, while (-)-[{sup 125}I]mIV binding in the ipsilateral caudate putamen, hippocampus and thalamus did not change. The rate of reduction in the (-)-[{sup 125}I]mIV binding (10.4 %) was significantly higher than that of [{sup 99m}Tc]HMPAO accumulation (4.0%) in the ipsilateral cortex to the lesion (P < 0.01). These results suggested that radioiodinated (-)-mIV may be useful in the study of dementia characterized by degeneration of the cholinergic neurotransmitter system, such as Alzheimer's disease.

  15. Cytogenetic effects of radioiodine therapy: a 20-year follow-up study

    Energy Technology Data Exchange (ETDEWEB)

    Livingston, Gordon K. [Oak Ridge Institute for Science and Education, Radiation Emergency Assistance Center/Training Site, Oak Ridge, TN (United States); Khvostunov, Igor K. [Medical Radiological Research Center, Obninsk, Kaluga Region (Russian Federation); Gregoire, Eric [Institut de Radioprotection et de Surete Nucleaire, PRP-HOM/SRBE/LDB, BP 17, Fontenay aux roses Cedex (France); Barquinero, Joan-Francesc [Universtitat Autonoma de Barcelona, Facultat de Biociencies, Cerdanyola del Valles (Spain); Shi, Lin; Tashiro, Satoshi [Hiroshima University, Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima (Japan)


    The purpose of this study was to compare cytogenetic data in a patient before and after treatment with radioiodine to evaluate the assays in the context of biological dosimetry. We studied a 34-year-old male patient who underwent a total thyroidectomy followed by ablation therapy with {sup 131}I (19.28 GBq) for a papillary thyroid carcinoma. The patient provided blood samples before treatment and then serial samples at monthly intervals during the first year period and quarterly intervals for 5 years and finally 20 years after treatment. A micronucleus assay, dicentric assay, FISH method and G-banding were used to detect and measure DNA damage in circulating peripheral blood lymphocytes of the patient. The results showed that radiation-induced cytogenetic effects persisted for many years after treatment as shown by elevated micronuclei and chromosome aberrations as a result of exposure to {sup 131}I. At 5 years after treatment, the micronucleus count was tenfold higher than the pre-exposure frequency. Shortly after the treatment, micronucleus counts produced a dose estimate of 0.47 ± 0.09 Gy. The dose to the patient evaluated retrospectively using FISH-measured translocations was 0.70 ± 0.16 Gy. Overall, our results show that the micronucleus assay is a retrospective biomarker of low-dose radiation exposure. However, this method is not able to determine local dose to the target tissue which in this case was any residual thyroid cells plus metastases of thyroidal origin. (orig.)

  16. Patients' perceptions and views of surgery and radioiodine ablation in the definitive management of Graves' disease. (United States)

    Hookham, Jessica; Truran, Peter; Allahabadia, Amit; Balasubramanian, Sabapathy P


    Patients' perceptions and preferences influence the choice of radioiodine ablation (RIA) or surgery in the definitive management of Graves' disease. This study aimed to evaluate their concerns, experiences and satisfaction following definitive treatment. A postal survey of patients who had treatment with surgery or RIA between January 2011 and June 2013 for Graves' disease was conducted. Of 214 patients, 136 (64%) responded. The majority of patients felt actively involved in decision making (83.8%) and were satisfied (84.9%) with their treatment. Compared with RIA, patients who underwent surgery were more satisfied with their treatment (p=0.008). Discussion with the doctor was the most useful aid to decision making. Feeling involved in decision-making process was associated with improved satisfaction (pdisease were common reasons for not choosing RIA. Ongoing concerns were hypothyroidism, scarring and eye problems after surgery and hypothyroidism and eye problems after RIA. This study provides insight into patients' experiences of surgery and RIA for Graves' disease and reinforces the importance of patient involvement in the decision-making process. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  17. Direct and indirect radioiodination of protein: comparative study of chemotactic peptide labeling; Radioiodacao de proteina por via direta e indireta: estudo comparativo da marcacao de peptideo quimiotatico

    Energy Technology Data Exchange (ETDEWEB)

    Lavinas, Tatiana


    The development of simple methods for protein radioiodination have stimulated the use of radioiodinated peptides in vivo. There are two basic methods for labeling proteins with radioiodine: direct labeling, reaction of an electrophilic radioiodine with functional activated groups on protein, like the phenol ring in the tyrosine residue, and the conjugation of a previously radioiodinated molecule to the protein, referred as indirect method. The great problem related to the direct radioiodination of proteins is the in vivo dehalogenation. This problem can be minimized if a non-phenolic prosthetic group is used in the indirect radioiodination of the peptide. The ATE prosthetic group, N-succinimidyl 3-(tri-n-butylstannyl) benzoate, when radioiodinated by electrophilic iododestannilation produces N-succinimidyl 3-[{sup 123}l/{sup 131}l] iodine benzoate (SIB) that is subsequently conjugated to the protein by the acylation of the lysine group. There are many radiopharmaceuticals employed in scintigraphic images of infection and inflammation used with some limitations. These limitations stimulated the improvement of a new class of radiopharmaceuticals, the receptor-specific related labeled peptides, as the mediators of the inflammatory response, that presents high affinity by receptors expressed in the inflammation process, and fast clearance from blood and non-target tissues. One of these molecules is the synthetic chemotactic peptide fNleLFNIeYK that presents potent chemotaxis for leukocytes, with high affinity by the receptors presented in polymorphonuclear leukocytes and mononuclear phagocytes. The objective of this work included the synthesis of ATE prosthetic group and comparative radioiodination of the chemotactic peptide fNleLFNIeYK by direct and indirect methods, with radiochemical purity determination and evaluation of in vivo and in vitro stability of the compounds. This work presented an original contribution in the comparative biological distribution studies

  18. Clinical Outcome of Remnant Thyroid Ablation with Low Dose Radioiodine in Korean Patients with Low to Intermediate-risk Thyroid Cancer. (United States)

    Ha, Seunggyun; Oh, So Won; Kim, Yu Kyeong; Koo, Do Hoon; Jung, Young Ho; Yi, Ka Hee; Chung, June-Key


    Radioiodine activity required for remnant thyroid ablation is of great concern, to avoid unnecessary exposure to radiation and minimize adverse effects. We investigated clinical outcomes of remnant thyroid ablation with a low radioiodine activity in Korean patients with low to intermediate-risk thyroid cancer. For remnant thyroid ablation, 176 patients received radioiodine of 1.1 GBq, under a standard thyroid hormone withdrawal and a low iodine diet protocol. Serum levels of thyroid stimulating hormone stimulated thyroglobulin (off-Tg) and thyroglobulin-antibody (Tg-Ab), and a post-therapy whole body scan (RxWBS) were evaluated. Completion of remnant ablation was considered when there was no visible uptake on RxWBS and undetectable off-Tg (thyroid ablation in patients with low to intermediate-risk thyroid cancer. Pre-ablative Tg with cutoff value of 10.0 ng/mL is a promising factor to predict successful remnant ablation.

  19. Combined therapy with {sup 131}I and retinoic acid in Korean patients with radioiodine-refractory papillary thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oh, So Won [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University Boramae Medical Center, Department of Nuclear Medicine, Seoul (Korea, Republic of); Moon, Seung-hwan; Chung, June-Key [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Park, Do Joon; Cho, Bo Youn [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Jung, Kyeong Cheon [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Lee, Dong Soo [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University WCU Graduate School of Convergence Science and Technology, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul (Korea, Republic of)


    The aim of this study was to assess the clinical outcome of redifferentiation therapy using retinoic acid (RA) in combination with {sup 131}I therapy, and to identify biological parameters that predict therapeutic response in Korean patients with radioiodine-refractory papillary thyroid carcinoma (PTC). A total of 47 patients (13 men, 34 women; age 54.2 {+-} 13.6 years) with radioiodine-refractory PTC underwent therapy consisting of consecutive treatment with {sup 131}I and RA. Each {sup 131}I/RA treatment cycle involved the administration of oral isotretinoin for 6 weeks at 1-1.5 mg/kg daily followed by a single oral dose of {sup 131}I (range 5.5-16.7 GBq). Therapeutic responses were determined using serum thyroglobulin (Tg) levels and the change in tumour size 6 months after completing the {sup 131}I/RA therapy. Biological parameters and pathological parameters before and after combined therapy were compared. After completing {sup 131}I/RA therapy, 1 patient showed a complete response, 9 partial response, 9 stable disease, and 28 progressive disease, representing an overall response rate of 21.3%. Univariate analysis revealed that an age of <45 years and a persistently high serum Tg level were related to a good response. No clinical response was achieved when metastases showing no iodine uptake were present. Multivariate regression analysis showed that an age of <45 years was significantly associated with a good response. Of the 24 patients with well-differentiated carcinoma, 5 (20.8%) responded to {sup 131}I/RA therapy, whereas all 6 patients with poorly differentiated carcinoma failed to respond. {sup 131}I/RA therapy was found to elicit a response rate of 21.3% among patients with radioiodine-refractory PTC, and an age of <45 years was found to be significantly associated with a good response. (orig.)

  20. Clinical Usefulness between High Dose Radioiodine Therapy and Helicobacter Pylori Infection after Total Thyroidectomy due to Well Differentiated Thyroid Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Kuk No; Lim, Seok Tae; Moon, Eun Ha; Kim, Jin Suk; Jeong, Young Jin; Kim, Dong Wook; Jeong, Hwan Jeong; Sohn, Myung Hee [Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)


    Helicobacter (H) pylori infection has been considered the most important cause of gastritis, dyspepsia, and gastroduodenal ulcer. Radioiodine can be accumulated in the remaining thyroid tissue, salivary gland, and stomach. We investigated if the high radiation induced by radioiodine in the stomach after high dose radioiodine therapy (HD-RIT) is effective in the eradication of H. pylori infection. One hundred ninety nine patients (M:F=33:166, age 46.7{+-}12.3 years) who had HD-RIT (dose 159.1{+-}25.9 mCi, range 120-250 mCi) after thyroidectomy due to well differentiated thyroid cancer were enrolled. To detect H. pylori infection, the urea breath tests (UBT) were performed at 1 hour before HD-RIT and at 4 weeks after HD-RIT. The results of UBT were classified as positive ({>=}50 dpm) or negative (<50 dpm), and analyzed its values. Of 199 patients, 103 (51.8%) patients had positive UBT before HD-RIT. Of these, 80 patients had follow-up UBT after HD-RIT. Among them, 76 (95.0%) patients had persistent positive UBT and only 4 (5.0%) patients were changed negative UBT. Among 76 patients with persistent positive UBT, 26 (34.2%) patients had increased the values of follow-up UBT, 49 (64.5%) had decreased them, and 1 (1.3%) had shown the same value. The different values of UBT between before and after HD-RIT were 62{+-}66.1 dpm in increased one of follow-up UBT, and 153.3{+-}157.1 dpm in decreased one of follow-up UBT. We conclude that the radiation induced by HD-RIT is ineffective in the eradication of H. pylori infection. However, it could be influential the degree or distribution of H. pylori infection.

  1. Serum thyroxine and thyroid-stimulating hormone concentration in hyperthyroid cats that develop azotaemia after radioiodine therapy. (United States)

    Peterson, M E; Nichols, R; Rishniw, M


    The objectives of this study were to determine which serum thyroid hormone test best identifies iatrogenic hypothyroidism in cats that develop azotaemia after radioiodine treatment and to determine which thyroid test best differentiates these azotaemic, hypothyroid cats from azotaemic, radioiodine-treated euthyroid cats, as well as from azotaemic cats with chronic kidney disease and no history of thyroid disease. A total of 42 hyperthyroid cats that developed azotaemia (serum creatinine ê220 µmol/L) after radioiodine treatment had serum concentrations of thyroxine and free thyroxine by dialysis and thyroid--stimulating hormone measured at 3, 6 and 12 months. Iatrogenic hypothyroidism was confirmed (n=28) or excluded (n=14) on the basis of thyroid scintigraphy. A total of 14 cats with chronic kidney disease and 166 clinically normal cats underwent similar serum thyroid testing and scintigraphy. Concentrations of thyroxine and free thyroxine were lower and thyroid-stimulating hormone higher in hypothyroid cats than in all three groups of euthyroid cats (Pcats, thyroxine and free thyroxine concentrations were low in 15 (53·6%) and seven (25%), respectively. Low serum thyroxine and free thyroxine concentrations were also detected in seven (50%) and two (14·3%) of the cats with chronic kidney disease. Thyroid-stimulating hormone concentrations were elevated in all hypothyroid cats but remained within the reference interval in all three groups of euthyroid cats. Serum thyroid--stimulating hormone had a higher test sensitivity and specificity than either thyroxine or free thyroxine concentration. The finding of high serum thyroid-stimulating hormone concentrations best identifies feline iatrogenic hypothyroidism and differentiates it from non-thyroidal illness syndrome in cats that develop azotaemia after treatment. © 2017 British Small Animal Veterinary Association.

  2. Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine

    Directory of Open Access Journals (Sweden)

    Hutzen Brian


    Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus that encodes the human thyroidal sodium iodide symporter (NIS, has the potential to deliver targeted radiotherapy to the tumor site and promote a localized bystander effect above and beyond that achieved by MV alone. Methods We evaluated the efficacy of MV-NIS against medulloblastoma cells in vitro and examined their ability to incorporate radioiodine at various timepoints, finding peak uptake at 48 hours post infection. The effects of MV-NIS were also evaluated in mouse xenograft models of localized and disseminated medulloblastoma. Athymic nude mice were injected with D283med-Luc medulloblastoma cells in the caudate putamen (localized disease or right lateral ventricle (disseminated disease and subsequently treated with MV-NIS. Subsets of these mice were given a dose of 131I at 24, 48 or 72 hours later. Results MV-NIS treatment, both by itself and in combination with 131I, elicited tumor stabilization and regression in the treated mice and significantly extended their survival times. Mice given 131I were found to concentrate radioiodine at the site of their tumor implantations. In addition, mice with localized tumors that were given 131I either 24 or 48 hours after MV-NIS treatment exhibited a significant survival advantage over mice given MV-NIS alone. Conclusions These data suggest MV-NIS plus radioiodine may be a potentially useful therapy for

  3. Graves' disease and radioiodine therapy. Is success of ablation dependent on the achieved dose above 200 Gy?

    Energy Technology Data Exchange (ETDEWEB)

    Kobe, C.; Eschner, W.; Sudbrock, F.; Weber, I.; Marx, K.; Dietlein, M.; Schicha, H. [Dept. of Nuclear Medicine, Univ. of Cologne (Germany)


    Aim: this study was performed to determine the results of ablative radioiodine therapy (RIT) when the achieved dose in the thyroid was above 200 Gy and to characterize predictive factors for treatment outcome. Patients, methods: a total of 571 consecutive patients were observed for 12 months between July 2001 and June 2004. Inclusion criteria were a confirmed diagnosis Groves' disease, compensation of hyperthyroidism and withdrawal of antithyroid drugs two days before preliminary radioiodine-testing and RIT. The intended dose was 250 Gy and the therapeutically achieved dose was calculated from serial uptake measurements. The end-point measure was thyroid function 12 months after RIT; success was defined as elimination of hyperthyroidism. The relation between success rate and the achieved dose, thyroid volume, age and sex of patients, TSH- and TRAb-values and presence of ophthalmopathy was analysed. Results: relief from hyperthyroidism was achieved in 96% of patients who received more than 200 Gy, even for thyroid volumes >40 ml. The success of ablative RIT was not influenced by age or sex of patients, or by TSH- or TRAb values or concomitant ophthalmopathy. The mean achieved dose in the thyroid was 298 Gy with a standard deviation of 74.6 Gy. Conclusion: to achieve a dose of over 200 Gy with the above standard deviation, we recommend calculating on intended dose of 250 Gy and using a dosimetric approach with early and late uptake values in the radioiodine test, to allow early therapeutic intervention should the posttherapeutic thyroid dose fall unexpectedly below 200 Gy. (orig.)

  4. Accuracy and optimal timing of activity measurements in estimating the absorbed dose of radioiodine in the treatment of Graves' disease (United States)

    Merrill, S.; Horowitz, J.; Traino, A. C.; Chipkin, S. R.; Hollot, C. V.; Chait, Y.


    Calculation of the therapeutic activity of radioiodine 131I for individualized dosimetry in the treatment of Graves' disease requires an accurate estimate of the thyroid absorbed radiation dose based on a tracer activity administration of 131I. Common approaches (Marinelli-Quimby formula, MIRD algorithm) use, respectively, the effective half-life of radioiodine in the thyroid and the time-integrated activity. Many physicians perform one, two, or at most three tracer dose activity measurements at various times and calculate the required therapeutic activity by ad hoc methods. In this paper, we study the accuracy of estimates of four 'target variables': time-integrated activity coefficient, time of maximum activity, maximum activity, and effective half-life in the gland. Clinical data from 41 patients who underwent 131I therapy for Graves' disease at the University Hospital in Pisa, Italy, are used for analysis. The radioiodine kinetics are described using a nonlinear mixed-effects model. The distributions of the target variables in the patient population are characterized. Using minimum root mean squared error as the criterion, optimal 1-, 2-, and 3-point sampling schedules are determined for estimation of the target variables, and probabilistic bounds are given for the errors under the optimal times. An algorithm is developed for computing the optimal 1-, 2-, and 3-point sampling schedules for the target variables. This algorithm is implemented in a freely available software tool. Taking into consideration 131I effective half-life in the thyroid and measurement noise, the optimal 1-point time for time-integrated activity coefficient is a measurement 1 week following the tracer dose. Additional measurements give only a slight improvement in accuracy.

  5. Radioiodine therapy effects on offspring of patients with differentiated thyroid carcinoma; Efeitos da radioiodoterapia nas geracoes futuras de mulheres com carcinoma diferenciado de tireoide

    Energy Technology Data Exchange (ETDEWEB)

    Brandao, Carmen Dolores Goncalves [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil). Servico de Endocrinologia]. E-mail:; Antonucci, Jane [Instituto Nacional do Cancer, Rio de Janeiro, RJ (Brazil). Hospital das Clinicas. Servico de Medicina Nuclear; Correa, Nilson Duarte [Hospital dos Servidores do Estado, Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear; Corbo, Rossana; Vaisman, Mario [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina


    Radioiodine therapy has attained a significant role in the treatment of differentiated thyroid cancer. The literature addressing possible secondary effects of {sup 131} I is limited, although there has been increasingly interest in this field. A more comprehensive understanding of the mutagenic effects of radiation on the offspring of women exposed to {sup 131} I is mandatory in view of the possibility of occurrence of miscarriages, congenital abnormalities and malignancies in these children. In this review, we found that many reports on safety of this type of treatment in female patients in reproductive age recommend that pregnancy should be avoided for at least one year after therapeutic administration of radioiodine. (author)

  6. Determination of the optimal minimum radioiodine dose in patients with Graves' disease: a clinical outcome study

    Energy Technology Data Exchange (ETDEWEB)

    Howarth, D.; Tan, P.; Booker, J. [Pacific Medical Imaging, Newcastle, NSW (Australia); Epstein, M. [Dept. of Endocrinology, John Hunter Hospital, Newcastle, NSW (Australia); Lan, L. [High-Dependency Unit, St. George Hospital, Sydney, NSW (Australia)


    The study was performed under the auspices of the International Atomic Energy Commission, Vienna, Austria, with the aim of determining the optimal minimum therapeutic dose of iodine-131 for Graves' disease. The study was designed as a single-blinded randomised prospective outcome trial. Fifty-eight patients were enrolled, consisting of 50 females and 8 males aged from 17 to 75 years. Each patient was investigated by clinical assessment, biochemical and immunological assessment, thyroid ultrasound, technetium-99m thyroid scintigraphy and 24-h thyroid {sup 131}I uptake. Patients were then randomised into two treatment groups, one receiving 60 Gy and the other receiving 90 Gy thyroid tissue absorbed dose of radioiodine. The end-point markers were clinical and biochemical response to treatment. The median follow-up period was 37.5 months (range, 24-48 months). Among the 57 patients who completed final follow-up, a euthyroid state was achieved in 26 patients (46%), 27 patients (47%) were rendered hypothyroid and four patients (7%) remained hyperthyroid. Thirty-four patients (60%) remained hyperthyroid at 6 months after the initial radioiodine dose (median dose 126 MBq), and a total of 21 patients required additional radioiodine therapy (median total dose 640 MBq; range 370-1,485 MBq). At 6-month follow-up, of the 29 patients who received a thyroid tissue dose of 90 Gy, 17 (59%) remained hyperthyroid. By comparison, of the 28 patients who received a thyroid tissue dose of 60 Gy, 17 (61%) remained hyperthyroid. No significant difference in treatment response was found (P=0.881). At 6 months, five patients in the 90-Gy group were hypothyroid, compared to two patients in the 60-Gy group (P=0.246). Overall at 6 months, non-responders to low-dose therapy had a significantly larger thyroid gland mass (respective means: 35.9 ml vs 21.9 ml) and significantly higher levels of serum thyroglobulin (respective means: 597.6 {mu}g/l vs 96.9 {mu}g/l). Where low-dose radioiodine

  7. Prognostic factor analysis in 325 patients with Graves' disease treated with radioiodine therapy. (United States)

    Yang, Danrong; Xue, Jianjun; Ma, Wenxia; Liu, Furong; Fan, Yameng; Rong, Jie; Yang, Aimin; Yu, Yan


    I therapy is a choice for Graves' hyperthyroidism. Several factors that affect the success of I treatment in Graves' disease (GD) patients have been put forward. The aim of this retrospective study was to evaluate the factors influencing the success of I therapy and the occurrence of hypothyroidism after I therapy. We reviewed 325 GD patients, who were well documented out of 779 cases, treated with I in the First Affiliated Hospital of Xi'an Jiaotong University between 2010 and 2016. We collected the potential influencing factors, including demographic data (age, sex, family history), iodine intake state, antithyroid drugs (ATD) taking, thyroid texture, complications of hyperthyroidism, physical and laboratory examinations [thyroid weight, effective I half-life time (Teff), 24-h iodine uptake rate, tri-iodothyronine, thyroxine, free tri-iodothyronine (FT3), free thyroxine, thyroid-stimulating hormone, thyroglobulin antibody, thyroid microsome antibody, thyrotropin receptor antibody], and final administered dosages according to Quimby formula. The correlations between the prognosis of GD patients and these factors were analyzed by logistic regression analysis. Out of 325 patients, 247 (76.00%) were treated successfully with radioiodine. GD patients who were cured by I therapy were more likely to have smaller thyroid [odds ratio (OR)=0.988, 95% confidence interval (CI)=0.980-0.996, P=0.002], lower FT4 levels (OR=0.993, 95% CI=0.988-0.997, P=0.002), and shorter time of ATD withdrawal before I treatment (OR=0.985, 95% CI=0.975-0.996, P=0.002). Hypothyroidism occurred in 132 (41.00%) out of 325 patients. There was an increased risk of early hypothyroidism in patients with lower 24-h iodine uptake (OR=0.964, 95% CI=0.941-0.988, P=0.004), and treated with a lower total dose of iodine (OR=0.892, 95% CI=0.824-0.965, P=0.005) and a higher iodine dose per garm of thyroid tissue (OR=5.414E+14, 95% CI=45.495-6.444E+27, P=0.027). Our results showed that I treatment was more

  8. Radioiodine (1-131) Dose for the Treatment of Hyperthyroidism in Rajavithi Hospital. (United States)

    Kuanrakcharoen, Pichit


    The main cause of hyperthyroidism is diffuse toxic goiter (Graves' disease), and the treatment of choice after medical therapy failure is radioiodine (I-131). There are two common methods of determining the optimal I-131 dose: calculated dose or fixed dose. The calculated dose method is based on the following formula: 75-200 microcuri/gram of thyroid gland divided by the percentage of radioiodine uptake at 24 hours (24-hour RAIU). As this is quite complex, some centers use fixed doses, such as 5, 10 or 15 mCi because it is simpler. At Rajavithi Hospital, the applied dose of I-131 is determined based on the thyroid gland weight assessed by palpation and other clinical factors. To study the mean I-131 dose for the initial treatment of hyperthyroidism in Rajavithi Hospital, to find the clinical factors that correlate with I-131 treatment dose, and to devise a formula to predict the optimal I-131 treatment dose. This was a retrospective study of 510 patients with a diagnosis of hyperthyroidism who received initial I-131 treatment at the Department of Nuclear Medicine in Rajavithi Hospital between January 2014 and June 2015. Baseline characteristics including age, sex, age at diagnosis, duration of antithyroid drug (ATD) therapy, gland weight (g), 3-hour RAIU and I-131 treatment dose were reviewed from medical records. The mean age ± SD was 41.93 ± 14.11 years (range 14-81 years), and the male to female ratio was 4.1:1. The mean duration of ATD therapy was 3.54 ± 4.02 years (min-max, 0.8-40.6 years). The mean gland weight was 54.35 ± 32.95 grams, and the mean 3-hour RAIU was 55.5 ± 23.69%. The mean I-131 treatment dose was 14.84 ± 5.71 mCi (min-max, 7-30 mCi). There was no significant correlation between dose and age, age at diagnosis, duration of A TD therapy or 3-hour RAIU. The study showed a significant correlation between I-131 dose and gland size, r = 0.938 (p hyperthyroidism after medical therapy failure, and there are various techniques for determining the

  9. What is the best pre-therapeutic dosimetry for successful radioiodine therapy of multifocal autonomy?

    Energy Technology Data Exchange (ETDEWEB)

    Gotthardt, M. [Radboud Univ. Nijmegen Medical Center, Nijmegen (Netherlands). Dept. of Nuclear Medicine; Philipps Univ., Marburg (Germany). Dept. of Nuclear Medicine; Rubner, C. [Philipps Univ., Marburg (Germany). Dept. of Nuclear Medicine; Bauhofer, A. [Philipps Univ., Marburg (DE). Inst. of Theoretical Surgery] (and others)


    Purpose: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies (MFA) is a problem as therapeutic outcome may be worse than in other kinds of autonomies. We compared different dosimetric concepts in our patients. Patients, methods: Data from 187 patients who had undergone RIT for MFA (Marinelli algorithm, volumetric compromise) were included in the study. For calculation, either a standard or a measured half-life had been used and the dosimetric compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated by 2 alternative concepts and compared to therapeutic success achieved (concept of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based adaptation of target dose on total thyroid volume). Results: If a standard half-life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n=143). If a measured half-life was used the success rate was 93.1% (13,6% hypothyroidism, n=44). These differences were statistically not significant, neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid after therapy (ANOVA, all p>0.05). The alternative dosimetric concepts would have resulted either in significantly lower organ doses (TcTUs-based calculation of autonomous volume; 80.76{+-}80.6 Gy versus 125.6{+-}46.3 Gy; p<0.0001) or in systematic over-treatment with significantly higher doses (TcTUs-adapted concept; 164.2{+-}101.7 Gy versus 125.6{+-}46.3 Gy; p=0.0097). Conclusions: TcTUs-based determination of the autonomous volume should not be performed, the TcTUs-based adaptation of the target dose will only increase the rate of hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for RIT of MFA. If so, individual therapeutic activities may be calculated based on thyroid size corrected to the 24h ITUs without using Marinelli's algorithm. (orig.)

  10. (/sup 125/I) radioiodinated metaraminol: A new platelet-specific labeling agent

    Energy Technology Data Exchange (ETDEWEB)

    Ohmomo, Y.; Yokoyama, A.; Kawai, K.; Arano, Y.; Horiuchi, K.; Tanaka, C.; Saji, H.; Torizuka, K.


    In our search for a platelet-specific labeling agent, metaraminol (MA), a low-toxic pharmaceutical for the treatment of hypotension and cardiogenic shock, attracted our attention. Its active incorporation and accumulation by platelets have been recognized. At first, the preparation of /sup 125/I radioiodinated metaraminol (/sup 125/I-MA) was carried out using the chloramine-T method. Then, upon the harvest of platelets as platelet-rich plasma (PRP), their labeling with this new radiopharmaceutical was easily performed by incubation for 10 min at 37/sup 0/C. The cell-labeling efficiency was dependent on cell density, reaching 63.0%+-3.1% at 2.4x10/sup 9/ cells/ml. The specific incorporation of /sup 125/I-MA by an active transport system similar to that of 5-hydroxytryptamine (5-HT) as well as by passive diffusion was demonstrated. In vitro studies, the unaltered state of /sup 125/I-MA-labeled platelets with their cellular functions fully retained was estimated. In vivo studies carried out in rabbits with induced thrombi in the femoral artery showed a rather rapid disappearance of the radioactivity from circulating blood, reaching a high thrombus-to-blood activity ratio of 19.8+-4.3 within 30 min of the administration of /sup 125/I-MA-labeled autologous platelets. Thus, with the potential availability of /sup 123/I, /sup 123/I-MA-labeled platelets appear to be a promising agent for thrombus imaging using single-emission computed tomography (CT) studies.

  11. Should radioiodine be the first-line treatment for paediatric Graves' disease? (United States)

    West, James D; Cheetham, Timothy D; Dane, Carole; Natarajan, Anuja


    Debate exists regarding the optimal treatment strategy for paediatric Graves' disease with radioiodine (RAI), and surgery, usually reserved for failure of medical therapy. We present our own experience to introduce a review of the published literature focussing on the predictors of remission after antithyroid drug (ATD) therapy from diagnosis, and discuss whether RAI should be considered as a first-line therapy. A retrospective analysis of all diagnosed cases of paediatric Graves' disease presenting to a large District General Hospital. Thirteen patients were diagnosed with Graves' disease between February 2004 and May 2013. The median age at diagnosis was 13.7 years (range 7.2-17.1 years) with a female:male ratio of 11:2. Some nine patients completed a 2-year course of carbimazole out of which 8 relapsed after a mean duration of 0.82 years (range 0.08-1.42 years); the ninth currently remains in remission. Of the eight patients who relapsed, three have undergone RAI treatment. Two patients failed to tolerate carbimazole treatment, one of whom received RAI treatment because surgery was contraindicated and one patient with severe autism proceeded to RAI treatment due to poor compliance and persistent hyperthyroidism. Prognostic factors at presentation predicting a low likelihood of remission following ATD treatment include younger age, non-Caucasian ethnicity, and severe clinical and/or biochemical markers of hyperthyroidism. Psycho-social factors including compliance also influence management decisions. In specifically selected patients presenting with paediatric Graves' disease, the benefits and risks of radioactive iodine as a potential first-line therapy should be communicated allowing families to make informed decisions.

  12. Thymic Involution After Radioiodine Therapy for Graves Disease: Relationships With Serum Thyroid Hormones and TRAb. (United States)

    Jinguji, Megumi; Nakajo, Masayuki; Nakajo, Masatoyo; Koriyama, Chihaya; Yoshiura, Takashi


    The mechanisms of thymic hyperplasia in Graves disease and its involution after radioiodine (I-131) therapy remain unknown. To examine whether computed tomography (CT) findings of the thymus in patients with Graves disease change before and 6 months after I-131 therapy and to elucidate factors that affect these changes. A retrospective, single-center study was conducted. Thymic and thyroid volumes and thymic density were measured on CT. The associations of thymic volume or density with the following factors before I-131 therapy were examined: age; serum triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone receptor antibody (TRAb) levels; and thyroid volume. The changes in thymic volume and density and TRAb levels before and after I-131 therapy, and the correlations of thymic volume with T3 and T4 decline rates and TRAb changing rate and age were examined. We studied 40 consecutive patients with Graves disease who underwent neck and chest CT before and 6 months after I-131 therapy. Observational study. A significant negative correlation was observed only between thymic density and age before I-131 therapy. Thymic volume and density decreased and TRAb levels increased significantly after I-131 therapy. The thymic volume decline rate significantly positively correlated with serum T3 and thyroid volume decline rates. No significant correlation was found between thymic volume decline and TRAb changing rates. Significant thymic involution occurs after I-131 therapy in patients with Graves disease. Serum T3, but not TRAb, may be related to thymic hyperplasia and involution following I-131 therapy.

  13. Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine

    Energy Technology Data Exchange (ETDEWEB)

    Pacini, F.; Gasperi, M.; Fugazzola, L. [Univ. of Pisa (Italy)] [and others


    The aim of the present study was to assess whether {sup 131}I therapy for differentiated thyroid carcinoma (DTC) can affect endocrine testicular function. Serum follicle-stimulating hormone (FSH) and testosterone (T) concentrations were measured in 103 patients periodically submitted for radioiodine therapy for residual or metastatic disease. Mean follow-up was 93.7{+-}54 mo (range 10-243 mo). Mean FSH values in {sup 131}I-treated patients tested after their last treatment were 15.3{+-}9.9 mU/ml, significantly higher than those of 19 untreated patients (6.5{+-}3.1 mU/ml). Considering the mean +3 s.d. FSH of untreated subjects as the upper limit of normal range, 36.8% of the patients had an abnormal increase in serum FSH. Longitudinal analysis performed in 21 patients showed that the behavior of FSH in response to {sup 131}I therapy was not universal. Six patients had no change or a slight increase in serum FSH after {sup 131}I administration; eleven patients had a transient increase above normal values 6-12 mo after {sup 131}I treatment, with return to normal levels in subsequent months. The administration of a second dose was followed by a similar increase in FSH levels. Finally, four patients, followed for a long period of time and treated with several {sup 131}I doses, showed a progressive increase in serum FSH, which eventually became permanent. Semen analysis, performed in a small subgroup of patients, showed a consistent reduction in the number of normokinetic sperm. No change was found in serum T levels between treated and untreated patients. The results indicate that {sup 131}I therapy for thyroid carcinoma is associated with transient impairment of testicular germinal cell function. The damage may become permanent for high-radiation activities delivered year after year and might pose a significant risk of infertility. 14 refs., 8 figs., 1 tab.

  14. Combined Cerenkov luminescence and nuclear imaging of radioiodine in the thyroid gland and thyroid cancer cells expressing sodium iodide symporter: initial feasibility study. (United States)

    Jeong, Shin Young; Hwang, Mi-Hye; Kim, Jung Eun; Kang, Sungmin; Park, Jeong Chan; Yoo, Jeongsoo; Ha, Jeoung-Hee; Lee, Sang-Woo; Ahn, Byeong-Cheol; Lee, Jaetae


    Radioiodine (RI) such as (131)I or (124)I, can generate luminescent emission and be detected with an optical imaging (OI) device. To evaluate the possibility of a novel Cerenkov luminescence imaging (CLI) for application in thyroid research, we performed feasibility studies of CLI by RI in the thyroid gland and human anaplastic thyroid carcinoma cells expressing sodium iodide symporter gene (ARO-NIS). For in vitro study, FRTL-5 and ARO-NIS were incubated with RI, and the luminometric and CLI intensity was measured with luminometer and OI device. Luminescence intensity was compared with the radioactivity measured with γ-counter. In vivo CLI of the thyroid gland was performed in mice after intravenous injection of RI with and without thyroid blocking. Mice were implanted with ARO-NIS subcutaneously, and CLI was performed with injection of (124)I. Small animal PET or γ-camera imaging was also performed. CLI intensities of thyroid gland and ARO-NIS were quantified, and compared with the radioactivities measured from nuclear images (NI). Luminometric assay and OI confirmed RI uptake in the cells in a dose-dependent manner, and luminescence intensity was well correlated with radioactivity of the cells. CLI clearly demonstrated RI uptake in thyroid gland and xenografted ARO-NIS cells in mice, which was further confirmed by NI. A strong positive correlation was observed between CLI intensity and radioactivity assessed by NI. We successfully demonstrated dual molecular imaging of CLI and NI using RI both in vitro and in vivo. CLI can provide a new OI strategy in preclinical thyroid studies. ©The Japan Endocrine Society

  15. Metastatic Follicular Thyroid Carcinoma Secreting Thyroid Hormone and Radioiodine Avid without Stimulation: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Syed A. Abid


    Full Text Available Introduction. This is an extremely rare case of a patient with metastatic follicular thyroid cancer who continued to produce thyroid hormone and was iodine scan positive without stimulation after thyroidectomy and radioiodine (I-131 therapy. Patient Findings. A 76-year-old Caucasian male was diagnosed with metastatic follicular thyroid carcinoma on lung nodule biopsy. Total thyroidectomy was performed and he was ablated with 160 mCi of I-131 after recombinant human thyrotropin (rhTSH stimulation. Whole body scan (WBS after treatment showed uptake in bilateral lungs, right sacrum, and pelvis. The thyroglobulin decreased from 2,063 to 965 four months after treatment but rapidly increased to 2,506 eleven months after I-131. Thyroid stimulating hormone (TSH remained suppressed and free T4 remained elevated after I-131 therapy without thyroid hormone supplementation. He was treated with an additional 209 mCi with WBS findings positive in lung and pelvis. Despite I-131, new metastatic lesions were noted in the left thyroid bed and large destructive lesion to the first cervical vertebrae four months after the second I-131 dose. Conclusions. This case is exceptional because of its rarity and also due to the dissociation between tumor differentiation and aggressiveness. The metastatic lesions continued to secrete thyroid hormone and remained radioiodine avid with rapid progression after I-131 therapy.

  16. Serum thyroxine and age - rather than thyroid volume and serum TSH - are determinants of the thyroid radioiodine uptake in patients with nodular goiter

    DEFF Research Database (Denmark)

    Bonnema, S J; Fast, S; Nielsen, V E


    Background: 131I therapy is widely used for treatment of non-toxic goiters. A limitation for this treatment is a low thyroid radioiodine uptake (RAIU), often encountered in these patients. Aim: To estimate the impact of various factors on the thyroid RAIU. Methods: We examined prospectively 170 p...

  17. Post-surgical use of radioiodine (I-131) in patients with papillary and follicular thyroid cancer and the issue of remnant ablation : A consensus report

    NARCIS (Netherlands)

    Pacini, F; Schlumberger, M; Harmer, C; Berg, GG; Cohen, O; Duntas, L; Jamar, F; Jarzab, B; Limbert, E; Lind, P; Reiners, C; Franco, FS; Smit, J; Wiersinga, W

    Objective: To determine, based on published literature and expert clinical experience. current indications for the post-surgical administration of a large radioiodine activity in patients with differentiated thyroid cancer. Design and methods: A literature review was performed and was then analyzed

  18. Long-term analysis of the efficacy and tolerability of sorafenib in advanced radio-iodine refractory differentiated thyroid carcinoma: final results of a phase II trial

    NARCIS (Netherlands)

    Schneider, T.C.; Abdulrahman, R.M.; Corssmit, E.P.; Morreau, H.; Smit, J.W.A.; Kapiteijn, E.


    OBJECTIVE: We conducted a prospective phase II clinical trial to determine the efficacy of sorafenib in patients with advanced radio-iodine refractory differentiated thyroid cancer. In this article, the long-term results are presented. PATIENTS AND METHODS: Thirty-one patients with progressive

  19. Post-surgical use of radioiodine (I-131) in patients with papillary and follicular thyroid cancer and the issue of remnant ablation : A consensus report

    NARCIS (Netherlands)

    Pacini, F; Schlumberger, M; Harmer, C; Berg, GG; Cohen, O; Duntas, L; Jamar, F; Jarzab, B; Limbert, E; Lind, P; Reiners, C; Franco, FS; Smit, J; Wiersinga, W


    Objective: To determine, based on published literature and expert clinical experience. current indications for the post-surgical administration of a large radioiodine activity in patients with differentiated thyroid cancer. Design and methods: A literature review was performed and was then analyzed

  20. Post-surgical use of radioiodine (131I) in patients with papillary and follicular thyroid cancer and the issue of remnant ablation: a consensus report

    NARCIS (Netherlands)

    Pacini, Furio; Schlumberger, Martin; Harmer, Clive; Berg, Gertrud G.; Cohen, Ohad; Duntas, Leonidas; Jamar, François; Jarzab, Barbara; Limbert, Eduard; Lind, Peter; Reiners, Cristoph; Sanchez Franco, Franco; Smit, Johannes; Wiersinga, Wilmar


    To determine, based on published literature and expert clinical experience, current indications for the post-surgical administration of a large radioiodine activity in patients with differentiated thyroid cancer. A literature review was performed and was then analyzed and discussed by a panel of

  1. Synthesis and evaluation of radioiodinated cyclooxygenase-2 inhibitors as potential SPECT tracers for cyclooxygenase-2 expression

    Energy Technology Data Exchange (ETDEWEB)

    Kuge, Yuji [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)]. E-mail:; Katada, Yumiko [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Shimonaka, Sayaka [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Temma, Takashi [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Kimura, Hiroyuki [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Kiyono, Yasushi [Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Yokota, Chiaki [Cerebrovascular Laboratory, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Minematsu, Kazuo [Cerebrovascular Division, Department of Medicine, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Seki, Koh-ichi [Central Institute of Isotope Science, Hokkaido University, Hokkaido 060-8638 (Japan); Tamaki, Nagara [Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Hokkaido 060-8638 (Japan); Ohkura, Kazue [Department of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido 061-0293 (Japan); Saji, Hideo [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)


    Although several COX-2 inhibitors have recently been radiolabeled, their potential for imaging COX-2 expression remains unclear. In particular, the sulfonamide moiety of COX-2 inhibitors may cause slow blood clearance of the radiotracer, due to its affinity for carbonic anhydrase (Canada) in erythrocytes. Thus, we designed a methyl sulfone-type analogue, 5-(4-iodophenyl)-1-[4-(methylsulfonyl)phenyl]-3-trifluoromethyl-1H-pyrazole (IMTP). In this study, the potential of radioiodinated IMTP was assessed in comparison with a {sup 125}I-labeled celecoxib analogue with a sulfonamide moiety ({sup 125}I-IATP). Methods: The COX inhibitory potency was assessed by measuring COX-catalyzed oxidation by hydrogen peroxide. The biodistribution of {sup 125}I-IMTP and {sup 125}I-IATP was determined by the ex vivo tissue counting method in rats. Distribution of the labeled compounds to rat blood cells was measured. Results: The COX-2 inhibitory potency of IMTP (IC{sub 5}=5.16 {mu}M) and IATP (IC{sub 5}=8.20 {mu}M) was higher than that of meloxicam (IC{sub 5}=29.0 {mu}M) and comparable to that of SC-58125 (IC{sub 5}=1.36 {mu}M). The IC{sub 5} ratios (COX-1/COX-2) indicated the high isoform selectivity of IMTP and IATP for COX-2. Significant levels of {sup 125}I-IMTP and {sup 125}I-IATP were observed in the kidneys and the brain (organs known to express COX-2). The blood clearance of {sup 125}I-IMTP was much faster than that of {sup 125}I-IATP. Distribution of {sup 125}I-IATP to blood cells (88.0%) was markedly higher than that of {sup 125}I-IMTP (18.1%), which was decreased by CA inhibitors. Conclusions: Our results showed a high inhibitory potency and selectivity of IMTP for COX-2. The substitution of a sulfonamide moiety to a methyl sulfone moiety effectively improved the blood clearance of the compound, indicating the loss of the cross reactivity with CA in {sup 125}I-IMTP. {sup 123}I-IMTP may be a potential SPECT radiopharmaceutical for COX-2 expression.

  2. The utility of I-123 pretherapy scan in I-131 radioiodine therapy for thyroid cancer. (United States)

    Chen, Ming-Kai; Yasrebi, Mona; Samii, Jason; Staib, Lawrence H; Doddamane, Indukala; Cheng, David W


    There is a growing belief that a pretherapy scan yields little or no additional information that would impact on radioiodine ablation dosing. In addition, there is some concern regarding on the stunning effect of a pretherapy scan, especially when I-131 radioisotope is used for imaging. We hypothesized that a pretherapy scan provides invaluable information on the amount of thyroid remnant, sometimes indicating the need for two-step I-131 ablation. It may also detect unsuspected local lymph node involvement or distant metastases, indicating the requirement for a higher I-131 dose after thyroidectomy. The aim of this study was to evaluate how effective pretherapy scans are for guiding I-131 therapy planning and augmenting information provided in the pathology reports for thyroidectomy specimens. We reviewed 122 patients who underwent I-123 pretherapy scan and I-131 radioablation at Yale New Haven Hospital between January 2006 and August 2007. The percentage of neck uptake and whole-body images were acquired 24 hours following the administration of 51.8 MBq (1.4 mCi) of I-123 NaI. A 24-hour uptake of >3% was used as the cutoff to determine whether there was a greater than desired quantity of thyroid remnant, which would require a two-step treatment protocol. Furthermore, attention was paid to identifying cervical lymph nodes, which may not have presented themselves in the euthyroid state at the time of thyroidectomy. Additional clinical information provided by pretherapy scans was computed as percentages with 95% confidence intervals by using adjusted Wald intervals. Overall, the pretherapy scans provided additional critical information in 25% of the cases (31/122; 95% CI: 18%-34%). For cases demonstrating >3% uptake with midline lymph nodes, the pretherapy scan provided additional information in 50% of the cases (8/16; 95% CI: 28%-72%). Our study demonstrated that I-123 pretherapy scans provide valuable information with regard to unsuspected lymph nodes or

  3. Gene (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  4. Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression

    Energy Technology Data Exchange (ETDEWEB)

    Li, Luchuan; Lv, Bin; Chen, Bo [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Guan, Ming [Department of General Surgery, Qihe People' s Hospital, Qihe, Shandong 251100 (China); Sun, Yongfeng [Department of General Surgery, Licheng District People' s Hospital, Jinan, Shandong 250115 (China); Li, Haipeng [Department of General Surgery, Caoxian People' s Hospital, Caoxian, Shandong 274400 (China); Zhang, Binbin; Ding, Changyuan; He, Shan [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Zeng, Qingdong, E-mail: [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China)


    Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, was picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na{sup +}/I{sup −} symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC). - Highlights: • Significant upregulated miR-146b was picked up from thyroid relative miRNAs in DTC. • MiR-146b was negatively regulated by HDAC3 in normal thyroid carcinoma cells. • NIS activity and expression could be regulated by miR-146b in thyroid carcinoma. • MiR-146b inhibition could recover the decreased radioiodine-sensitivity of DTC cells.

  5. 99mTc-EDDA/HYNIC-TOC in the diagnosis of differentiated thyroid carcinoma refractory to radioiodine treatment. (United States)

    Czepczyński, Rafał; Gryczyńska, Maria; Ruchała, Marek


    In majority of cases of differentiated thyroid carcinoma (DTC), the ablative radioiodine treatment shows high efficacy. In a small number of patients, mechanism of selective iodine uptake by the DTC cells is insufficient and alternative methods of diagnosis and treatment are needed. As demonstrated in vitro, DTC cells show expression of somatostatin recep-tors. Radiolabeled somatostatin analogs are widely used in the diagnosis of neuroendocrine tumors. The aim of the study was to evaluate the utility of peptide receptor scintigraphy with the use of 99mTc-EDDA/HYNIC-TOC in the diagnosis of DTC in patients with elevated thyroglobulin concentrations (Tg), negative WBS and no effect of the consecutive radioiodine therapies. Whole body scintigraphy as well as SPECT of neck and chest were performed 3 and 24 h after i.v. administration of 740 MBq 99mTc-EDDA/HYNIC-TOC. The obtained images were compared with other radionuclide and ra-diological imaging methods. Forty-three patients with DTC after surgery and ablative radioiodine treatment with negative WBS and elevated Tg were qualified. Patients' age: 18-83 years (mean 58.0). SRS showed foci of tracer accumulation in 29 cases (67.4%). Sensitivity was 69.0% specificity 78.6%. SRS correctly identified local recurrence in 8 pts., metastatic lymph nodes in 19 pts., lung metastases in 12 pts. and bone metastases in 5 pts. SRS showed high sensitivity in the detection of metastatic lymph nodes (100%) and bone metastases (83.3%) and lung metastases (63.2%). Positive SRS was found in pts. with higher Tg concentrations (130 ± 144 vs. 30 ± 54 ng/ml). Scintigraphy with the use of the studied technetium-99m-labeled somatostatin analog is useful in the evaluation of patients with advanced DTC. It shows relatively good sensitivity and specificity but not high enough to be recommended as a routine imaging method. The role of somatostatin receptor scintigraphy in DTC is complementary to other imaging modalities.

  6. Recombinant human thyrotropin-stimulated radioiodine therapy of nodular goiter allows major reduction of the radiation burden with retained efficacy

    DEFF Research Database (Denmark)

    Fast, Søren; Hegedüs, Laszlo; Grupe, Peter


    Context and Objective: Stimulation with recombinant human TSH (rhTSH) before radioiodine ((131)I) therapy augments goiter volume reduction (GVR). Observations indicate that rhTSH has a preconditioning effect beyond increasing thyroid (131)I uptake. We test the hypothesis that an equivalent GVR......-3530) in the placebo group (70% reduction, P radiation regulation, hospitalization was required in 14 patients in the placebo group vs. one patient in the rhTSH group (P .... The prevalence of myxedema (10%) did not differ among groups. Conclusions: This is the first study to demonstrate that rhTSH not only increases the thyroid (131)I uptake, but per se potentiates the effect of (131)I-therapy, allowing a major reduction of the (131)I-activity without compromising efficacy...

  7. An optimization study for radioiodination of a new synthesized benzamide derivative as an analogue tracer for malignant melanoma imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kandil, Shaban A.; Aglan, Hany; Seddik, Usama [Atomic Energy Authority, Cairo (Egypt). Nuclear Research Center; EL-Kafrawy, Ahmed F. [Ain Shams Univ., Cairo (Egypt). Faculty of Science


    Iodobenzamides are reported to possess some affinity for melanoma. This study describes the synthesis of a new benzamide analogue, N-(2-diethylamino-ethyl)-4-(4-chloro-nicotinamido)-5-[{sup 125}I]iodo-2 -methoxybenz amide ([{sup 125}I]H4) designed to target melanoma. The synthesis was simply achieved in four steps. There were two PyCIU/DIPEA amide condensations and a transfer hydrogenation using an ammonium formate hydrogen donor. The radioiodination step was carried out with {sup 125}I via an electrophilic substitution reaction. The reaction conditions were optimized. The labeled compound was purified by HPLC. The maximum radiochemical yield was found to be 78% at a radiochemical purity of 98%. All compounds were characterized by MS and NMR techniques. The log P value for [{sup 125}I]H4 was found as 3.96±0.5.

  8. Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

    Energy Technology Data Exchange (ETDEWEB)

    Willegaignon, J., E-mail:; Sapienza, M. T.; Coura-Filho, G. B.; Buchpiguel, C. A. [Cancer Institute of São Paulo State (ICESP), Clinical Hospital, School of Medicine, University of São Paulo, São Paulo 01246-000 (Brazil); Nuclear Medicine Service, Department of Radiology, School of Medicine, University of São Paulo, Sao Paulo 01246-000 (Brazil); Watanabe, T. [Nuclear Medicine Service, Department of Radiology, School of Medicine, University of São Paulo, São Paulo 01246-000 (Brazil); Traino, A. C. [Unit of Medical Physics, Azienda Ospedaliero-Universitaria Pisana, Pisa 56126 (Italy)


    Purpose: The precise determination of organ mass (m{sub th}) and total number of disintegrations within the thyroid gland (A{sup ~}) are essential for thyroid absorbed-dose calculations for radioiodine therapy. Nevertheless, these parameters may vary according to the method employed for their estimation, thus introducing uncertainty in the estimated thyroid absorbed dose and in any dose–response relationship derived using such estimates. In consideration of these points, thyroid absorbed doses for Graves’ disease (GD) treatment planning were calculated using different approaches to estimating the m{sub th} and the A{sup ~}. Methods: Fifty patients were included in the study. Thyroid{sup 131}I uptake measurements were performed at 2, 6, 24, 48, 96, and 220 h postadministration of a tracer activity in order to estimate the effective half-time (T{sub eff}) of {sup 131}I in the thyroid; the thyroid cumulated activity was then estimated using the T{sub eff} thus determined or, alternatively, calculated by numeric integration of the measured time-activity data. Thyroid mass was estimated by ultrasonography (USG) and scintigraphy (SCTG). Absorbed doses were calculated with the OLINDA/EXM software. The relationships between thyroid absorbed dose and therapy response were evaluated at 3 months and 1 year after therapy. Results: The average ratio (±1 standard deviation) betweenm{sub th} estimated by SCTG and USG was 1.74 (±0.64) and that between A{sup ~} obtained by T{sub eff} and the integration of measured activity in the gland was 1.71 (±0.14). These differences affect the calculated absorbed dose. Overall, therapeutic success, corresponding to induction of durable hypothyroidism or euthyroidism, was achieved in 72% of all patients at 3 months and in 90% at 1 year. A therapeutic success rate of at least 95% was found in the group of patients receiving doses of 200 Gy (p = 0.0483) and 330 Gy (p = 0.0131) when m{sub th} was measured by either USG or SCTG and A

  9. Comparison of radioiodine biokinetics following the administration of recombinant human thyroid stimulating hormone and after thyroid hormone withdrawal in thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Luster, Markus; Lassmann, Michael; Haenscheid, Heribert; Reiners, Christoph [Department of Nuclear Medicine, University of Wuerzburg, Josef-Schneider-Strasse 2, 97080, Wuerzburg (Germany); Sherman, Steven I. [Section of Endocrine Neoplasia and Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, Houston, Texas (United States); Skarulis, Monica C. [Division of Intramural Research, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland (United States); Reynolds, James R. [Department of Nuclear Medicine, Warren Grant Magnusen Clinical Center, NIH, Bethesda, Maryland (United States)


    Iodine kinetics were studied in patients with differentiated thyroid cancer while euthyroid under exogenous thyroid stimulating hormone (TSH) and while hypothyroid to detect differences in radioiodine uptake, distribution and elimination. Nine patients with total or near-total thyroidectomy on thyroid hormone suppressive therapy received two or three daily doses of 0.9 mg recombinant human TSH (rhTSH) followed by administration of a diagnostic activity of 2 mCi (74 MBq) iodine-131. After the biokinetics assessments had been performed, patients stopped taking thyroid hormones to become hypothyroid. A second 2 mCi (74 MBq) diagnostic activity of {sup 131}I was administered, followed by a second set of biokinetics assessments. One week later the patients underwent remnant ablation with a therapeutic activity of {sup 131}I. A comparison of the {sup 131}I kinetics in the patients while euthyroid and while hypothyroid showed major differences in the doses to the remnant as well as in residence times and radiation exposure to the blood. In the first diagnostic assessment the remnant dose was higher in eight of the nine patients and clearance of the activity from the blood was faster in all of them. The data from this study suggest that radioiodine administration is potent and safe when administered to euthyroid patients following rhTSH administration. Enhanced residence time in the remnant and decreased radiation exposure to the blood were noted when patients were euthyroid compared to when they were rendered hypothyroid. However, all patients received diagnostic activities in the same order: first while euthyroid, followed by hypothyroidism. It is quite possible that ''stunning'' from the radioiodine administered in the initial uptake study inhibited the subsequent uptake of radioiodine by the remnant lesions in the second uptake study. (orig.)

  10. Is There a Role for Unstimulated Thyroglobulin Velocity in Predicting Recurrence in Papillary Thyroid Carcinoma Patients with Detectable Thyroglobulin after Radioiodine Ablation?


    Wong, Hilda; Wong, Kai P.; Yau, Thomas; Tang, Vikki; Leung, Roland; Chiu, Joanne; Lang, Brian Hung-Hin


    Background In the follow-up of papillary thyroid cancer (PTC) patients treated with curative thyroidectomy and radioiodine ablation, raised thyroglobulin (Tg) predicts recurrence with reasonable sensitivity and specificity. However, a proportion of patients present with raised Tg level but no other clinical evidence of disease. Only limited data on Tg kinetics have been reported to date. Here we aim to evaluate the prognostic and predictive significance of nonstimulated serum Tg velocity (TgV...

  11. Fibroelastic pseudotumor elastofibroma dorsi detected by 18F-FDG PET/CT scan and by postherapy radioiodine SPECT/CT. (United States)

    Oporto, M; Cepa, F; Orta, N; Rubí, S; Navalón, H; Peña, C

    Radioiodine uptake in the thyroid tissue, metastasis of differentiated thyroid cancer (DTC), and in other tissues, depends on the expression of sodium-iodide symporter (NIS). Vascular permeability, effusions, inflammation, and other mechanisms may also play a role in the accumulation of radioactive iodine. A 63-year-old woman underwent radioiodine therapy, as well as a post-therapy whole-body scan, as she was suspected of having lung metastasis from thyroid carcinoma. The scan not only showed uptake at the lung metastasis but also a faint diffuse bilateral uptake in the posterior thorax. On SPECT/CT this uptake was located in a known Elastofibroma Dorsi (ED) previously diagnosed by contrast CT and viewed in a FDG PET/CT. The radioiodine uptake in ED, especially if typical, is not a diagnostic problem in SPECT/CT study, but can be misleading in a study limited to a few planar images, particularly if the uptake occurs asymmetrically, or ED is located in a unsuspected area. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  12. Calculations of S values and effective dose for the radioiodine carrier and surrounding individuals based on Chinese hybrid reference phantoms using the Monte Carlo technique. (United States)

    Geng, Changran; Tang, Xiaobin; Qian, Wei; Guan, Fada; Johns, Jesse; Yu, Haiyan; Gong, Chunhui; Shu, Diyun; Chen, Da


    The S values for the thyroid as the radioiodine source organ to other target organs were investigated using Chinese hybrid reference phantoms and the Monte Carlo code MCNP5. Two radioiodine isotopes (125)I and (131)I uniformly distributed in the thyroid were investigated separately. We compared our S values for (131)I in Chinese phantoms with previous studies using other types of phantoms: Oak Ridge National Laboratory (ORNL) stylized phantoms, International Commission on Radiological Protection (ICRP) voxel phantoms, and University of Florida (UF) phantoms. Our results are much closer to the UF phantoms. For each specific target organ, the S value for (131)I is larger than for (125)I in both male and female phantoms. In addition, the S values and effective dose to surrounding face-to-face exposed individuals, including different genders and ages (10- and 15-year-old juniors, and adults) from an adult male radioiodine carrier were also investigated. The target organ S values and effective dose for surrounding individuals obey the inverse square law with the distance between source and target phantoms. The obtained effective dose data in Chinese phantoms are comparable to the results in a previous study using the UF phantoms. The data generated in this study can serve as the reference to make recommendations for radiation protection of the Chinese patients or nuclear workers.

  13. THYRPAN-TM Prototype: New System for Online Telemonitoring of Patients with Thyroid Carcinoma During the Treatment with a High Dose of Radioiodine. (United States)

    Matovic, Milovan D; Jeremic, Marija; Jankovic, Slobodan; Urosevic, Vlade; Ravlic, Miroslav; Vlajkovic, Marina


    Our team devised a real-time telemonitoring system (THYRPAN-TM) for measurement of the radiation exposure rate during the hospitalization of patients treated with high doses of radioiodine in the special premises with restricted access ("restricted area" [RA]). The THYRPAN-TM prototype was tested for stability, efficacy, and linearity in a 32-day measurement of a 110 MBq (131)I source. Furthermore, it was tested on 15 patients with differentiated thyroid carcinoma who stayed in the RA for 3 days, following their radioiodine treatment. Minor deviation from the theoretical values was detected when the (131)I source was measured by the THYRPAN-TM, but only at the beginning of the measurement (7.20%). THYRPAN-TM is a stable, user-friendly detection system for the measurement of the exposure rate following radioiodine administration. It enables the telemonitoring of patients, as well as real-time and online measurement of the whole-body burden of (131)I.

  14. Recombinant human TSH-aided radioiodine treatment of advanced differentiated thyroid carcinoma: a single-centre study of 54 patients

    Energy Technology Data Exchange (ETDEWEB)

    Jarzab, Barbara [Department of Nuclear Medicine and Endocrine Oncology, Centre of Oncology, Maria Sklodowska-Curie Memorial Institute, Gliwice Branch, Gliwice (Poland); Wybrzeze Armii Krajowej 15, 44-100, Gliwice (Poland); Handkiewicz-Junak, Daria; Roskosz, Jozef; Puch, Zbigniew; Wygoda, Zbigniew; Kukulska, Aleksandra; Jurecka-Lubieniecka, Beata; Hasse-Lazar, Kornelia; Turska, Maria [Department of Nuclear Medicine and Endocrine Oncology, Centre of Oncology, Maria Sklodowska-Curie Memorial Institute, Gliwice Branch, Gliwice (Poland); Zajusz, Aleksander [II Clinic of Radiotherapy, Centre of Oncology, Maria Sklodowska-Curie Memorial Institute, Gliwice Branch, Gliwice (Poland)


    In 54 consecutive patients who had retained bulky metastatic and/or locoregional lesions of DTC despite the exhaustion of other therapeutic options, we gave one to four courses of two consecutive daily intramuscular injections of rhTSH, 0.9 mg, followed by a therapeutic activity of {sup 131}I per os on day 3. Fifty patients had received prior radioiodine treatment aided by l-thyroxine (T{sub 4}) withdrawal. We included in the study 23 patients who had received a trial of isotretinoin therapy for re-differentiation of confirmed de-differentiated metastases. In a blinded, within-patient comparison of post-therapy whole-body scans after the first rhTSH-aided and latest withdrawal-aided treatments in patients with functional metastases at baseline, 18 of 27 (67%) scan pairs were concordant, four (15%) were discordant in favour of the rhTSH-aided scan and five (19%) were discordant in favour of the withdrawal-aided scan. In total, 37 (74%) of 50 paired scans were concordant, eight (16%) favoured rhTSH and five (10%) favoured withdrawal. All differences appeared to be attributable to clinical causes, not to any difference between endogenous and exogenous TSH stimulation. Reflecting the biochemical activity of rhTSH and the release of thyroglobulin (Tg) due to tumour destruction, median serum Tg concentration rose approximately fourfold between baseline and day 6 of the rhTSH-aided treatment course. rhTSH was well tolerated, with mostly minor, transient toxicity, except for neck oedema in three patients with neck infiltrates and pathological spine fracture in one patient with a large vertebral metastasis. At 6 months, complete response occurred in one (2%), partial response in 12 (26%) and disease stabilisation in 19 (40%) of 47 evaluable patients. The rate of complete + partial response was 41% and that of disease stabilisation, 30%, in the 27 evaluable patients with functional metastases at baseline; the corresponding rates were 10% and 55% in the 20 evaluable patients

  15. Lenvatinib and other tyrosine kinase inhibitors for the treatment of radioiodine refractory, advanced, and progressive thyroid cancer

    Directory of Open Access Journals (Sweden)

    Lorusso L


    Full Text Available Loredana Lorusso,1 Letizia Pieruzzi,1 Agnese Biagini,1 Elena Sabini,1 Laura Valerio,1 Carlotta Giani,1 Paolo Passannanti,1 Benedetta Pontillo-Contillo,2 Valentina Battaglia,2 Salvatore Mazzeo,2 Eleonora Molinaro,1 Rossella Elisei1 1Endocrine Unit, Department of Clinical and Experimental Medicine, 2Division of Diagnostic and Interventional Radiology, University of Pisa, Pisa, Italy Abstract: Lenvatinib is a small oral molecule able to inhibit three of the extracellular and intracellular molecules involved in the modulation of angiogenesis and lymphangiogenesis: vascular endothelial growth factor receptor 1–3, fibroblast growth factor receptor 1–4, and platelet-derived growth factor receptor alpha. Since it is also able to inhibit the REarranged during Transfection oncogene and the protooncogene c-KIT, this drug can also be used to control tumor cell proliferation. The maximum tolerated dose, as demonstrated in Phase I studies, is 25 mg daily. The drug is rapidly absorbed with maximum concentrations achieved within 3 and 5 hours after administration in fasting and nonfasting treated patients, respectively. The most common adverse events, reported in Phase I study and confirmed in the subsequent Phase II and III studies, are hypertension, proteinuria, and gastrointestinal symptoms such as nausea, diarrhea, and stomatitis. In Phase I studies, efficacy of lenvatinib in solid tumors was demonstrated, and these encouraging results have led to the development of a Phase II study using lenvatinib in advance radioiodine-refractory differentiated thyroid cancer (DTCs patients. Since an overall response rate of 50% was reported, this study also confirmed the efficacy of lenvatinib in DTCs patients with an acceptable toxicity profile. Recently, a Phase III study in patients with DTCs (SELECT study demonstrated the lenvatinib efficacy in prolonging progression-free survival with respect to the placebo (18.3 vs 3.6 months; P<0.001. Although there was no

  16. Preliminary evaluation of two radioiodinated maleimide derivatives targeting peripheral and membrane sulfhydryl groups for in vitro cell labeling

    Energy Technology Data Exchange (ETDEWEB)

    Amartey, John K., E-mail: [Cyclotron and Radiopharmaceuticals Department, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Parhar, Ranjit S. [Biological and Medical Research Department, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Shi, Yufei [Genetics Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Al-Mohanna, Futwan [Biological and Medical Research Department, P.O. Box 3354, Riyadh 11211 (Saudi Arabia)


    A factor impeding the advancement of cell mediated therapy is the inability to track these cells in vivo by noninvasive techniques. It has been shown that cells express high levels of sulfhydryl groups. We sought to explore these groups to covalently label cells with radiolabeled maleimide derivatives. Two maleimide derivatives; N-[2-(2,5-dioxoazolinyl)ethyl](5-iodo(3-pyridyl))carboxamide and N-[2-(2,5-dioxoazolinyl)ethyl](3-iodophenyl)carboxamide ([{sup 125}I]-4 and [{sup 125}I]-8) were synthesized and radioiodinated. These compounds were evaluated for in vitro binding to neutrophils, endothelial and mesenchymal stem cells, and biodistribution of the radiolabeled stem cells in nude mice. These radiotracers were obtained in moderate to high radiochemical yields. Binding to cells were moderate (20-60%/10{sup 6} cells) and the label was retained, although washout (an average of 18-55%) was observed depending on the cell type and the tracer used. The labeled cells initially localized in well perfused organs and at a later time showed a general distribution as expected. The novel tracers labeled several cell types and shown that the stability of the label and viability of the cells were maintained in vitro and in vivo for a reasonable period and warrant further in vivo investigation.

  17. Dyshormonal states of the reproductive system in women after thyroidectomy and radioiodine therapy for differentiated thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    A.M. Kvachenyuk


    Full Text Available Using ultrasound data and content of gonadotropin and sex hormones in the blood, the morphological and functional state of the mammary glands, the uterus and the ovaries were studied in women after thyroidectomy and radioiodine therapy, who were taken suppressive therapy with levothyroxine drugs that allows to estimate the hormonal supply of the menstrual cycle and the state of reproductive system. The signs of menstrual cycle disorders and luteal phase deficiency were revealed during the treatment, and dyshormonal hyperplasia of mammary glands was also diagnosed in 82.6 % of cases due to prolonged relative hyperestrogenism and hyperplastic diseases of the uterus and the ovaries, including genital endometriosis, endometrial hyperplasia, uterine myomas, were identified in 80.4 % of cases. A long-term monitoring (every 3 months of thyroid-stimulating hormone, thyroglobulin, thyroglobulin antibodies, follicle-stimulating hormone, luteinizing hormone, prolactin, progesterone, free testosterone, estradiol levels and also the correction of cycle supply using hormonal and non-hormonal methods are needed for this category of patients.

  18. Effect of glucose and insulin infusion on the myocardial extraction of a radioiodinated methyl-substituted fatty acid

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    Bianco, J.A.; Elmaleh, D.R.; Leppo, J.A.; King, M.A.; Moring, A.; Livni, E.; Espinoza, E.; Alpert, J.S.; Strauss, H.W.


    We investigated the one-way. An extraction of 14-iodophenyl-tetradecanoic acid (BMTDA) in the canine heart under fasting conditions and during infusion of glucose plus insulin in eight an esthetized greyhound dogs. Myocardial extraction measurements were made with dual tracer approach, using Tc-99m albumin as reference tracer. Prior to, and during, infusion of 10% glucose and 25 units of regular insulin, heart rate, blood pressure, plasma glucose, insulin and free fatty acid levels were measured. Myocardial blood flow was determined using Sn-113 and Ru-103 radioactive microspheres. The mean extraction fraction of BMTDA was 0.38+-SEM 0.06 at baseline and increased to 0.44+-0.06 during hyperglycemia plus insulin. Plasma glucose and insulin were higher during the infusion while plasma free fatty acids significantly declined. There were no changes in hemodynamics or myocardial blood flow during the infusion. We conclude that glucose and insulin infusion result in increased first-pass extraction fraction of radioiodinated BMTDA unaccompanied by changes in coronary flow or hemodynamics, implying an insulin-mediated augmented transport of BMTDA.

  19. Procedure guidelines for radioiodine therapy of differentiated thyroid cancer (version 2); Verfahrensanweisung zur Radioiodtherapie (RIT) beim differenzierten Schilddruesenkarzinom (Version 2)

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    Dietlein, M.; Dressler, J.; Farahati, J.; Gruenwald, F.; Leisner, E.; Moser, E.; Reiners, C.; Schicha, H.; Schober, O. [Deutsche Gesellschaft fuer Nuklearmedizin e.V., Hannover (Germany)


    The procedure guidelines for radioiodine therapy (RIT) of differentiated thyroid cancer (version 2) are the counterpart to the procedure guidelines for {sup 131}I whole-body scintigraphy (version 2) and specify the interdisciplinary guidelines for thyroid cancer of the Deutsche Krebsgesellschaft and the Deutsche Gesellschaft fuer Chirurgie concerning the nuclear medicine part. Compared with version 1 facultative options for RIT can be chosen in special cases: ablative RIT for papillary microcarcinoma {<=} 1 cm, ablative RIT for mixed forms of anaplastic and differentiated thyroid cancer, and RIT in patients with a measurable or increasing thyroglobulin concentration but without detectable metastases by imaging. The description of the pretherapeutic dosimetry now includes the isotopes {sup 123}I and {sup 124}I as well as a broader range of the activity of {sup 131}I. Activities of 2-5 GBq {sup 131}I are recommended for the first ablative RIT. If high accumulative activities of {sup 131}I are expected, men who have not yet finished their family planning should be advised to the option of sperm cryoconservation. An interdisciplinary consensus is necessary whether the new TNM-classification (UICC, 6{sup th} edition, 2002) will lead to modified recommendations for surgical or nuclear medicine therapy, especially for the surgical completeness and for the ablative RIT of pT1 papillary cancer. (orig.)

  20. High-performance liquid chromatography of 125I-labeled mouse epidermal growth factor radioiodinated by six different methods. (United States)

    Kienhuis, C B; Heuvel, J J; Ross, H A; Foekens, J A; Benraad, T J


    Six different procedures for radioiodination of mouse epidermal growth factor (EGF) all resulted in a heterogeneous 125I-labeled EGF preparation, as analyzed by reversed-phase HPLC. EGF preparations that had been iodinated with Chloramine T, lodogen, or lodo-beads were found mainly to consist of oxidized 125I-labeled EGF moieties. In contrast, the heterogeneous 125I-labeled EGF preparations obtained by using iodine monochloride, Protag-125, or lactoperoxidase-glucose oxidase-coupled beads (Enzymobeads) contained insignificant amounts of oxidized EGF entities. Ligand equivalence analysis (LEA) of distinct HPLC column fractions, obtained after preparative separation of Chloramine T-125I-labeled EGF, showed that the receptor-binding affinity of the tracer in all subfractions was less than the affinity of unlabeled EGF. This implies that HPLC purification of these 125I-labeled EGF preparations does not yield 125I-labeled EGF preparations with ligand equivalence. However, all but one HPLC column fraction of Enzymobeads-125I-labeled EGF showed ligand equivalence. Despite the small amount of the nonequivalent component in the Enzymobeads-labeled tracer, the nonchromatographed 125I-labeled EGF preparation showed ligand equivalence. No significant differences were observed in the maximal binding capacity of the different 125I-labeled EGF preparations.

  1. Procedure guidelines for radioiodine therapy of differentiated thyroid cancer (version 3); Verfahrensanweisung zur Radioiodtherapie (RIT) beim differenzierten Schilddruesenkarzinom (Version 3)

    Energy Technology Data Exchange (ETDEWEB)

    Dietlein, M.; Schicha, H. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Koeln Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Dressler, J. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Nuklearmedizinsiche Klinik der Henriettenstiftung, Hannover (Germany); Eschner, W. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Deutsche Gesellschaft fuer Medizinische Physik (DGMP) (Germany); Koeln Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Gruenwald, F. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Frankfurt Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Lassmann, M. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Deutsche Gesellschaft fuer Medizinische Physik (DGMP) (Germany); Wuerzburg Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Leisner, B. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Allgemeines Krankenhaus St. Georg, Hamburg (Germany); Luster, M.; Reiners, C. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Wuerzburg Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Moser, E. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Radiologische Universitaetsklinik Freiburg (Germany); Schober, O. [Deutsche Gesellschaft fuer Nuklearmedizin (DGN) (Germany); Muenster Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin


    The procedure guideline for radioiodine therapy (RIT) of differentiated thyroid cancer (version 3) is the counterpart to the procedure guideline for {sup 131}I whole-body scintigraphy (version 3) and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. Recommendation for ablative {sup 131}I therapy is given for all differentiated thyroid carcinoma (DTC) >1 cm. Regarding DTC {<=}1 cm {sup 131}I ablation may be helpful in an individual constellation. Preparation for {sup 131}I ablation requires low iodine diet for two weeks and TSH stimulation by withdrawal of thyroid hormone medication or by use of recombinant human TSH (rhTSH). The advantages of rhTSH (no symptoms of hypothyroidism, lowerblood activity) and the advantages of endogenous TSH stimulation (necessary for {sup 131}I-therapy in patients with metastases, higher sensitivity of {sup 131}I whole-body scan) are discussed. In most centers standard activities are used for {sup 131}I ablation. If pretherapeutic dosimetry is planned, the diagnostic administration of {sup 131}I should not exceed 1-10MBq, alternative tracers are {sup 123}I or {sup 124}I. The recommendations for contraception and family planning are harmonized with the recommendation of ATA and ETA. Regarding the best possible protection of salivary glands the evidence is insufficient to recommend a specific setting. To minimize the risk of dental caries due to xerostomia patients should use preventive strategies for dental hygiene. (orig.)

  2. Distribution and transfer of radiocesium and radioiodine in the environment following the Fukushima nuclear accident - Distribution and transfer of radiocesium and radioiodine in the environment of Fukushima Prefecture following the nuclear accident

    Energy Technology Data Exchange (ETDEWEB)

    Muramatsu, Yasuyuki; Ohno, Takeshi; Sugiyama, Midori [Gakushuin University, Toshima-ku, Tokyo, 171-8588 (Japan); Sato, Mamoru [Fukushima Agricultural Technology Centre, Koriyama, Fukushima 963-0531 (Japan); Matsuzaki, Hiroyuki [The University of Tokyo, Bunkyo-ku, Tokyo 113-8656 (Japan)


    Large quantities of radioiodine and radiocesium were released from the accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP) in March 2011. We have carried out intensive studies on the distribution and behaviour of these nuclides in the environment following the accident. Two topics obtained from our studies are presented. (1) Retrospective estimation of I-131 deposition through the analysis of I-129 in soil: It is necessary to obtain deposition data of radioiodine in Fukushima Prefecture for the assessment of thyroid doses due to the accident. However, short half-life of I-131 (8 days) made it impossible to obtain adequate sample coverage that would permit direct determination of the regional deposition patterns of I-131 within the prefecture and surrounding areas. On the other hand, I-129 released simultaneously during the accident still remains in soil, due to its long half-life of 1.57x10{sup 7} years. In order to reconstruct the I-131 deposition, we have determined I-129 concentrations by accelerator mass spectrometry (AMS). A good correlation was found between the measured concentrations of I-131 and I-129 in soils collected in the vicinity of FDNPP. We have analyzed I-129 in more than 500 soil samples collected systematically from Fukushima Prefecture. Using the obtained results, the I-131 deposition was calculated in different areas and the deposition map for I-131 was constructed. We also studied the vertical distribution of I-129 in soil. (2) Peculiar accumulation of radiocesium to some plants and mushrooms The radioactivity levels in agricultural crops decreased markedly in some months following the accident and their concentrations became lower than the Japanese guideline for foodstuffs (500 Bq/kg in 2011, and 100 Bq/kg after 2012). However, some agricultural products such as tea leaves and citrus fruits showed relatively higher values. Our analytical results obtained for the distribution of radiocesium in tea trees show that the root uptake

  3. Cost-effectiveness of using recombinant human thyroid-stimulating hormone before radioiodine ablation for thyroid cancer treatment in Spanish hospitals. (United States)

    Vallejo, J A; Muros, M A

    In thyroid cancer treatment, the thyroid-stimulating hormone (TSH) must be elevated before radioiodine ablation, either by exogenous (with recombinant human thyrotropin [rhTSH]) or endogenous stimulation by thyroid hormone withdrawal (THW). The use of rhTSH avoids hypothyroidism and favours the subsequent elimination of radioiodine, but involves the cost of the product. For this reason, a cost-effectiveness analysis was performed, taking into account all costs involved and the benefits associated with the use of this therapy. Using a Markov modelling with two analysis arms (rhTSH and THW), stratified into high (100mCi/3700 MBq) and low (30mCi/1110 MBq) radioiodine doses, and using 17 weekly cycles, the incremental cost per quality-adjusted life-year (QALY) related to the use of rhTSH was determined. The clinical inputs included in the model were based on published studies and in a treatment survey conducted in Spain. Radioablation preparation with rhTSH is superior to THW, showing additional benefits (0.048 AVAC), as well as cost savings (-€614.16), with an incremental cost-effectiveness rate (ICER) of -€12,795/QALY. The univariate and multivariate sensitivity analyses showed the result to be robust. The use of rhTSH previous to radioablation in Spain has cost savings, as well as a series of health benefits for the patient, making it highly cost-effective. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  4. Iodine distribution in natural waters of different chemical composition in relation to water-bearing soils and rocks and water fractions in areas subjected to radioiodine contamination (United States)

    Kolmykova, Liudmila; Korobova, Elena


    Iodine is an essential microelement required for normal functioning of thyroid gland. Natural deficiency of stable iodine is compensated by its active intake by thyroid and provokes its higher irradiation in case of radiation accidents and contamination of the environment by radioiodine isotopes. The bioavailability of both stable and radioactive iodine and the specificity of its uptake by living organisms largely depends on geochemical parameters of the environment related to natural conditions of water migration. The goal of the study was to investigate spatial distribution of iodine in natural water of different chemical composition in relation to typical water-bearing soils and rocks and water fractions in Bryansk areas subjected to radioiodine contamination after the Chernobyl accident and to evaluate contribution of this factor to the occurrence of endemic thyroid diseases among local population inhabiting geochemically different areas of fluvioglacial and loess-like sedimentary rocks. The highest content of iodine (Me=13.3 µg/l) was observed in surface water of landscapes with H-Ca, Ca and H-Ca-Fe classes of water migration. The lowest microelement level (Me=5.25 µg/l) was noted in groundwater of landscapes with H, H-Fe classes of water migration in areas of Paleogene water bearing rocks. Regardless of the type of source and class of water migration up to 90% of the total content of iodide is present in the fraction membrane filtration). Up to 50% of iodine pass to solution containing particles water in areas of loess-like sedimentary rocks hosts the highest levels of iodine where its associated with calcium mineral aquatic complexes and the suspended particles. The obtained data is believed to be useful in explanation of mobility and intake of iodine and its radioactive analogues by rural population living in different geochemical conditions and using local drinking waters. The data should be accounted of in planning prophylactics of endemic diseases and

  5. Use of recombinant human thyrotropin (rh TSH) as a method of preparation for radioiodine therapy in thyroid disorders; Utilisation de la thyreostimuline humaine recombinante dans la preparation au traitement par iode-131 des pathologies thyroidiennes

    Energy Technology Data Exchange (ETDEWEB)

    Taieb, D.; Guillet, B.A.; Tessonnier, L.; Mundler, O. [Centre Hospitalo-Universitaire de la Timone, Service Central de Biophysique et de Medecine Nucleaire, 13 - Marseille (France)


    The introduction of recombinant human TSH (rh TSH) as a method of preparation for radioiodine therapy of follicular-derived thyroid tumors (benign and malignant) is a significant medical advance. Rh TSH has been approved for use in remnants ablation after total thyroidectomy for carcinoma. There are other potential uses for rh TSH that have not yet been licensed. The use of rh TSH allows to reduce administrated doses in goiters through an increase of iodine uptake and a more homogeneous distribution of radioiodine in the gland. Rh TSH also improves thyroid cancer patients quality of life by avoiding hypothyroidism. (authors)

  6. Radioiodine therapy in Graves' disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Reinhardt, Michael J.; Joe, Alexius Y.; Mallek, Dirk von; Ezziddin, Samer; Palmedo, Holger [Department of Nuclear Medicine, University Hospital of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Brink, Ingo [Department of Nuclear Medicine, University Hospital of Freiburg (Germany); Krause, Thomas M. [Department of Nuclear Medicine, Inselspital Bern (Switzerland)


    This study was performed with three aims. The first was to analyse the effectiveness of radioiodine therapy in Graves' disease patients with and without goitres under conditions of mild iodine deficiency using several tissue-absorbed doses. The second aim was to detect further parameters which might be predictive for treatment outcome. Finally, we wished to determine the deviation of the therapeutically achieved dose from that intended. Activities of 185-2,220 MBq radioiodine were calculated by means of Marinelli's formula to deliver doses of 150, 200 or 300 Gy to the thyroids of 224 patients with Graves' disease and goitres up to 130 ml in volume. Control of hyperthyroidism, change in thyroid volume and thyrotropin-receptor antibodies were evaluated 15{+-}9 months after treatment for each dose. The results were further evaluated with respect to pre-treatment parameters which might be predictive for therapy outcome. Thyroidal radioiodine uptake was measured every day during therapy to determine the therapeutically achieved target dose and its coefficient of variation. There was a significant dose dependency in therapeutic outcome: frequency of hypothyroidism increased from 27.4% after 150 Gy to 67.7% after 300 Gy, while the frequency of persistent hyperthyroidism decreased from 27.4% after 150 Gy to 8.1% after 300 Gy. Patients who became hypothyroid had a maximum thyroid volume of 42 ml and received a target dose of 256{+-}80 Gy. The coefficient of variation for the achieved target dose ranged between 27.7% for 150 Gy and 17.8% for 300 Gy. When analysing further factors which might influence therapeutic outcome, only pre-treatment thyroid volume showed a significant relationship to the result of treatment. It is concluded that a target dose of 250 Gy is essential to achieve hypothyroidism within 1 year after radioiodine therapy in Graves' disease patients with goitres up to 40 ml in volume. Patients with larger goitres might need higher doses

  7. Clinical Usefulness of F-18 FDG PET/CT in papillary thyroid cancer with negative radioiodine scan and elevated thyroglobulin level or positive anti-thyroglobulin antibody

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Su Jung; Jung, Kyung Pyo; Lee, Sun Seong; Park, Yun Soo; Lee, Seok Mo [Dept. of Nuclear Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of); Bae, Sang Kyun [Dept. of Nuclear Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)


    Elevated thyroglobulin (Tg) levels, along with a negative radioiodine scan, present a clinical problem for the diagnosis of recurrence in papillary thyroid cancer (PTC) patients. The purpose of this study was to assess (1) the usefulness of 18F-fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) for PTC patients with negative diagnostic radioiodine scan and elevated serum Tg level or positive anti-thyroglobulin antibody (TgAb), and (2) the effect of endogenous thyroid stimulating hormone (TSH) stimulation (ETS) on detecting recurrence in these circumstances. Eighty-four patients with negative diagnostic radioiodine scan and elevated serum Tg or positive TgAb under ETS were included. Correlation with clinicopathological features and recurrence, detectability of FDG PET/CT and cut-off value of serum Tg for recurrence in PTC patients with these circumstance were assessed. In addition, detectability of F-18 FDG PET/CT under ETS and suppression were compared. In Cox regression analysis, only serum Tg level was significantly associated with recurrence (P<0.001, HR  = 1.13; 95 % CI, 1.061–1.208). The cut-off level of Tg was 21.5 ng/mL (AUC, 0.919; P < 0.001) for discriminating the recurrence in the patients with positive PET/CT finding. The sensitivity, specificity, PPV, NPV, and accuracy of F-18 FDG PET/CT for detecting recurrence were 64 %, 94 %, 86 %, 81 %, and 83 %. In the analysis of F-18 FDG PET/CT under ETS, the sensitivity, specificity, PPV, NPV and accuracy was 64 %, 94 %, 88 %, 81 % and 83 %. Those under TSH suppression were 67 %, 92 %, 80 %, 85 % and 83 %. F-18 FDG PET/CT, although less sensitive, showed high specificity, PPV, NPV, and accuracy and therefore can be useful for the patients with negative diagnostic radioiodine scan and elevated serum Tg or positive TgAb. In addition, FDG PET/CT under ETS does not seem to have an additive role in detecting recurrence in these patients.

  8. Is soil natural organic matter a sink or source for mobile radioiodine ( 129 I) at the Savannah River Site? (United States)

    Xu, Chen; Zhang, Saijin; Ho, Yi-Fang; Miller, Eric J.; Roberts, Kimberly A.; Li, Hsiu-Ping; Schwehr, Kathleen A.; Otosaka, Shigeyoshi; Kaplan, Daniel I.; Brinkmeyer, Robin; Yeager, Chris M.; Santschi, Peter H.


    . These differences in iodination are due to different SOM molecular sizes, compositions, and availability of preferred iodination sites. 129I in the soil downstream from the contaminated site and near a wetland abruptly dropped below our detection limit (0.5 pCi- 129I/g-soil), which suggests that the high SOM in the plume soil around the 129I-contaminated F-Area might be a natural barrier to scavenge radioiodine released from the nuclear waste repository by forming organo-iodine compounds. Soil resuspension experiments showed that mobile 129I was mostly associated with a low average molecular weight amphiphilic organic carrier (13.5-15 kDa). SOM clearly behaves as a sink for iodine at the Savannah River Site F-Area. However, this work demonstrates that a small fraction of the SOM can also behave as a source, namely that a small fraction that may be readily dispersible under some environmental conditions and presumably release iodine in the organic-colloidal form. This radioiodinated organo-colloid likely can get into the groundwater through infiltration or surface runoff where it might migrate further into the wetlands. Results from this study provide the geochemical basis for future 129I migration controls, remediation, and/or land-groundwater management strategies.

  9. Effect of the Fukushima nuclear power plant accident on radioiodine (¹³¹ I) content in human breast milk. (United States)

    Unno, Nobuya; Minakami, Hisanori; Kubo, Takahiko; Fujimori, Keiya; Ishiwata, Isamu; Terada, Hiroshi; Saito, Shigeru; Yamaguchi, Ichiro; Kunugita, Naoki; Nakai, Akihito; Yoshimura, Yasunori


    Environmental pollution with radioiodine (iodine-131, (131) I) occurred after an accident at the Fukushima nuclear power plant (FNP) on March 11, 2011, in Japan. Whether environmental pollution with (131) I can contaminate human breast milk has not been documented. The (131) I content was determined in 126 breast milk samples from 119 volunteer lactating women residing within 250 km of the FNP, between April 24 and May 31, 2011. The degree of environmental pollution was determined based on the data released by the Japanese government. An (131) I content of 210 Bq/kg in the tap water in Tokyo, which is located 230 km south of the FNP, on March 22 and of 3500 Bq/kg in spinach sampled in a city located 140 km southwest of the FNP on March 19 decreased over time to <21 Bq/kg on March 27 and 12 Bq/kg on April 26, respectively. Seven of the 23 women who were tested in April secreted a detectable level of (131) I in their breast milk. The concentrations of (131) I in the breast milk of the seven women were 2.3 Bq/kg (on April 24), and 2.2, 2.3, 2.3, 3.0, 3.5 and 8.0 (on April 25); the concentrations of (131) I in the tap water available for these seven women at the same time were estimated to be <1.3 Bq/kg. None of the remaining 96 women tested in May exhibited a detectable concentration of (131) I in their breast milk samples. The contamination of breast milk with (131) I can occur even when only mild environmental (131) I pollution is present. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  10. Combined use of radioiodine therapy and radiofrequency ablation in treating postsurgical thyroid remnant of differentiated thyroid carcinoma. (United States)

    Long, Bin; Li, Linfa; Yao, Lifang; Chen, Shoucong; Yi, Heqing; Ye, Xuemei; Xu, Dong; Wu, Peng


    To determine whether postoperative radioiodine (RAI) combined with radiofrequency ablation (RFA) is an effective, safe, and feasible method for elimination of excessive postsurgical thyroid remnant for differentiated thyroid carcinoma (DTC). We took a prospective study and treated 12 DTC patients (4 males, 8 females, age 20-78 years) who underwent thyroidectomy for RFA followed by 131 I ablation. The pretreatment requires iodine-free diet and thyroid hormone withdrawal for 3-4 week. All the patients showed the level of serum thyroid-stimulating hormone (TSH) thyroid remnant in 99m Technetium (99m Tc) imaging. Serum TSH level was determined 1 day before RFA and on days 1, 7, 14 after RFA, and 99m Tc imaging was performed on day 14 after RFA. Subsequently, the patients were given an oral dosage of 3700 MBq 131 I for remnant ablation, and posttreatment whole body scan was performed on day 5 after ablation. Efficacy evaluation was done 4-6 months after treatment. The changes of variants before and after RFA were analyzed using Wilcoxon signed rank sum test. Serum TSH was thyroid remnant ablation was 91.7% (11/12), which was assessed 4-6 months after treatment. All patients reported neck discomfort and some are self-limiting, with no hoarseness, choking, or radiation thyroiditis symptoms. Five patients had puncture area pain, among which one patient had neck edema, which was relieved after prednisone treatment. Combined use of RAI therapy and radiofrequency ablation in treating excessive postsurgical thyroid remnant of DTC can be an effective approach and avoids re-operation. Long-term efficacy monitoring would further determine its feasibility.

  11. Pituitary binding and internalization of radioiodinated gonadotropin-releasing hormone agonist and antagonist ligands in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wynn, P.C.; Suarez-Quian, C.A.; Childs, G.V.; Catt, K.J.


    In rat pituitary gonadotrophs, the rates of binding and endocytosis of two GnRH superagonist analogs, (D-Ala6,Pro9-NEt)GnRH and (D-Lys6,Pro9-NEt)GnRH, were compared with those of the potent antagonist analog (N-acetyl-D-pCl-Phe1,2,D-Trp3,D-Lys6,D-Ala10)GnRH by quantitative electron microscopic autoradiography. In dispersed pituitary cells, the two agonist analogs showed similar binding kinetics and comparable degrees of sequestration, as measured by their resistance to dissociation by low pH buffer. However, quantification of silver grain localization suggested that cellular internalization of the (D-Ala6)GnRH agonist increased more rapidly than that of the (D-Lys6)GnRH analog. These discrepancies, and the finding that a larger amount of the specifically bound /sup 125/I-(D-Ala6)GnRH agonist was removed during glutaraldehyde fixation, indicated that the proportional internalization of this analog was over estimated by quantitative autoradiography owing to loss of cell surface-bound radioligand. We, therefore, employed radioiodinated D-Lys6-substituted analogs to analyze the receptor binding and cellular uptake of GnRH agonist and antagonist derivatives in vivo. After iv injection, a high proportion of the /sup 125/I-(D-Lys6)GnRH agonist was translocated into pituitary gonadotrophs within 60 min, whereas the D-Lys6 antagonist was predominantly associated with the plasma membrane during that time. Four hours after injection of the antagonist, an appreciable proportion of silver grains was associated with intracellular organelles, and this trend increased progressively at later time points. The relatively prolonged cellular processing of the GnRH antagonist is consistent with in vivo binding kinetics, and its slower internalization may reflect the basal rate of GnRH receptor turnover in the cell membrane.

  12. Minimally invasive local ablative therapies in combination with radioiodine therapy in benign thyroid disease: preparation, feasibility and efficiency - preliminary results. (United States)

    Mader, Alexander; Mader, Oscar Maximilian; Gröner, Daniel; Korkusuz, Yücel; Ahmad, Shadi; Grünwald, Frank; Kranert, W Tilman; Happel, Christian


    Initial studies of combinations of radioiodine therapy (RIT) and local ablative procedures for the treatment of thyroid nodules have shown promising results. The goal of this study was to evaluate the effectiveness of RIT combined with radiofrequency ablation (RFA) in patients with goitres and to determine which ablative procedure is the most suitable for a combined therapy. Thirty patients with goitres were divided into two subgroups. A test group of 15 patients received combined therapy (RIT + RFA) and a control group of 15 patients received RIT mono therapy. All patients underwent assessments including ultrasound, laboratory evaluation (T3, T4, TSH, TG, TPOAb, TgAbTRAb) and scintigraphic imaging with Tc-99m-Pertechnetate. The 3-month volume reduction was used to evaluate therapy effectiveness. Combined therapy (subgroup 1) resulted in a significant (p  0.05) than the control group (20.2 ± 32.2 ml/29.6 ± 42.1%). All patients became euthyroid after treatment. No major discomfort or complications occurred. A review of the literature investigating combinations of other local ablative procedures with RIT was performed to determine the most promising combination. The present study confirms the positive experiences with the combined therapy of RIT and local ablative procedures shown in the current literature and approves this approach for the treatment of goitres with RFA + RIT. These findings, when confirmed by further studies, should expand the indication of combined therapy as a minimally invasive alternative to surgery.

  13. Incidental findings of intense radioiodine uptake in struma ovarii and bilateral nonlactating breasts simultaneously on postablation {sup 131}I SPECT/CT for papillary thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Hye Kyung; Kim, Mi Ra [Haeundae Paik HospitalUniversity of Inje, College of Medicine, Busan (Korea, Republic of)


    A 52-year-old woman diagnosed with papillary thyroid carcinoma was referred for {sup 131}I therapy following total thyroidectomy. She was given 4,810 MBq (130 mCi) of {sup 131}I following 4 weeks of thyroid hormone withdrawal. A post therapy scan showed intense, focal activity in the pelvis and intense, diffuse activity on both sides of the chest, which was localized to the right ovary and both breasts on SPECT/CT examination. She had bilateral nipple pain and a history of antidopaminergic drugs as combination medication for her rheumatoid arthritis and prokinetics during radioiodine therapy. On a {sup 123}I whole-body scan 9 months later after stopping the drugs, bilateral breast uptake was not visible; however, right ovarian focal uptake was still visualized. Bilateral salpingo-oophorectomy was performed, and revealed struma ovarii with substantial internal necrosis due to radioiodine therapy. This case is interesting as two rare entities, {sup 131}I therapy-related struma ovarii and drug-related breast uptake, were simultaneously visualized.


    Zhang, Qing; Guan, Yanxing; Xiang, Tianxin; Liu, Shaozheng; Chen, Qingjie; Zhang, Qing


    The treatment of hyperthyroidism associated with severe liver dysfunction (LD) is a clinical challenge, and there has been no unified examination of this problem. The objective of this study was to assess the efficacy and safety of radioiodine (131I) in combination with a molecular adsorbent recirculating system (MARS) for the treatment of hyperthyroidism complicated by severe liver LD. A total of 116 hyperthyroidism patients with concomitant LD who received MARS treatment were studied retrospectively. The patients were grouped according to whether or not they also received 131I treatment: Group 1 (59 patients) received 131I following MARS treatment, while Group 2 (57 cases) received only MARS. Clinical outcomes, including thyroid hormone levels, liver function parameters, and therapeutic efficacy were calculated. The overall response rate was significantly greater in Group 1 than in Group 2 (Phyperthyroidism complicated by severe LD was effective and safe. The use of this system could rapidly improve liver function and metabolism, allowing 131I therapy to be applied as early as possible with a shortened recovery time of liver function. ALSS = artificial liver support system ALT = alanine transaminase AST = aspartate transaminase ATD = antithyroid drugs DBil = direct bilirubin FT3 = free tri-iodothyronine FT4 = free thyroxine 131I = radioiodine INR = international normalized ratio LD = liver dysfunction MARS = molecular adsorbent recirculating system MELD = model for end-stage liver disease PT = prothrombin time TBil = total bilirubin TSH = thyroid-stimulating hormone.

  15. Radioiodine therapy in elderly patients with subclinical hyperthyroidism due to non-voluminous nodular goiter and its effect on bone metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Rosario, Pedro Weslley [Santa Casa de Belo Horizonte, MG (Brazil). Endocrinology Service


    Objective: To evaluate {sup 131}I therapy in elderly patients with subclinical hyperthyroidism (SCH) due to nodular disease and who did not receive antithyroid drugs (ATDs), and the effect of the treatment on bone metabolism. Subjects and methods: Thirty-six patients with TSH {<=} 0.1mIU/L and non-voluminous goiter (< 60 cm{sup 3} were studied. Bone mineral density (BMD) was assessed in 17 women with osteopenia. Results: Mean 24-h {sup 131}I uptake was 17.5%. Symptoms of thyrotoxicosis were reported by two (5.5%) patients in the first week after therapy. One year after radioiodine treatment, SCH was resolved in 30 (83.3%) patients, and hypothyroidism was detected in one (2.7%). In the patients in whom TSH returned to normal, femoral and lumbar spine BMD increased by 1.9% and 1.6%, respectively, in average. Conclusions: In elderly patients with SCH and non-voluminous goiter, radioiodine not preceded by ATDs is a safe and effective therapeutic alternative. Resolution of SCH has beneficial effects on BMD in postmenopausal women with osteopenia. (author)

  16. Fluorous Analogue of Chloramine-T: Preparation, X-ray Structure Determination, and Use as an Oxidant for Radioiodination and s-Tetrazine Synthesis. (United States)

    Dzandzi, James P K; Beckford Vera, Denis R; Genady, Afaf R; Albu, Silvia A; Eltringham-Smith, Louise J; Capretta, Alfredo; Sheffield, William P; Valliant, John F


    A fluorous oxidant that can be used to introduce radioiodine into small molecules and proteins and generate iodinated tetrazines for bioorthogonal chemistry has been developed. The oxidant was prepared in 87% overall yield by combining a fluorous amine with tosyl chloride, followed by chlorination using aqueous sodium hypochlorite. A crystal structure of the oxidant, which is a fluorous analogue of chloramine-T, was obtained. The compound was shown to be stable for 7 days in EtOH and for longer than three months as a solid. The oxidant was effective at promoting the labeling of arylstannanes using [(125)I]NaI, where products were isolated in high specific activity in yields ranging from 46% to 86%. Similarly, iodinated biologically active proteins (e.g., thrombin) were successfully produced, as well as a radioiodinated tetrazine, through a concomitant oxidation-halodemetalation reaction. Because of its fluorous nature, unreacted oxidant and associated reaction byproducts can be removed quantitatively from reaction mixtures by passing solutions through fluorous solid phase extraction cartridges. This feature enables rapid and facile purification, which is critical when working with radionuclides and is similarly beneficial for general synthetic applications.

  17. Abnormal radioiodine uptake on post-therapy whole body scan and sodium/iodine symporter expression in a dermoid cyst of the ovary: report of a case and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Campenni, Alfredo; Baldari, Sergio, E-mail: acampenni@unime.ittalia [Dipartimento di Scienze Biomediche e delle Immagini Morfologiche e Funzionali, Unità di Medicina Nucleare, Università degli Studi di Messina, Messina (Italy); Giovinazzo, Salvatore; Ruggeri, Rosaria M. [Dipartimento di Medicina Clinica e Sperimentale, Unità di Endocrinologia, Università degli Studi di Messina (Italy); Tuccari, Giovanni [Dipartimento di Patologia Umana, Università degli Studi di Messina (Italy); Fogliani, Simone [Unità di Scienze Radiologiche, Ospedale di Milazzo, Messina (Italy)


    In patients affected by differentiated thyroid cancer, the whole-body scan (WBS) with 131-radioiodine, especially when performed after a therapeutic activity of {sup 131}I, represents a sensitive procedure for detecting thyroid remnant and/or metastatic disease. Nevertheless, a wide spectrum of potentially pitfalls has been reported. Herein we describe a 63-year-old woman affected by follicular thyroid cancer, who was accidentally found to have an abdominal mass at post-dose WBS (pWBS). pWBS showed abnormal radioiodine uptake in the upper mediastinum, consistent with lymph-node metastases, and a slight radioiodine uptake in an abdominal focal area. Computed tomography revealed an inhomogeneous mass in the pelvis, previously unrecognized. The lesion, surgically removed, was found to be a typical dermoid cyst of the ovary, without any evidence of thyroid tissue. By immunohistochemistry, a moderate expression of the sodium-iodine symporter (NIS) was demonstrated in the epithelial cells, suggesting a NIS-dependent uptake of radioiodine by the cyst. (author)

  18. Radioiodine plus recombinant human thyrotropin do not cause acute airway compression and are effective in reducing multinodular goiter

    Energy Technology Data Exchange (ETDEWEB)

    Albino, C.C., E-mail: [Instituto de Diabetes e Endocrinologia de Maringa, PR (Brazil); Graf, H.; Paz-Filho, G. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Hospital das Clinicas. Servico de Endocrinologia e Metabologia; Diehl, L.A. [Universidade Estadual de Londrina (UEL), PR (Brazil); Olandoski, M.; Sabbag, A. [Pontificia Univ. Catolica do Parana (PUCPR), Curitiba, PR (Brazil). Nucleo de Bioestatistica; Buchpiguel, C. [Universidade de Sao Paulo (USP), SP (Brazil). Dept. de Radiologia


    Recombinant human thyrotropin (rhTSH) reduces the activity of radioiodine required to treat multinodular goiter (MNG), but acute airway compression can be a life-threatening complication. In this prospective, randomized, double-blind, placebo-controlled study, we assessed the efficacy and safety (including airway compression) of different doses of rhTSH associated with a fixed activity of {sup 131}I for treating MNG. Euthyroid patients with MNG (69.3 +- 62.0 mL, 20 females, 2 males, 64 +- 7 years) received 0.1 mg (group I, N = 8) or 0.01 mg (group II, N = 6) rhTSH or placebo (group III, N = 8), 24 h before 1.11 GBq {sup 131}I. Radioactive iodine uptake was determined at baseline and 24 h after rhTSH and thyroid volume (TV, baseline and 6 and 12 months after treatment) and tracheal cross-sectional area (TCA, baseline and 2, 7, 180, and 360 days after rhTSH) were determined by magnetic resonance; antithyroid antibodies and thyroid hormones were determined at frequent intervals. After 6 months, TV decreased significantly in groups I (28.5 +- 17.6%) and II (21.6 +- 17.8%), but not in group III (2.7 +- 15.3%). After 12 months, TV decreased significantly in groups I (36.7 +- 18.1%) and II (37.4 +- 27.1%), but not in group III (19.0 +- 24.3%). No significant changes in TCA were observed. T3 and free T4 increased transiently during the first month. After 12 months, 7 patients were hypothyroid (N 3 in group I and N = 2 in groups II and III). rhTSH plus a 1.11-GBq fixed {sup 131}I activity did not cause acute or chronic changes in TCA. After 6 and 12 months, TV reduction was more pronounced among patients treated with rhTSH plus {sup 131}I (author)

  19. Comparative Analysis of T Cell Imaging with Human Nuclear Reporter Genes. (United States)

    Moroz, Maxim A; Zhang, Hanwen; Lee, Jason; Moroz, Ekaterina; Zurita, Juan; Shenker, Larissa; Serganova, Inna; Blasberg, Ronald; Ponomarev, Vladimir


    Monitoring genetically altered T cells is an important component of adoptive T cell therapy in patients, and the ability to visualize their trafficking/targeting, proliferation/expansion, and retention/death using highly sensitive reporter systems that do not induce an immunologic response would provide useful information. Therefore, we focused on human reporter gene systems that have the potential for translation to clinical studies. The objective of the in vivo imaging studies was to determine the minimum number of T cells that could be visualized with the different nuclear reporter systems. We determined the imaging sensitivity (lower limit of T cell detection) of each reporter using appropriate radiolabeled probes for PET or SPECT imaging. Human T cells were transduced with retroviral vectors encoding for the human norepinephrine transporter (hNET), human sodium-iodide symporter (hNIS), a human deoxycytidine kinase double mutant (hdCKDM), and herpes simplex virus type 1 thymidine kinase (hsvTK) reporter genes. After viability and growth were assessed, 10(5) to 3 × 10(6) reporter T cells were injected subcutaneously on the shoulder area. The corresponding radiolabeled probe was injected intravenously 30 min later, followed by sequential PET or SPECT imaging. Radioactivity at the T cell injection sites and in the thigh (background) was measured. The viability and growth of experimental cells were unaffected by transduction. The hNET/meta-(18)F-fluorobenzylguanidine ((18)F-MFBG) reporter system could detect less than 1 × 10(5) T cells because of its high uptake in the transduced T cells and low background activity. The hNIS/(124)I-iodide reporter system could detect approximately 1 × 10(6) T cells; (124)I-iodide uptake at the T cell injection site was time-dependent and associated with high background. The hdCKDM/2'-(18)F-fluoro-5-ethyl-1-β-d-arabinofuranosyluracil ((18)F-FEAU) and hsvTK/(18)F-FEAU reporter systems detected approximately 3 × 10(5) T cells

  20. Evaluation of radioiodinated (2S,{alpha}S)-2-({alpha}-(2-iodophenoxy)benzyl)morpholine as a radioligand for imaging of norepinephrine transporter in the heart

    Energy Technology Data Exchange (ETDEWEB)

    Kiyono, Yasushi [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan)], E-mail:; Sugita, Taku [Department of Pathofunctional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Ueda, Masashi [Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Kawashima, Hidekazu [Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Kanegawa, Naoki; Kuge, Yuji [Department of Pathofunctional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Saji, Hideo [Department of Pathofunctional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)


    Introduction: The norepinephrine transporter (NET) is located presynaptically on noradrenergic nerve terminals and plays a critical role in the regulation of the synaptic norepinephrine (NE) concentration via the reuptake of NE. Changes in NET have been recently reported in several cardiac failures. Therefore, a NET-specific radioligand is useful for in vivo assessment of changes in NET density in various cardiac disorders. Recently, we developed a radioiodinated reboxetine analogue, (2S,{alpha}S)-2-({alpha}-(2-iodophenoxy)benzyl)morpholine ((S,S)-IPBM), for NET imaging. In the current study, we assessed the applicability of radioiodinated (S,S)-IPBM to NET imaging in the heart. Methods: The NET affinity and selectivity were measured from the ability to displace specific [{sup 3}H]nisoxetine and (S,S)-[{sup 125}I]IPBM binding to rat heart membrane, respectively. To evaluate the distribution of (S,S)-[{sup 125}I]IPBM in vivo, biodistribution experiment was performed in rats. With the use of several monoamine transporter binding agents, pharmacological blocking experiments were performed in rats. Results: In vitro binding assays showed that the affinity of (S,S)-IPBM to NET was similar to those of the well-known NET-specific binding agents, nisoxetine and desipramine. Furthermore, (S,S)-[{sup 125}I]IPBM binding was inhibited by nisoxetine and desipramine, but not by dopamine or serotonin transporter binding agents. These data indicated that (S,S)-IPBM had high affinity and selectivity for NET in vitro. Biodistribution studies in rats showed rapid and high uptake of (S,S)-[{sup 125}I]IPBM by the heart and rapid clearance from the blood. The heart-to-blood ratio was 31.9 at 180 min after the injection. The administration of nisoxetine and desipramine decreased (S,S)-[{sup 125}I]IPBM accumulation in the heart, but injection of fluoxetine and GBR12909 had little influence. Conclusions: Radioiodinated (S,S)-IPBM is a potential radioligand for NET imaging in the heart.

  1. Dose selection for radioiodine therapy of borderline hyperthyroid patients with multifocal and disseminated autonomy on the basis of {sup 99m}Tc-pertechnetate thyroid uptake

    Energy Technology Data Exchange (ETDEWEB)

    Reinhardt, Michael J.; Mallek, Dirk von; Manka-Waluch, Agnieszka; Palmedo, Holger [Department of Nuclear Medicine, University Hospital Bonn (Germany); Joe, Alexius; Zimmerlin, Martina [Department of Nuclear Medicine, University Hospital Freiburg (Germany); Krause, Thomas M. [Department of Nuclear Medicine, Inselspital Bern (Switzerland)


    The aim of this study was to optimise radioiodine therapy of diffuse and nodular toxic goitre by calculation of the radiation dose delivered to the thyroid on the basis of the pretreatment technetium-99m pertechnetate thyroid uptake under thyrotropin suppression (TcTU{sub s}). The TcTU{sub s} value serves as a substitute for the non-suppressible iodine turnover and the functional autonomous mass. Marinelli's formula was used to calculate tissue absorbed doses of 150 Gy, 200 Gy, 250 Gy and 300 Gy to the thyroids of 438 patients with multifocal and disseminated autonomy. The mean age of patients was 70{+-}9 years, and the mean thyroid volume was 54{+-}26 ml. Two hundred and sixty-one of the patients had at least one documented previous episode of overt hyperthyroidism. Tissue absorbed doses were adapted to the pretreatment TcTU{sub s}: 150 Gy for a TcTU{sub s} of 1.5%-2.49%, 200 Gy for a TcTU{sub s} of 2.5%-3.49%, 250 Gy for a TcTU{sub s} of 3.5%-4.49% and 300 Gy for a TcTU{sub s} of {>=}4.5%. Normalisation of TcTU{sub s} and thyrotropin (TSH), thyroid volume reduction and frequency of hypothyroidism and recurrent hyperthyroidism were evaluated 1 year after a single radioiodine therapy. The presented dose strategy resulted in normalisation of TcTU{sub s} in 96% and an increase in TSH to the normal range in 92%. Recurrent hyperthyroidism was observed in only five patients. Thyroid volume decreased from 54{+-}26 before treatment to 34{+-}20 ml, a mean reduction of 37%. The frequency of hypothyroidism, at 0.9%, was encouragingly low. Dose selection in accordance with pretreatment TcTU{sub s} can be recommended for elimination of functional autonomous tissue with a single radioiodine therapy in patients of advanced age with enlarged thyroid glands and relevant autonomous masses who are at risk of developing iodine-induced hyperthyroidism. (orig.)

  2. Aplicaciones clínicas del radioyodo 131 (I131 en las enfermedades del tiroides Clinical applications of radioiodine 131 (I131 in the thyroid diseases

    Directory of Open Access Journals (Sweden)

    Levi González Rivero


    Full Text Available El radioyodo 131 es un isótopo radioactivo que se emplea exitosamente en el diagnóstico y tratamiento de las enfermedades benignas y malignas del tiroides. Su propiedad de integrarse selectivamente al metabolismo del tiroides y emitir una señal, le permite describir el funcionamiento glandular mediante estudios de captación, y delimitar la morfología y localización de los tejidos que capten yodo, a través de la gammagrafía. Es además una radioterapia sencilla, segura y coste-efectiva, usada como primera línea terapéutica en el control del hipertiroidismo, cuya dosis y momento de aplicación debería individualizarse según la etiología y la clínica de cada paciente. El radioyodo 131 ofrece una alternativa eficaz para reducir el tamaño del bocio no tóxico; además, respalda el tratamiento quirúrgico del carcinoma diferenciado del tiroides, y destruye a dosis ablativa los restos tisulares y las lesiones metastásicas que puede identificar durante el seguimiento gammagráfico. El empleo de radioyodo 131 está sujeto al cumplimiento de regulaciones de protección contra la radioactividad.Radioiodine 131 is a radioactive isotope that is successfully used for the diagnosis and the treatment of benign and malignant thyroid diseases. Its quality of selectively integrating to the thyroid metabolism and emitting a signal allows it to describe the gland functioning through capture studies, and to delimit the morphology and location of the tissues that capture iodine by means of gammagraphy. It is also a simple, safe and cost-effective radiotherapy used as first-line therapeutics in the control of hyperthyroidism. The dose and right time of application should be individualized according to the etiology and the clinic of each patient. Radioiodine 131 offers an efficient alternative to reduce the size of non-toxic goiter in addition to supporting the surgical treatment of the differentiated thyroid carcinoma and destroying with ablative doses

  3. Chemical composition of drinking water as a possible environment-specific factor modifying the thyroid risk in the areas subjected to radioiodine contamination (United States)

    Kolmykova, Lyudmila; Korobova, Elena; Ryzhenko, Boris


    Water is one of the main natural agents providing chemical elements' migration in the environment and food chains. In our opinion a study of spatial variation of the essential trace elements in local drinking water is worth considering as the factor that may contribute to variation of the health risk in areas contaminated by radionuclides and radioiodine in particular. Radioiodine was proved to increase the risk of thyroid cancer among children who lived in areas contaminated during the Chernobyl accident. It was also shown that low stable iodine status of the contaminated area and population also contributed to the risk of this disease in case of radionuclide contamination. The goal of the study was to investigate chemical composition of the drinking water in rural settlements of the Bryansk oblast' subjected to radioiodine contamination and to evaluate speciation of stable I and Se on the basis of their total concentration and chemical composition of the real water samples with the help of thermodynamic modelling. Water samples were collected from different aquifers discharging at different depths (dug wells, local private bore holes and water pipes) in rural settlements located in areas with contrasting soil iodine status. Thermodynamic modelling was performed using original software (HCh code of Y.Shvarov, Moscow State University, RUSSIA) incorporating the measured pH, Corg and elements' concentration values. Performed modelling showed possibility of formation of complex CaI+ ion in aqueous phase, I sorption by goethite and transfer of Se to solid phase as FeSe in the observed pH-Eh conditions. It helped to identify environmental conditions providing high I and Se mobility and their depletion from natural waters. Both the experimental data and modeling showed that I and Se migration and deficiency in natural water is closely connected to pH, Eh conditions and the concentration of typomorphic chemical elements (Ca, Mg, Fe) defining the class of water migration

  4. Evaluation of Discordance in Differentiated Thyroid Cancer Patients with Negative Radioiodine Scans and Positive Thyroglobulin Values at the Ablation Outcome Control

    Directory of Open Access Journals (Sweden)

    Zeynep Gözde Özkan


    Full Text Available Objective: We aimed to evaluate the discordance of 5 mCi (185 MBq I-131 whole body scan (WBS and thyroglobulin (Tg values at the ablation outcome control in differentiated thyroid cancer (DTC patients who had thyroidectomy and then received radioiodine (RAI ablation. Materials and Methods: We retrospectively evaluated 36 DTC patients who had RAI treatment in our department between 1992-2009 and whose 5 mCi (185 MBq I-131 WBS were negative, but Tg values were ≥2 ng/ml during the ablation outcome control (Patient group. Thirty-six patients whose Tg values were 2 cm (p2 cm (p40 (p<0.01 were significantly different between lymph node and micrometastatic groups.Conclusion: I-131 WBS/Tg level discordance at the ablation outcome control is mainly caused by metastatic lymph nodes.

  5. Iodine kinetics and dosimetry in the salivary glands during repeated courses of radioiodine therapy for thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Liu, B.; Huang, R.; Kuang, A.; Zhao, Z.; Zeng, Y.; Wang, J.; Tian, R. [Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041 (China)


    Purpose: The present study was conducted to investigate salivary iodine kinetics and dosimetry during repeated courses of radioiodine ({sup 131}I) therapy for differentiated thyroid cancer (DTC). Such data could provide a better understanding of the mechanisms of {sup 131}I induced salivary toxicity and help to develop appropriate methods to reduce this injury. Methods: Seventy-eight consecutive DTC patients (mean age 45 {+-} 17 years, 60%, female) undergoing {sup 131}I therapy for remnant ablation or metastatic tumors were prospectively recruited. Planar quantitative scintigraphy of head-neck images was serially acquired after administration of 2.9-7.4 GBq of {sup 131}I to assess kinetics in the salivary glands of patients. Salivary absorbed doses were calculated based on the schema of Medical Internal Radiation Dosimetry. Results: The maximum uptakes in percentage of administered {sup 131}I activity per kilogram of gland tissue (%/kg) were 12.9% {+-} 6.5%/kg (range, 0.4%-37.3%/kg) and 12.3% {+-} 6.2%/kg (range, 0.4%-35.1%/kg) for the parotid and submandibular glands, respectively. Statistically significant correlations of maximum uptake versus cumulative activity (r = -0.74, P < 0.01, for the parotid glands; r = -0.71, P < 0.01, for the submandibular glands) and treatment cycle (P < 0.001, for both gland types) were found. The effective half-lives of {sup 131}I in the parotid and submandibular glands were 9.3 {+-} 3.5 h (range, 1.5-19.8 h) and 8.6 {+-} 3.2 h (range, 0.8-18.0 h), respectively. A statistically significant correlation was observed between effective half-life with cumulative activity (r = 0.37, P < 0.01) and treatment cycle (P = 0.03) only for the parotid glands. The calculated absorbed doses were 0.20 {+-} 0.10 mGy/MBq (range, 0.01-0.92 mGy/MBq) and 0.25 {+-} 0.09 mGy/MBq (range, 0.01-1.52 mGy/MBq) for the parotid and submandibular glands, respectively. The photon contribution to the salivary absorbed dose was minimal in relation to the beta dose

  6. Detection system qualification for direct measurement of thyroid internal contamination by radioiodine; Qualificazione di un sistema di rilevazione trasportabile per misure dirette di contaminazione interna di radioiodio

    Energy Technology Data Exchange (ETDEWEB)

    Tiberi, V.; Battisti, P.; Gualdrini, G. [ENEA, Centro Ricerche Ezio Clementel, Bologna (Italy). Dipt. Ambiente


    The work deals with a detection system qualification for direct measurements of thyroid internal contamination by radioiodine. The isotopes {sup 131}I and {sup 125}I are the most frequently used in nuclear medicine. Because of their volatility they are very dangerous for thyroid contamination by inhalation. The system has been projected to be easily and fast used and above all transportable where the control is necessary. These characteristic make it able to realise supervision programs of internal contamination by radioiodine. In fact due the very high control frequencies (each 15 days for {sup 131}I), these programs are usually very expensive and demanding when they are executed in external measurement laboratories. The following steps are described: devices presentation, calculation of energy and efficiency parameters, minimum detectable activity, time system reliability, best operative conditions in the measurements. At the end an application example of the system is reported. [Italian] Il presente lavoro consiste nella qualificazione di un sistema di rivelazione per misure dirette di contaminazione interna da radioiodio in tiroide, progettato per essere maneggevole, di semplice e rapido impiego e trasportabile sul luogo dove e' richiesta la misura. Il sistema e' stato studiato per la realizzazione di programmi di sorveglianza della contaminazione interna da radioiodio che, richiedendo frequenze di controllo elevate (quindicinali per lo {sup 131}I), sono estremamente impegnativi ed onerosi, soprattutto se i controlli vengono effettuati in centri di misura esterni. Dopo la determinazione dei parametri della calibrazione in energia ed efficienza, la minima attivita' rivelabile, l'affidabilita' del sistema nel tempo e le condizioni operative ottimali da adottare in sede di misura, viene verificata la piena affidabilita' del sistema in un programma di sorveglianza della contaminazione interna da radioiodio.

  7. Comparison of urine iodine/creatinine ratio between patients following stringent and less stringent low iodine diet for radioiodine remnant ablation of thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Roh, Jee Ho; Kim, Byung Il; Ha, Ji Su; Chang, Sei Joong; Shin, Hye Young; Choi, Joon Hyuk; Kim, Do Min; Kim, Chong Soon [Hanil Hospital, Seoul (Korea, Republic of)


    A low iodine diet (LID) for 1 {approx} 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 tatio (urine I/Cr). 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 1 week and less stringent LID for 2 weeks, then measured their urine I/Cr ratio with spot urine when patients were admitted to the hospital. 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 {+-} 78.52 {mu} g/g in stringent LID for 1 week, and 289.75 {+-} 188.24 {mu} g/g in less stringent LID for 2 weeks. It was significantly lower in stringent LID for 1 week group ({rho} = 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. 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.

  8. Favorable Outcome of Hurthle Cell Carcinoma of the Thyroid Treated With Total Thyroidectomy, Radioiodine, and Selective Use of External-Beam Radiotherapy. (United States)

    Zavitsanos, Peter; Amdur, Robert J; Drew, Peter A; Cusi, Kenneth; Werning, John W; Morris, Christopher G


    There is controversy about the prognosis of Hurthle cell carcinoma of the thyroid. The purpose of this project is to report the outcome of a well-defined group of patients treated at a single institution in the modern era. Sixteen patients met the following inclusion criteria: Treatment with curative intent at our institution between January 1, 1997, and December 31, 2010. Primary treatment with total thyroidectomy with or without neck dissection. Age >18 years at the time of thyroidectomy. Confirmation by a pathologist of the diagnosis of a primary Hurthle cell carcinoma of the thyroid based on ≥75% Hurthle cells with extension through the tumor capsule. No areas of poorly differentiated (insular) or undifferentiated (anaplastic) carcinoma. Stage T1-3, NX-1b, M0. All patients received radioiodine immediately after thyroidectomy (remnant ablation, n=14) or as adjuvant for a recurrence (n=2). External-beam radiotherapy to the neck as adjuvant therapy after thyroidectomy was used in 2 patients and after resection of a neck recurrence in 1 patient. Five-year actuarial rates with a median 6 years of follow up on surviving patients were as follows:Overall and cancer-specific survival: 92% (1 death from Hurthle cell carcinoma). Relapse-free survival (no visible tumor and unstimulated thyroglobulin ≤1.0): 65%. Our experience suggests that the outcome of Hurthle cell carcinoma of the thyroid is favorable in adults with stage T1-3 NX-1b M0 disease who are managed with total thyroidectomy, radioiodine, and-in selected cases-external-beam radiotherapy. We do not have the ability to compare our results to other management strategies.

  9. Dose selection for radioiodine therapy of borderline hyperthyroid patients according to thyroid uptake of {sup 99m}Tc-pertechnetate: applicability to unifocal thyroid autonomy?

    Energy Technology Data Exchange (ETDEWEB)

    Reinhardt, Michael J.; Joe, Alexius Y. [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); University Hospital Freiburg, Department of Nuclear Medicine, Hugstetter Str. 55, 79106 Freiburg (Germany); Biermann, Kim; Brockmann, Holger; Mallek, Dirk von; Ezziddin, Samer [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Wissmeyer, Michael [Inselspital Bern, Department of Nuclear Medicine, 3010 Bern (Switzerland); Juengling, Freimut D.; Krause, Thomas M. [University Hospital Freiburg, Department of Nuclear Medicine, Hugstetter Str. 55, 79106 Freiburg (Germany); Inselspital Bern, Department of Nuclear Medicine, 3010 Bern (Switzerland)


    The aim of this study was to evaluate the feasibility of applying a previously described dose strategy based on {sup 99m}Tc-pertechnetate thyroid uptake under thyrotropin suppression (TcTU{sub s}) to radioiodine therapy for unifocal thyroid autonomy. A total of 425 consecutive patients (302 females, 123 males; age 63.1{+-}10.3 years) with unifocal thyroid autonomy were treated at three different centres with {sup 131}I, using Marinelli's formula for calculation of three different absorbed dose schedules: 100-300 Gy to the total thyroid volume according to the pre-treatment TcTU{sub s} (n=146), 300 Gy to the nodule volume (n=137) and 400 Gy to the nodule volume (n=142). Successful elimination of functional thyroid autonomy with either euthyroidism or hypothyroidism occurred at a mean of 12 months after radioiodine therapy in 94.5% of patients receiving 100-300 Gy to the thyroid volume, in 89.8% of patients receiving 300 Gy to the nodule volume and in 94.4% receiving 400 Gy to the nodule volume. Reduction in thyroid volume was highest for the 100-300 Gy per thyroid and 400 Gy per nodule strategies (36{+-}19% and 38{+-}20%, respectively) and significantly lower for the 300 Gy per nodule strategy (28{+-}16%; p<0.01). A dose strategy based on the TcTU{sub s} can be used independently of the scintigraphic pattern of functional autonomous tissue in the thyroid. (orig.)

  10. Is there a role for unstimulated thyroglobulin velocity in predicting recurrence in papillary thyroid carcinoma patients with detectable thyroglobulin after radioiodine ablation? (United States)

    Wong, Hilda; Wong, Kai P; Yau, Thomas; Tang, Vikki; Leung, Roland; Chiu, Joanne; Lang, Brian Hung-Hin


    In the follow-up of papillary thyroid cancer (PTC) patients treated with curative thyroidectomy and radioiodine ablation, raised thyroglobulin (Tg) predicts recurrence with reasonable sensitivity and specificity. However, a proportion of patients present with raised Tg level but no other clinical evidence of disease. Only limited data on Tg kinetics have been reported to date. Here we aim to evaluate the prognostic and predictive significance of nonstimulated serum Tg velocity (TgV). Consecutive PTC patients treated with curative thyroidectomy and radioiodine ablation between 2003 and 2010 were analyzed. Patients with at least one detectable Tg measurement (>0.2 ng/mL) were included. TgV was defined as the annualized rate of Tg change. Logistic regression analyses were performed to evaluate the role of TgV in the prediction of disease recurrence. The optimal TgV cutoff was assigned by receiver-operating characteristic curve analysis. Overall survival of patients above versus below the TgV cutoff were determined by the Kaplan-Meier method and compared. Of a total of 501 patients, 87 had at least one Tg value >0.2 ng/mL; in these latter patients, 29 (33.3%) developed recurrence. TgV was an independent predictor of the recurrence. TgV ≥0.3 ng/mL per year predicted recurrence with a sensitivity of 83.3% and specificity of 94.4%. Patients with TgV below the cutoff had a significantly better overall survival (p = 0.038). TgV predicts recurrence with high sensitivity and specificity, and is a prognosticator of survival in postthyroidectomy and postablation PTC patients with raised Tg.

  11. Results of preventive radioiodine therapy in euthyroid patients with history of hyperthyroidism prior to administration of amiodarone with permanent atrial fibrillation--a preliminary study. (United States)

    Czarnywojtek, Agata; Zgorzalewicz-Stachowiak, Małgorzata; Woliński, Kosma; Płazińska, Maria Teresa; Miechowicz, Izabela; Kwiecińska, Barbara; Czepczyński, Rafał; Królicki, Leszek; Ruchała, Marek


    Radioiodine (RAI) therapy is a standard procedure in the treatment of hyperthyroidism. However, the use of RAI in euthyroid patients requiring chronic administration of amiodarone (AM) where other antiarrhythmic drugs may lack efficacy is still controversial. The aim of this study was to assess the safety and efficacy of an AM therapy prior to treatment with radioiodine therapy in euthyroid patients with permanent atrial fibrillation (PAF), who had been treated for hyperthyroidism in the past. This was a retrospective observational study. Patients were assessed at baseline and two, six, eight, and 12 months after RAI therapy. 17 euthyroid patients with PAF were qualified to the RAI (female/male 3/14; age range 65 to 87, median 71). The patients required chronic administration of AM as a prophylaxis against sudden death. Each patient received an ablative dose of 800 MBq (22 mCi) of 131I. At baseline and during follow-up, no side effects of the therapy and no signs of drug intolerance were observed. Subclinical hyperthyroidism occurred in two (11.8%) cases after two months of RAI and five weeks of AM administration. In this situation, RAI therapy was repeated. Three patients (17.6%) after six months, and another two (11.8%) after eight months, required an additional dose of 131I due to amiodarone-induced thyrotoxicosis (AIT). Twelve patients (70.6%) returned to spontaneous sinus rhythm within two months. Fourteen patients (82.4%) had sinus rhythm during follow-up after six and 12 months of treatment. Preventive RAI in euthyroid (but previously hyperthyroid) patients with PAF before administration of AM may be the method of choice. This is particularly important for patients who will require permanent AM administration as a life-saving drug.

  12. Radioiodine therapy in veterinary medicine: treatment of hyperthyroidism in a cat; Die Radioiodtherapie in der Veterinaermedizin: Behandlung der Schilddruesenueberfunktion bei einer Katze

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    Reinartz, P.; Sabri, O.; Zimny, M.; Buell, U. [Technische Hochschule Aachen (Germany). Klinik fuer Nuklearmedizin; Kinzel, S.; Kuepper, W. [Technische Hochschule Aachen (Germany). Inst. fuer Versuchstierkunde; Bachmann, T. [Tierarztpraxis Dr. med. vet. Thomas Bachmann, Glashhuetten (Germany)


    A nine-year-old cat with symptoms of a distinct hyperthyroidism was presented at the University Hospital of the RWTH Aachen. The clinical symptoms as well as the diagnostic procedures performed at the hospital confirmed the diagnosis. After five weeks of thyreostatic medication a regular metabolism of the thyroid gland was established, followed by a radioiodine therapy with 70.3 MBq 131-iodine. Subsequently, the cat was hospitalized for two days before it could be released in good condition. Six weeks after treatment the former drastically reduced weight of the cat recovered to near normal. Even though the chemical analysis detected a discrete hyperthyroidism, clinical symptoms were no longer prominent. Three months after treatment, the final examination showed a regular metabolism of the thyroid gland without a specific thyroidal medication. The presented case illustrates that radioiodine therapy is a safe and efficient treatment of thyroidal dysfunctions in veterinary medicine. (orig.) [Deutsch] Eine neun Jahre alte, europaeische Langhaarkatze wurde mit Symptomen einer ausgepraegten Schilddruesenueberfunktion im Universitaetsklinikum der RWTH Aachen vorgestellt. Sowohl die klinische Symptomatik als auch die Labordiagnostik und die apparativ erhobenen Befunde belegten das Vorliegen einer Hyperthyreose. Im Anschluss an eine fuenfwoechige thyreostatische Therapie, mit der eine euthyreote Stoffwechsellage erreicht werden konnte, wurde eine Radioiodtherapie mit 70,3 MBq 131-Iod durchgefuehrt. Nach einer nur zweitaegigen komplikationslosen Hospitalisierung konnte die Katze in gutem Allgemeinzustand entlassen werden. Sechs Wochen nach der Therapie hatte sich das zuvor deutlich reduzierte Koerpergewicht auf nahezu normgerechte Werte erhoeht; klinische Symptome der Schilddruesenueberfunktion liessen sich trotz einer laborchemisch diagnostizierten diskreten Gesamtthyroxiderhoehung nicht mehr nachweisen. Bei einer abschliessenden Kontrolle drei Monate nach Entlassung wies

  13. Development of radioiodinated ligands for exploration of brain monoamine oxidase by tomo-scintigraphy; Developpement de ligands radioactifs pour l'exploration des monoamines oxydases cerebrales en tomoscintigraphie

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    Rafii, H


    Monoamine oxidases, MAO, are important in the regulation of monoaminergic neuro-transmissions. The fluctuations in MAO activities has been observed in some psychiatric and neuro-degenerative diseases. Thus, quantification of cerebral MAO activity would be useful for diagnosis and the therapeutic follow-up of these disorders. With the object of doing an in vivo scintigraphic exploration of cerebral MAO by SPECT, we have undertaken to synthesize some radioiodinated MAO inhibitors. In the first part of this work, we have discussed the general properties of the monoamine oxidases and their inhibitors. In the second part we have described the scintigraphic methods. the ligands to be used for MAO exploration, and the radioiodination methods. At last in the third part, the development of three radioiodinated ligands has been presented: - [{sup 125}I]3-iodopargyline. In vivo results showed that, this radioligand blocked the cerebral MAO-B with moderate selectivity. However, complementary in vivo studies would be needed to define precisely its activity.- [{sup 125}I]Ro 16-6491. The cerebral fixation of this radioligand was in accordance with the MAO-B sites in the rat brains, but its fixation was too low for scintigraphic exploration in vivo with iodine-123. - [{sup 125}I]Ro 11-9900. In vivo studies of rat brains showed that the MAO-A sites were bound preferentially by this radioligand. The cerebral biodistribution of this ligand labelled with iodine-123 is considered for use in a model animal nearest to human pathology. (author)

  14. Seasonal variability of iodine and selenium in surface and groundwater as a factor that may contribute to iodine isotope balance in the thyroid gland and its irradiation in case of radioiodine contamination during accidents at the NPP (United States)

    Korobova, Elena; Kolmykova, Lyudmila; Ryzhenko, Boris; Berezkin, Viktor; Saraeva, Anastasia


    Radioiodine release to the environment during the accident at the Chernobyl NPP led to the increased risk of the thyroid cancer cases within the contaminated areas, the effect being aggravated in conditions of stable iodine and selenium deficiency in local food chains. Although the drinking water iodine is usually believed to contribute not more than 10% to local diet, our estimations accounting of water content in other products and several regional studies (e.g. India and Australia) proved its portion to be at least twice as much. As radioiodine isotopes are short-lived, their absorption depends greatly on stable iodine and selenium sufficiency in thyroid gland in the first few days of contamination and seasonal variation of stable iodine and selenium in local sources of drinking water may be significant as modifying the resulting thyroid irradiation in different seasons of the year. The main goal of the study was to evaluate seasonal variation of levels of iodine and selenium in natural waters of the Bryansk region as a possible factor affecting the radioiodine intake by thyroid gland of animals and humans in case of radioiodine contamination during the accident. Seasonal I and Se concentration was measured in the years of 2014 and 2015 at 14 test points characterizing surface (river and lake) and drinking groundwater. Obtained data proved considerable seasonal variation of I and Se concentration in natural waters (3,7-8,1 μg/l and 0,04-0,4 μg/l respectively) related to physico-chemical water parameters, such as pH, Eh and fluctuations in concentration of dissolved organic matter. The widest I and Se seasonal variability was observed in surface and well waters, maximum I level being found in autumn at the end of vegetation period characterized by active I leaching from the decomposed organic residues by long lasting precipitations. The content of selenium in the surface waters during summer-autumn (0,06-0,3 μg/l) was higher than in spring (0,04-0,05

  15. The influence of saliva flow stimulation on the absorbed radiation dose to the salivary glands during radioiodine therapy of thyroid cancer using {sup 124}I PET(/CT) imaging

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    Jentzen, Walter; Schmitz, Jochen; Freudenberg, Lutz; Eising, Ernst; Bockisch, Andreas; Stahl, Alexander [Universitaet Duisburg-Essen, Klinik fuer Nuklearmedizin, Essen (Germany); Balschuweit, Dorothee; Hilbel, Thomas [Fachhochschule Gelsenkirchen, Fachbereich Physikalische Technik, Gelsenkirchen (Germany)


    A serious side effect of high-activity radioiodine therapy in the treatment of differentiated thyroid cancer is radiogenic salivary gland damage. This damage may be diminished by lemon-juice-induced saliva flow immediately after {sup 131}I administration. The aim of this study was to assess the effect of chewing lemon slices on the absorbed (radiation) doses to the salivary glands. Ten patients received (pretherapy) {sup 124}I PET(/CT) dosimetry before their first radioiodine therapy. The patients underwent a series of six PET scans at 0.5, 1, 2, 4, 48 and {>=}96 h and one PET/CT scan at 24 h after administration of 27 MBq {sup 124}I. Blood samples were also collected at about 2, 4, 24, 48, and 96 h. Contrary to the standard radioiodine therapy protocol, the patients were not stimulated with lemon juice. Specifically, the patients chewed no lemon slices during the pretherapy procedure and neither ate food nor drank fluids until after completion of the last PET scan on the first day. Organ absorbed doses per administered {sup 131}I activity (ODpAs) as well as gland and blood uptake curves were determined and compared with published data from a control patient group, i.e. stimulated per the standard radioiodine therapy protocol. The calculations for both groups used the same methodology. A within-group comparison showed that the mean ODpA for the submandibular glands was not significantly different from that for the parotid glands. An intergroup comparison showed that the mean ODpA in the nonstimulation group averaged over both gland types was reduced by 28% compared to the mean ODpA in the stimulation group (p=0.01). Within each gland type, the mean ODpA reductions in the nonstimulation group were statistically significant for the parotid glands (p=0.03) but not for the submandibular glands (p=0.23). The observed ODpAs were higher in the stimulation group because of increased initial gland uptake rather than group differences in blood kinetics. The {sup 124}I PET

  16. Prevalence and degree of thyroid pathology in hyperthyroid cats increases with disease duration: a cross-sectional analysis of 2096 cats referred for radioiodine therapy. (United States)

    Peterson, Mark E; Broome, Michael R; Rishniw, Mark


    Hyperthyroidism is common in cats, but there are no reports that evaluate its severity or underlying thyroid tumor disease based on disease duration (ie, time from original diagnosis). The objective of this study was to compare serum thyroxine (T4) concentrations and thyroid scintigraphic characteristics of cats referred for radioiodine treatment based on disease duration. This was a cross-sectional study of 2096 cats with hyperthyroidism. Cats were divided into five groups based on time from diagnosis: ⩽1 year (n = 1773); >1-2 years (n = 169); >2-3 years (n = 88); >3-4 years (n = 35); and >4-6.1 years (n = 31). Methimazole, administered to 996 (47.5%) cats, was stopped at least 1 week prior to examination to allow for serum T4 testing. Each thyroid scintiscan was evaluated for pattern (unilateral, bilateral, multifocal), location (cervical, thoracic inlet, chest) and size (small, medium, large, huge) of the thyroid tumor, as well as features suggesting malignancy. Median serum T4 concentration increased with increasing disease duration from 100 nmol/l (⩽1 year) to 315 nmol/l (>4-6.1 years) (P disease decreased, whereas multifocal disease (three or more tumor nodules) increased (P disease duration. Median tumor volume in the five groups increased from 1.6 cm(3) (⩽1 year) to 6.4 cm(3) (>4-6.1 years). Prevalence of large (4-8 cm(3)) and huge (>8 cm(3)) thyroid tumors increased from 5.1% (⩽1 year) to 88.6% (>4-6.1 years), while the prevalence of intrathoracic tumor tissue increased from 3.4% (⩽1 year) to 32.3% (>4-6.1 years). Prevalence of suspected thyroid carcinoma (characterized by severe hyperthyroidism; huge, intrathoracic, multifocal tumors; refractory to methimazole treatment) increased with increasing disease duration from 0.4% (⩽1 year) to 19.3% (>4-6.1 years). Our results indicate that the prevalence of severe hyperthyroidism, large thyroid tumors, multifocal disease, intrathoracic thyroid masses and suspected malignant disease all increase with

  17. Radioiodinated fatty acid carnitine ester: synthesis and biodistribution of 15-(p-iodo(/sup 131/I)-phenyl)pentadecanoyl-D,L-carnitine chloride

    Energy Technology Data Exchange (ETDEWEB)

    Eisenhut, M.; Liefhold, J.

    After the uptake into heart muscle cells long chain fatty acids enter predominantly into the triglyceride and phospholipid pool before they are degraded in the mitochondria by ..beta..-oxidation. Therefore the formation of fatty acid esters with glycerine obscures the functional ability of the heart namely to catabolize free fatty acids. The sum of the two reaction pathways are visualized by sequential heart scintigraphy with e.g. /sup 131/I labeled 15-(p-iodo-phenyl)-pentadecanoic acid (IPPA). Before the fatty acids can be degraded by ..beta..-oxidation they are bound to carnitine for mitochondrial membrane transport. Thus IPPA would not participate in lipid formation, if it is offered as 15-(p-iodo(/sup 131/I)-phenyl)-pentadecanoyl-D,L-carnitine chloride (IPPA-CE) to the heart muscle cells. Additionally carnitine esters of fatty acids are known to be better substrates for ..beta..-oxidation than free fatty acids. We were therefore interested in the biochemical fate of radioiodinated IPPA-CE in rats.

  18. Aerosol residence times and changes in radioiodine-131I and radiocaesium-137 Cs activity over Central Poland after the Fukushima-Daiichi Nuclear reactor accident. (United States)

    Długosz-Lisiecka, Magdalena; Bem, Henryk


    The first detectable activities of radioiodine (131)I, and radiocaesium (134)Cs and (137)Cs in the air over Central Poland were measured in dust samples collected by the ASS-500 station in the period of 21(st) to 24(th) of March, 2011. However, the highest activity of both fission products, (131)I and (137)Cs: 8.3 mBq m(-3) and 0.75 mBq m(-3), respectively, were obtained in the samples collected on 30(th) March, i.e.∼18 days after the beginning of the fission products' discharge from the damaged units of the Fukushima Daiichi Nuclear Power Plant. The simultaneously determined corrected aerosol residence time for the same samples by (210)Pb/(210)Bi and (210)Pb/(210)Po methods was equal to 10 days. Additionally, on the basis of the activity ratio of two other natural cosmogenic radionuclides, (7)Be and (22)Na in these aerosol samples, it was possible to estimate the aerosol residence time at ∼150 days for the solid particles coming from the stratospheric fallout. These data, as well as the differences in the activity size distribution of (7)Be and (131)I in the air particulate matter, show, in contrast to the Chernobyl discharge, a negligible input of stratospheric transport of Fukushima-released fission products.

  19. Guideline on radiation protection in medicine requires documentation of radioiodine therapy and follow-up. What are the benefits of an electronic database?

    Energy Technology Data Exchange (ETDEWEB)

    Koch, W.; Rosa, F.; Knesewitsch, P.; Hahn, K. [Klinik und Poliklinik fuer Nuklearmedizin der LMU Muenchen (Germany)


    The lately updated German guideline on radiation protection in medicine (Richtlinie Strahlenschutz in der Medizin) requires the physician who administers radioactive substances for therapy, to perform and document follows-up. In order to decrease the administrative burden, an electronic database was developed that interfaces with a word processing software to generate written reports and statistic analysis. Methods: Based on Microsoft {sup registered} Access and Microsoft {sup registered} Visual Basic a database was created to monitor patients with benign and malignant thyroid disorders after radioiodine therapy. It permits automatic creation of therapy documents and necessary patient reports in Microsoft {sup registered} Word. Intuitive handling, third level of normalization in database architecture and automatic plausibility checks guarantee integrity of the data and the efficacy of the database. Results, conclusion: The new software has been a success in over 1500 patients and over 3800 in- and outpatient therapies and visits. The effort of data entry is easily offset by the automatic generation of the necessary patient reports. The required supervision of the follow-up appointments is now also user-friendly and efficient. (orig.)

  20. A Case of Thyroid Papillary Carcinoma: Remarkable Decrease in Multiple Lung Metastases within 40 Years after a Single Administration of Radioiodine without Thyroidectomy and with Later Anaplastic Transformation

    Directory of Open Access Journals (Sweden)

    Chio Okuyama


    Full Text Available Differentiated thyroid carcinoma is an uncommon malignancy of childhood and adolescence that is unique because it has an overall favorable prognosis despite its relatively high rate of nodal and distant metastases. Total thyroidectomy and positive 131I therapy are recommended for cases with pulmonary metastases. In contrast, anaplastic thyroid cancer is one of the most aggressive malignancies that have an unfavorable and miserable prognosis. We report a case with an impressively long history. The patient had multiple pulmonary metastases that had been diagnosed by 131I administration when he was 14 years old, about 45 years before he underwent thyroidectomy. He had been kept unaware of his disease by his family and received no treatment for most of his life. Pulmonary nodules were noted at several medical checkups and showed a remarkable decrease in size during the untreated 44-year period after the 131I administration. At age 58, his thyroid cancer was first detected and total thyroidectomy was performed, with subsequent radioiodine therapy for pulmonary metastases. Unfortunately, anaplastic carcinoma developed and he died of disseminated tumors later.

  1. Site-specific/stable radioiodination of 1,2-Pal-3-IPPA: an agent for the potential clinical evaluation of pancreatic insufficiency by urine analysis. (United States)

    Knapp, F F; Kropp, J; McPherson, D W; Ambrose, K R; Lambert, C R; Callahan, A P; Kirsch, G; Biersack, H J


    To measure pancreatic lipase activity, we synthesized a triglyceride containing a radioiodinated fatty acid. The urinary excretion of radioactivity was measured in five rats following administration of the agent by feeding tube. We attached 15-phenylpentadecanoic acid (PPA) to position-3 of 1,2-dipalmitoyl-rac-glycerol (1,2-Pal) to form 1,2-Pal-3-PPA. The 1,2-Pal-3-IPPA (expected lipase substrate) was prepared by the thallation-iodide displacement method. In a dual-label study, the 125I-1,2-Pal-3-IPPA triglyceride was administered with the 131I-IPPA free acid to rats (n = 5) by oral gavage. Urine and feces were collected daily and the tissue distribution of both tracers was evaluated over a five-day period. A significant portion of the administered activity was excreted in 24 hr in the urine (125I, 30.31% + 4.32%; 131I, 35.0% + 7.29%), which cochromatographed with hippuric acid by thin layer chromatography. Release of the acidic components from the conjugated excretory products by acid hydrolysis of the urine provided the radioactive acidic metabolites. Analysis of the Folch extracts of fat samples demonstrated that the radioactive components cochromatographed in the triglyceride region. This agent appears useful for the evaluation of various gastrointestinal diseases.

  2. Synthesis and radioiodination of di-iodo-Evan's blue via isotopic exchange reaction in the molten state and evaluation of the kinetics

    Energy Technology Data Exchange (ETDEWEB)

    El-Azony, K.M. [Research Center Juelich (Germany). Inst. of Nuclear Chemistry]|[Hot Lab. Center, Cairo (Egypt). Radioactive Isotopes and Generators Dept.; Bier, D.; Coenen, H.H. [Research Center Juelich (Germany). Inst. of Nuclear Chemistry


    Many aryl halides were synthesized from aryl amines such as iodo-trypan, iodo-methylene blue and iodo-toluidine. Methylene blue and toludine blue are phenothiazinium dyes and were used to localize parathyroid glands visually during surgery. Radioiodination of these compounds by using iodine-123 analogues for scintgraphic localization of parathyroids was reported. Radiolabelled dyes administered may also localize in tumor tissues. Evan's blue dye was used to study altered sarcolemmal permeability in dystrophic muscle fibers, and in animals to study muscular dystrophy. In this work Diiodo-Evan's blue was synthesized via Sandmeyer reaction and characterized by mass spectrum analysis. A procedure for labelling DIEB with Na{sup 131}I via isotopic exchange in molten medium was developed. The labelling conditions studied for the isotopic exchange of {sup 131}I-for-I in DIEB included the effect of temperature and solvents (melt of acetamide, benzoic and pivalic acid). Kinetic studies were performed to obtain [{sup 131}I] DIEB with more reliable reaction conditions. Quality control for the final product ([{sup 131}I] DIEB) was performed by HPLC. (orig.)

  3. Efficacy of Low-dose (2 millicurie) versus Standard-dose (4 millicurie) Radioiodine Treatment for Cats with Mild-to-Moderate Hyperthyroidism. (United States)

    Lucy, J M; Peterson, M E; Randolph, J F; Scrivani, P V; Rishniw, M; Davignon, D L; Thompson, M S; Scarlett, J M


    Radioiodine (131 I) is effective treatment for hyperthyroidism in cats, but optimal dose to restore euthyroidism without inducing hypothyroidism is unclear. Treatment-induced hypothyroidism can lead to azotemia and reduced duration of survival. To compare efficacy and short-term outcomes of low-dose 131 I versus higher, standard-dose 131 I as treatment for hyperthyroidism. A total of 189 client-owned cats undergoing 131 I treatment for mild-to-moderate hyperthyroidism (serum T4 ≥ 4.0 μg/dL and hyperthyroidism, overt hypothyroidism (low T4 , high TSH), subclinical hypothyroidism (normal T4 , high TSH), and azotemia. There was no significant difference in prevalence of cats with persistent hyperthyroidism between standard- and low-dose treatment groups at 3 (0% versus 5.3%; P = .34) and 6 (0% versus 3.3%; P = .51) months. Overt (18% versus 1%; P = .0005) or subclinical (46% versus 21%; P = .004) hypothyroidism was more common in cats at 6 months after standard-dose 131 I. No difference in incidence of azotemia existed between groups, but cats treated with standard-dose 131 I had higher creatinine concentrations (P hyperthyroidism, as evidenced by a cure rate of >95% with reduced frequency of iatrogenic hypothyroidism and azotemia. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  4. Calculation of therapeutic activity of radioiodine in Graves' disease by means of Marinelli's formula, using technetium (99mTc) scintigraphy. (United States)

    Szumowski, Piotr; Mojsak, Małgorzata; Abdelrazek, Saeid; Sykała, Monika; Amelian-Fiłonowicz, Anna; Jurgilewicz, Dorota; Myśliwiec, Janusz


    The therapeutic activity of 131I administered to patients with Graves' disease can be calculated by means of Marinelli's formula. The thyroidal iodine uptake (131IUmax) needed for the calculation is usually determined with the use of 131I. The purpose of the paper was to estimate 131IUmax on the basis of technetium uptake in the thyroid at 20 min (99mTcU20min). Eighty patients suffering from Graves' disease were qualified for radioiodine therapy with measurement of fT4, fT3, thyroid-stimulating hormone and its receptor (TRAb). Prior to the treatment, all the patients were euthyroid. 131IUmax for each patient was determined according to the levels of 131I after 24 h (131IU24h), while effective half-life (T eff) according to the measurements of 131IU24h and 131I uptake after 48 h (131IU48h). Additionally, on the day before measuring 131IU24h, 99mTcU20min was calculated for each patient. It was demonstrated that there existed a correlation, with statistical significance at p  10 IU/ml. It is possible to predict thyroid iodine uptake 131IU24h in Graves' disease on the basis of measuring the uptake of 99mTcU20min. This shortens the time necessary for diagnosis and enables the calculation of 131I activity using Marinelli's formula.

  5. Radioiodinated D-(+)-N1-ethyl-2-iodolysergic acid diethylamide: A ligand for in vitro and in vivo studies of serotonin receptors

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    Lever, J.R.; Scheffel, U.A.; Musachio, J.L.; Stathis, M.; Wagner, H.N. Jr. (Johns Hopkins Univ., Baltimore, MD (USA))


    Radioiodinated D-(+)-N1-ethyl-2-iodolysergic acid diethylamide ((125I)-EIL) has been evaluated as a ligand for in vitro and in vivo studies of cerebral serotonin 5-HT{sub 2} receptors. (125I)-EIL exhibited high affinity for 5-HT{sub 2} receptors with a high degree of specific binding in membranes from rat prefrontal cortex. The regional distribution of (125I)-EIL binding in vivo to seven areas of mouse brain correlated significantly with known densities of 5-HT{sub 2} receptors. In vivo specificity, defined by tissue to cerebellum radioactivity ratios, reached a maximum for frontal cortex at 6 hr (21.2) and persisted through 16 hr (8.8). Ketanserin, a 5-HT{sub 2} receptor antagonist, fully inhibited binding in a dose dependent fashion in all brain regions except cerebellum. By contrast, blockers for dopamine D{sub 2}, {alpha}- or {beta}-adrenergic receptors did not significantly inhibit radioligand binding in any region. (125I)-EIL selectively labels 5-HT{sub 2} receptors in vivo with the highest specificity of any serotonergic ligand reported to date, indicating that (123I)-EIL should prove applicable to single photon emission computed tomography studies in living brain.

  6. Ion-exchange separation of radioiodine and its application to production of {sup 124}I by alpha particle induced reactions on antimony

    Energy Technology Data Exchange (ETDEWEB)

    Shuza Uddin, Md. [Forschungszentrum Juelich (Germany). Inst. fuer Neurowissenschaften und Medizin, INM-5: Nuklearchemie; Atomic Energy Research Establishment, Inst. of Nuclear Science and Technology, Dhaka (Bangladesh); Qaim, Seyed M.; Spahn, Ingo; Spellerberg, Stefan; Scholten, Bernhard; Coenen, Heinz H. [Forschungszentrum Juelich (Germany). Inst. fuer Neurowissenschaften und Medizin, INM-5: Nuklearchemie; Hermanne, Alex [Vrije Univ. Brussel (Belgium). Cyclotron Lab.; Hossain, Syed Mohammod [Atomic Energy Research Establishment, Inst. of Nuclear Science and Technology, Dhaka (Bangladesh)


    The basic parameters related to radiochemical separation of iodine from tellurium and antimony by anion-exchange chromatography using the resin Amberlyst A26 were studied. The separation yield of {sup 124}I amounted to 96% and the decontamination factor from {sup 121}Te and {sup 122}Sb was > 10{sup 4}. The method was applied to the production of {sup 124}I via the {sup 123}Sb(α, 3n) reaction. In an irradiation of 110 mg of {sup nat}Sb{sub 2}O{sub 3} (thickness ∝0.08 g/cm{sup 2}) with 38 MeV α-particles at 1.2 μA beam current for 4 h, corresponding to the beam energy range of E{sub α} = 37 → 27 MeV, the batch yield of {sup 124}I obtained was 12.42 MBq and the {sup 125}I and {sup 126}I impurities amounted to 3.8% and 0.7%, respectively. The experimental batch yield of {sup 124}I amounted to 80% of the theoretically calculated value but the level of the radionuclidic impurities were in agreement with the theoretical values. About 96% of the radioiodine was in the form of iodide and the inactive impurities (Te, Sb, Sn) were below the permissible level. Due to the relatively high level of radionuclidic impurity the {sup 124}I produced would possibly be useful only for restricted local consumption or for animal experiments.

  7. Engineering of Radioiodine-Labeled Gold Core-Shell Nanoparticles As Efficient Nuclear Medicine Imaging Agents for Trafficking of Dendritic Cells. (United States)

    Lee, Sang Bong; Lee, Sang-Woo; Jeong, Shin Young; Yoon, GhilSuk; Cho, Sung Jin; Kim, Sang Kyoon; Lee, In-Kyu; Ahn, Byeong-Cheol; Lee, Jaetae; Jeon, Yong Hyun


    The development of highly sensitive, stable, and biocompatible imaging agents allowing visualization of dendritic cell (DC) migration is one of the essential factors for effective DC-based immunotherapy. Here, we used a novel and efficient synthesis approach to develop radioiodine-124-labeled tannic acid gold core-shell nanoparticles (124I-TA-Au@AuNPs) for DC labeling and in vivo tracking of their migration using positron emission tomography (PET). 124I-TA-Au@AuNPs were produced within 40 min in high yield via straightforward tannic acid-mediated radiolabeling chemistry and incorporation of Au shell, which resulted in high radio-sensitivity and excellent chemical stability of nanoparticles in DCs and living mice. 124I-TA-Au@AuNPs demonstrated good DC labeling efficiency and did not affect cell biological functions, including proliferation and phenotype marker expression. Importantly, 124I-TA-Au@AuNPs in an extremely low amount (0.1 mg/kg) were successfully applied to track the migration of DCs to lymphoid organs (draining lymph nodes) in mice.

  8. Radiopharmaceuticals to monitor the expression of transferred genes in gene transfer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, L. I. [University of Alberta, Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research


    The development and application of radiopharmaceuticals has, in many instances, been based on the pharmacological properties of therapeutic agents. The molecular biology-biotechnology revolution has had an important impact on treatment of diseases, in part through the reduced toxicity of `biologicals`, in part because of their specificity for interaction at unique molecular sites and in part because of their selective delivery to the target site. Immunotherapeutic approaches include the use of monoclonal antibodies (MABs), MAB-fragments and chemotactic peptides. Such agents currently form the basis of both diagnostic and immunotherapeutic radiopharmaceuticals. More recently, gene transfer techniques have been advanced to the point that a new molecular approach, gene therapy, has become a reality. Gene therapy offers an opportunity to attack disease at its most fundamental level. The therapeutic mechanism is based on the expression of a specific gene or genes, the product of which will invoke immunological, receptor-based or enzyme-based therapeutic modalities. Several approaches to gene therapy of cancer have been envisioned, the most clinically-advanced concepts involving the introduction of genes that will encode for molecular targets nor normally found in healthy mammalian cells. A number of gene therapy clinical trials are based on the introduction of the Herpes simplex virus type-1 (HSV-1) gene that encodes for viral thymidine kinase (tk+). Once HSV-1 tk+ is expressed in the target (cancer) cell, therapy can be effected by the administration of a highly molecularly-targeted and systemically non-toxic antiviral drug such as ganciclovir. The development of radiodiagnostic imaging in gene therapy will be reviewed, using HSV-1 tk+ and radioiodinated IVFRU as a basis for development of the theme. Molecular targets that could be exploited in gene therapy, other than tk+, will be identified

  9. Evaluation of an anti-p185{sup HER2} (scFv-C{sub H}2-C{sub H}3){sub 2} fragment following radioiodination using two different residualizing labels: SGMIB and IB-Mal-D-GEEEK

    Energy Technology Data Exchange (ETDEWEB)

    Vaidyanathan, Ganesan [Duke University Medical Center, Durham, NC 27710 (United States)], E-mail:; Jestin, Emmanuelle [Duke University Medical Center, Durham, NC 27710 (United States); Olafsen, Tove; Wu, Anna M. [Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095 (United States); Zalutsky, Michael R. [Duke University Medical Center, Durham, NC 27710 (United States)


    Introduction: A 105-kDa double mutant single-chain Fv-Fc fragment (scFv-Fc DM) derived from the anti-p185{sup HER2} hu4D5v8 antibody (trastuzumab; Herceptin) has been described recently. The goal of this study was to investigate whether improved tumor targeting could be achieved with this fragment through the use of residualizing radioiodination methods. Methods: The scFv-Fc DM fragment was radioiodinated using N-succinimidyl 4-guanidinomethyl 3-[{sup 131}I]iodobenzoate ([{sup 131}I]SGMIB) and N{sup {epsilon}}-(3-[{sup 131}I]iodobenzoyl)-Lys{sup 5}-N{sup {alpha}}- maleimido-Gly{sup 1}-GEEEK ([{sup 131}I]IB-Mal-D-GEEEK), two residualizing radioiodination agents that have been used successfully with intact antibodies. Paired-label internalization assays of the labeled fragments were performed in vitro using MCF7 human breast cancer cells transfected to express HER2 (MCF7-HER2); comparisons were made to scFv-Fc DM directly radioiodinated using Iodogen. The tissue distribution of the scFv-Fc DM labeled with [{sup 125}I]IB-Mal-D-GEEEK and [{sup 131}I]SGMIB was compared in athymic mice bearing MCF7-HER2 xenografts. Results: The scFv-Fc DM fragment was labeled with [{sup 131}I]SGMIB and [{sup 131}I]IB-Mal-D-GEEEK in conjugation yields of 53% and 25%, respectively, with preservation of immunoreactivity for HER2. Internalization assays indicated that labeling via SGMIB resulted in a 1.6- to 3.5-fold higher (P<.05) retention of radioactivity, compared to that from the directly labeled fragment, in HER2-expressing cells during a 24-h observation period. Likewise, the amount of radioactivity retained in cells from the IB-Mal-D-GEEEK-labeled fragment was 1.4- to 3.3-fold higher (P<.05). Tumor uptake of radioiodine activity in athymic mice bearing MCF7-HER2 xenografts in vivo was significantly higher for the [{sup 125}I]IB-Mal-D-GEEEK-labeled scFv-Fc DM fragment compared with that of the [{sup 131}I]SGMIB-labeled fragment, particularly at later time points. The uptake of {sup

  10. Genes and Gene Therapy (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  11. Procedure guideline for radioiodine therapy and {sup 131}iodine whole-body scintigraphy in paediatric patients with differentiated thyroid cancer; Verfahrensanweisung zur Radioiodtherapie und {sup 131}I-Ganzkoerperszintigraphie bei differenzierten Schilddruesenkarzinomen im Kindes- und Jugendalter

    Energy Technology Data Exchange (ETDEWEB)

    Franzius, C.; Schober, O. [Muenster Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Dietlein, M. [Koeln Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Biermann, M. [Haukeland University Hospital, Bergen (Norway). Nuclear Medicine and PET-Center; Bergen Univ. (Norway). Dept. of Surgical Sciences; Fruehwald, M.; Linden, T. [Universitaetsklinikum Muenster (Germany). Klinik und Poliklinik fuer Kinderheilkunde; Bucsky, P. [Luebeck Univ. (Germany). Haematologie, Onkologie und Immunologie der Klinik fuer Kinder- und Jugendmedizin; Reiners, C. [Wuerzburg Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin


    The procedure guideline for radioiodine ({sup 131}I) therapy and {sup 131}I whole-body scintigraphy of differentiated thyroid cancer in paediatric patients is the counterpart to the procedure guidelines (version 3) for adult patients and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. Characteristics of thyroid cancer in children are the higher aggressiveness of papillary thyroid cancer, the higher frequency of extrathyroidal extension and of disseminated pulmonary metastases as well as the high risk of local recurrences. Radioiodine therapy is generally recommended in children, the {sup 131}I activity depends on the children's body weight. Radioiodine ablation in children with small papillary cancer ({<=}1 cm) should be considered. TSH stimulation is reached two weeks (children) or three weeks (adolescents) after withdrawal of thyroid hormones. Anti-emetic drugs are highly recommended. CT of the chest and examination of pulmonary function are clearly indicated if there is any suspicion on metastases. 3-6 months after {sup 131}I ablation, the {sup 131}I whole-body scintigraphy is highly recommended as lymph node metastases are frequently detected in paediatric patients. Follow-up care should be arranged in shorter intervals than in adults to test the compliance and to adapt dosage of thyroid hormones to the children's body weight. Reference values of fT3 are higher in children than in adults. Evidence is insufficient to describe in which constellation the TSH may be kept within the low normal level. Therefore, TSH suppression is generally recommended. (orig.)

  12. Comparison of the Influence on the Liver Function Between Thyroid Hormone Withdrawal and rh-TSH Before High-Dose Radioiodine Therapy in Patients with Well-Differentiated Thyroid Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Han, Yeon-Hee; Lim, Seok Tae; Yun, Kuk-No; Yim, Sung Kyun; Kim, Dong Wook; Jeong, Hwan-Jeong; Sohn, Myung-Hee [Chonbuk National Univ. Medical School and Hospital, Jeonju (Korea, Republic of)


    An elevated thyroid stimulating hormone level (TSH) is essential to stimulate the uptake of radioiodine into thyroid remnants and metastases and metastases of thyroid cancer when a patient under-goes high-dose radioiodine therapy. Nowadays, recombinant human thyroid stimulating hormone (rh-TSH) is increasingly used instead of the classic method of thyroid hormone withdrawal (THW). However, beyond the therapeutic effects, clinical differences between the two methods have not yet been clearly demonstrated. The aim of this work was to investigate the effects of the two methods, especially on liver function. We identified 143 evaluable patients who were further divided into two groups: THW and rh-TSH. We first reviewed the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, which were measured during the admission period for total thyroidectomy. We called these liver enzyme levels 'base AST' and 'base ALT.' We also assessed other chemistry profiles, including AST, ALT, total cholesterol, LDL cholesterol, alkaline phosphatase (ALP), total bilirubin (TB), and triglyceride (TG), which were measured on admission day for high-dose radioiodine therapy. We called these liver enzyme levels 'follow-up AST'and 'follow-up ALT.' We compared the changes in base and follow-up liver enzyme levels and the other chemistry profiles between the two groups. The base AST and base ALT levels of the two groups were within normal range, and there was no significant difference between the two groups. In contrast to these base liver enzyme levels, follow-up AST and ALT levels than did the rh-TSH group. Patients in the THW group. Patients in the THW group also had higher levels of total cholesterol and LDL cholesterol than did the patients in the rh-TSH group. However there were no statistically significant differences in ALP, total bilirubin, and triglyceride levels between the two groups. In this retrospective analysis of liver

  13. Combination of ultrasound-guided percutaneous microwave ablation and radioiodine therapy in benign thyroid disease. A 3-month follow-up study

    Energy Technology Data Exchange (ETDEWEB)

    Korkusuz, H.; Happel, C.; Koch, D.A.; Gruenwald, F. [Frankfurt University Hospital (Germany). Dept. of Nuclear Medicine


    Pilot studies of combined therapies treating benign nodular goiters reported promising results. The aim of this study was to investigate the effectiveness of combined microwave ablation (MWA) and radioiodine therapy (RIT) with a special focus on thyroid function at the 3-month follow-up. 15 patients (median age: 55 years) with a large goiter and benign thyroid nodules or Graves' disease were treated with the combined therapy. Serum levels of triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), thyroglobuline (Tg) and, additionally, antibody levels against thyroglobulin (TgAb), thyrotropin receptors (TRAb) and thyroid peroxidase (TPOAb) were measured at enrollment, post MWA and at the 3-month follow-up (3MFU). Furthermore, the goiter volume, I-131 dose and hospitalization time were analyzed to evaluate effectiveness. MWA was operated under local anesthesia with a system working in a wavelength field of 902 to 928 MHz. TSH, T4, T3 and Tg did not change at 3MFU, except for in two patients in whom the initial TSH levels improved to normal thyroid functioning levels at follow-up. One of the patients developed a high TRAb-level that receded back into the normal range. At 3MFU, the combined therapy showed a mean thyroid volume reduction of 26.4 ml ± 7.9 ml (30.5 % ± 4.6 % (p < 0.05)). By utilizing the combined therapy, administered activity could be reduced by 26.6 % ± 4.8 % (p < 0.05) and hospitalization time by 30.9 % ± 19.9 % (p < 0.05). The data confirmed the effectiveness of the combination of MWA with RIT. The combined therapy is an innovative and conservative approach and could become a safe alternative to surgery for the treatment of very large benign nodular goiters. Due to the short follow-up and the limited number of patients, further studies will be necessary.

  14. Comparative analysis of the countermeasures taken to mitigate exposure of the public to radioiodine following the Chernobyl and Fukushima accidents: lessons from both accidents. (United States)

    Uyba, Vladimir; Samoylov, Alexander; Shinkarev, Sergey


    In the case of a severe radiation accident at a nuclear power station, the most important radiation hazard for the public is internal exposure of the thyroid to radioiodine. The purposes of this paper were (i) to compare countermeasures conducted (following the Chernobyl and Fukushima accidents) aimed at mitigation of exposure to the thyroid for the public, (ii) to present comparative estimates of doses to the thyroid and (iii) to derive lessons from the two accidents. The scale and time of countermeasures applied in the early phase of the accidents (sheltering, evacuation, and intake of stable iodine to block the thyroid) and at a later time (control of 131I concentration in foodstuffs) have been described. After the Chernobyl accident, the estimation of the thyroid doses for the public was mainly based on direct thyroid measurements of ~400 000 residents carried out within the first 2 months. The highest estimates of thyroid doses to children reached 50 Gy. After the Fukushima accident, the estimation of thyroid doses was based on radioecological models due to a lack of direct thyroid measurements (only slightly more than 1000 residents were measured). The highest estimates of thyroid doses to children were a few hundred mGy. Following the Chernobyl accident, ingestion of 131I through cows' milk was the dominant pathway. Following the Fukushima accident, it appears that inhalation of contaminated air was the dominant pathway. Some lessons learned following the Chernobyl and Fukushima accidents have been presented in this paper. © The Author(s) 2018. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  15. Autoradiographic localization of delta opioid receptors within the mesocorticolimbic dopamine system using radioiodinated (2-D-penicillamine, 5-D-penicillamine)enkephalin ( sup 125 I-DPDPE)

    Energy Technology Data Exchange (ETDEWEB)

    Dilts, R.P.; Kalivas, P.W. (Washington State Univ., Pullman (USA))


    The enkephalin analog (2-D-penicillamine, 5-D-penicillamine)enkephalin was radioiodinated (125I-DPDPE) and shown to retain a pharmacological selectivity characteristic of the delta opioid receptor in in vitro binding studies. The distributions of 125I-DPDPE binding, using in vitro autoradiographic techniques, were similar to those previously reported for the delta opioid receptor. The nucleus accumbens, striatum, and medial prefrontal cortex contain dense gradients of 125I-DPDPE binding in regions known to receive dopaminergic afferents emanating from the mesencephalic tegmentum. Selective chemical lesions of the ventral tegmental area and substantia nigra were employed to deduce the location of the 125I-DPDPE binding within particular regions of the mesocorticolimbic dopamine system. Unilateral lesions of dopamine perikarya (A9 and A10) within the ventral tegmental area and substantia nigra produced by mesencephalic injection of 6-hydroxydopamine resulted in significant (20-30%) increases in 125I-DPDPE binding contralateral to the lesion within the striatum and nucleus accumbens. Lesions of the perikarya (dopaminergic and nondopaminergic) of the ventral tegmental area, induced by quinolinic acid injections, caused increases of less magnitude within these same nuclei. No significant alterations in 125I-DPDPE binding were observed within the mesencephalon as a result of either treatment. The specificity of the lesions was confirmed by immunocytochemistry for tyrosine hydroxylase. These results suggest that the enkephalins and opioid agonists acting through delta opioid receptors do not directly modulate dopaminergic afferents but do regulate postsynaptic targets of the mesocorticolimbic dopamine system.

  16. Expression Patterns of Glucose Transporter-1 Gene and Thyroid Specific Genes in Human Papillary Thyroid Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sungeun; Chung, Junekey; Min Haesook and others


    The expression of glucose transporter-1 (Glut-1) gene and those of major thyroid-specific genes were examined in papillary carcinoma tissues, and the expressions of these genes were compared with cancer differentiation grades. Twenty-four human papillary carcinoma tissues were included in this study. The expressions of Glut-1- and thyroid-specific genes [sodium/iodide symporter (NIS), thyroid peroxidase, thyroglobulin, TSH receptor and pendrin] were analyzed by RT-PCR. Expression levels were expressed as ratios versus the expression of beta-actin. Pathologic differentiation of papillary carcinoma was classified into a relatively well-differentiated group (n=13) and relatively less differentiated group (n=11). Glut-1 gene expression was significantly higher in the less differentiated group (0.66±0.04) than in the well-differentiated group (0.59±0.07). The expression levels of the NIS, PD and TG genes were significantly higher in the well-differentiated group (NIS: 0.67±0.20, PD: 0.65±0.21, TG: 0.74±0.16) than in the less differentiated group (NIS: 0.36±0.05, PD: 0.49±0.08, TG: 0.60±0.11), respectively. A significant negative correlation was found between Glut-1 and NIS expression, and positive correlations were found between NIS and TG, and between NIS and PD. The NIS, PD and TG genes were highly expressed in well-differentiated thyroid carcinomas, whereas the Glut-1 gene was highly expressed in less differentiated thyroid carcinomas. These findings provide a molecular rationale for the management of papillary carcinoma, especially in the selection of FDG PET or radioiodine whole-body scan and I-131-based therapy.

  17. Radioiodine therapy for combined disseminated and nodular thyroid autonomy. Results after using a correction term for the disseminated part; Radioiodtherapie bei kombinierter Schilddruesenautonomie. Ergebnisse nach Korrektur fuer disseminierte Anteile

    Energy Technology Data Exchange (ETDEWEB)

    Vogt, H.; Dorn, R.; Otto, I.; Sciuk, J. [Klinik fuer Nuklearmedizin, Klinikum Augsburg (Germany); Wengenmair, H.; Kopp, J. [Medizinische Physik und Strahlenschutz, Klinikum Augsburg (Germany)


    Aim: in combined focal and disseminated thyroid autonomy a variety of concepts in the treatment with radioiodine are used. The difference lies mainly in the calculation of the autonomous volume. This retrospective study shows a new method of calculating the autonomous volume. Patients and methods: in 398 patients with combined thyroid autonomy and good correlation of scintigraphically hot nodules and lesions defined by ultrasound the volume of the nodules is ascertained from scintigraphic and ultrasound parameters and the volume of the disseminated autonomous tissue is assessed with a weighting factor (VF). This factor is the ratio of impulse density in a ROI over the disseminated volume divided by the corresponding impulse density over the nodular volume of the thyroid scintigraphy. The sum of nodular volume and weighted perinodular volume gives the total autonomous volume. A standard radioiodine test gives the maximum iodine-131-uptake and effective half-life to calculate the activity to obtain a treatment dose of 400 Gy. Results: the rate of success with and without thyrostatic medication was 97% with an 18.6% rate of hypothyroidism observed from 4 months post therapy onwards. Conclusion: the use of the weighting factor VF in the treatment of combined autonomy leads to an excellent rate of success in patients with good correlation of functional imaging and ultrasound findings. (orig.)

  18. Evaluation of radioiodine therapy with fixed doses of 10 and 15 mCi in patients with Graves disease; Avaliacao da radioiodoterapia com doses fixas de 10 e 15 mCi em pacientes com doenca de Graves

    Energy Technology Data Exchange (ETDEWEB)

    Canadas, Viviane; Vilar, Lucio; Moura, Eliane; Brito, Ana; Castellar, Enio [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Hospital das Clinicas. Servico de Endocrinologia]. E-mail:


    The treatment options for the hyperthyroidism of Graves' disease are antithyroid drugs, surgery and radioiodine, none of which is considered ideal, as they do not act directly on the etiopathogenesis of the disease. Radioiodine has been increasingly used as the treatment of choice because it is a safe and definitive therapy whose administration is very easy. Some authors prefer to administer higher doses in order to deliberately induce hypothyroidism, while others recommend lower doses that result in a lower incidence of hypothyroidism and a greater incidence of euthyroidism. There is no consensus for the optimal regimen of fixed doses to be used and this is the main focus of the present study, where doses of 10 and 15 mCi of {sup 131}I were compared. Among the 164 patients analyzed, 61 (37.2%) were submitted to 10 mCi and 103 (62.8%) to 15 mCi. In the longitudinal analysis it was observed that remission of the hyperthyroidism was statistically different in the sixth month (p < 0.001), being higher in the group that used the dose of 15 mCi, but similar in both groups at 12 and 24 months. It may be concluded that the administration of fixed doses of 10 and 15 mCi of {sup 131}I brought about a similar remission of the hyperthyroidism after 12 months of treatment. Moreover, the remission rate of the hyperthyroidism had no association with age, sex or previous therapy with antithyroid drugs. (author)

  19. Myeloid Sarcoma of the Uterine Cervix as Presentation of Acute Myeloid Leukaemia after Treatment with Low-Dose Radioiodine for Thyroid Cancer: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Anne Sophie Weingertner


    Full Text Available The development of acute myeloid leukaemia after low-dose radioiodine therapy and its presentation as a myeloid sarcoma of the uterine cervix are both rare events. We report a case of acute myeloid leukaemia revealed by a myeloid sarcoma of the uterine cervix in a 48-year-old woman, 17 months after receiving a total dose of 100 mCi 131I for papillary thyroid cancer. A strict hematological follow-up of patients treated with any dose of 131I is recommended to accurately detect any hematological complications which might have been underestimated. Unusual presentations, such as chloroma of the uterine cervix, may reveal myeloid malignancy and should be kept in mind.

  20. HiLo: Multicentre randomized phase III clinical trial of high vs low dose radioiodine, with or without recombinant human thyroid stimulating hormone (rhTSH), for remnant ablation for differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mallick, U. [Freeman Hospital, Newcastle, Newcastle upon Tyne (United Kingdom); Harmer, C.; Clarke, S.; Moss, L.; Nicol, A.; Clarke, P.; Smellie, J.; McCready, R.; Farnell, K.; Franklyn, J.; John, R.; Nutting, C.; Yap, B.; Lemon, C.; Wadlsey, J.; Gerrard, G.; Roques, T.; Macias, E.; Whitaker, S.; Abdul-Hamid, A.; Alvarez, P.; Kadalayil, L.; Hackshaw, A.


    Recommended treatment for most patients with differentiated thyroid cancer is surgery followed by radioiodine ablation. Current practice in many centres is to use a high administered activity of 3.7 GBq (100 mCi). However, a lower activity (1.1 GBq or 30 mCi) has advantages including a shorter stay in hospital isolation and lower risk of side effects, including the risk of a second cancer. Also, Thyrogen (rhTSH) allows patients to continue thyroid hormone replacement during ablation, avoiding symptoms of hypothyroidism and also reduces total body radiation dose. We conducted a large randomized factorial multi centre trial to simultaneously address whether ablation success rates are similar using (i) either 1.1 GBq or 3.7 GBq, and (ii) either Thyrogen or thyroid hormone withdrawal. It is the first ever national prospective trial in thyroid cancer in the UK. Final results will be available in 2011

  1. Use of recombinant, human TSH radioiodine therapy in patients with differentiated thyroid carcinoma; Radioiodtherapie des differenzierten Schilddruesenkarzinoms nach Vorbehandlung mit rekombinantem, humanem TSH

    Energy Technology Data Exchange (ETDEWEB)

    Luster, M. [Wuerzburg Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin


    We describe the use of recombinant human TSH (rhTSH) in conjunction with ablative radioiodine therapy (RIT) in 11 patients (16 total treatments) with advanced and/or recurrent DTC (5 papillary, 6 follicular) for whom withdrawal of thyroid hormone suppressive therapy (THST) to increase serum TSH was not an option. Indications for rhTSH use in these patients included inability to tolerate withdrawal of thyroid hormones due to poor physical condition or inability to achieve sufficient serum TSH levels after THST withdrawal. All patients had undergone thyroidectomy and most (9/11) had received prior radioablative therapy after THST withdrawal. In 7 cases (5 patients), post-therapy Tg levels assessed at a mean of 4.3 months (range 2-10 months) after I-131 therapy were decreased by at least 30% compared to pre-therapy levels. In an additional 3 patients, whole body scans performed at follow-up indicated decreased or stabilized tumor burden compared to pre-therapy scans or marked clinical improvement was found. Three patients died of progressive disease within 2 months of therapy before follow-up assessments occurred. No adverse events were reported among the 8 surviving patients. The results suggest that rhTSH offers a promising alternative to THST withdrawal to allow radioablative therapy under maximal TSH stimulation in patients with advanced recurrent DTC who would not otherwise be able to receive this treatment. This therapeutic indication extends the clinical potential of the new agent, already demonstrated to be effective for use with I-131 for diagnostic purposes. However in some patients suffering from highly aggressive tumors the poor prognosis will not be improved. (orig.) [German] An unserer Klinik liegen bislang Erfahrungen mit 16 Radioiodtherapien (RIT) (z.T. mehrfache Anwendung) unter rhTSH vor. Die ueberwiegende Mehrzahl der Patienten wurde wegen einer fortgeschrittenen Tumorerkrankung mit dem Risiko einer lebensbedrohlichen Verschlechterung in

  2. Comparison of therapeutic efficacy and clinical parameters between recombinant human thyroid stimulating hormone and thyroid hormone withdrawal in high-dose radioiodine treatment with differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Se Hun; Na, Chang Ju; Kim, Jeong Hun; Han, Yeon Hee; KIm, Hee Kwon; Jeong, Hwan Jeong; Sohn, Myung Hee; Lim, Seok Tae [Dept. of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)


    High-dose radioiodine treatment (HD-RIT) after injection of recombinant human thyroid stimulating hormone (rh-TSH) has become widely used. This study compared the therapeutic efficacy of HD-RIT and clinical parameters between rh-TSH supplement and thyroid hormone withdrawal (THW) after total thyroidectomy in patients with differentiated thyroid cancer. We retrospectively reviewed 266 patients (47 male and 219 female; age, 49.0 ± 10.9 years) with differentiated thyroid cancer detected from September 2011 to September 2012. Patients comprised THW (217, 81.6 %) and rh-TSH (49, 18.4 %). Inclusion criteria were: first HD-RIT; any TN stage; absence of distant metastasis. To evaluate the complete ablation of the remnant thyroid tissue or metastasis, we reviewed stimulated serum thyroglobulin (sTg), I-123 whole-body scan (RxWBS) on T4 off-state, and thyroid ultrasonography (US) or [F-18]-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) 6–8 months after HD-RIT. We defined a complete ablation state when all three of the follow-up conditions were satisfied; <2.0 ng/ml of the sTg, I-123 RxWBS (−), and thyroid US or F-18 FDG PET/CT (−). If one of the three was positive, ablation was considered incomplete. We also compared various clinical biomarkers (body weight, body mass index, liver and kidney function) between THW and rh-TSH groups. The rates of complete ablation were 73.7 % (160/217) for the THW group and 73.5 % (36/49) for the rh-TSH group. There was no significant difference between the two groups (p = 0.970). The follow-up aspartate transaminase (p = 0.001) and alanine transaminase (p = 0.001) were significantly higher in the THW group. The renal function parameters of blood urea nitrogen (p = 0.001) and creatinine (p = 0.005) tended to increase in the THW group. The change of body weight was + Δ0.96 (±1.9) kg for the THW group and was decreased by -Δ1.39 (±1.5) kg for the rh-TSH group. The change

  3. The Evaluation of Thyroid Disease in the U.S.A. Resulting from Combined Exposures to Radioiodine Fallout: a case study

    Energy Technology Data Exchange (ETDEWEB)

    Baverstock, K. [WHO Regional Office for Europe, Helsinki (Finland); Hoffman, F.O. [SENES Oak Ridge, Inc., Oak Ridge, TN (United States); Pritikin, T. [Berkeley, CA (United States)


    At the time of weapons testing in Nevada and associated activities elsewhere in mainland USA, the risks to health associated with fission product fallout were not appreciated in the way they are today. In retrospect, however, there is evidence to suggest a reluctance of the scientific community to accept the evolving evidence of harm from {sup 131}I, from the 1980s onwards. Some of this reluctance is based on extensive epidemiological follow-up of patients irradiated with diagnostic medical applications of {sup 131}I, which showed a very small effect. The epidemiological community concerned with the {sup 131}I diagnostic studies have proved to be among the most resistant to the abandonment of the belief in the reduced carcinogenic effectiveness of {sup 131}I. However, as early as 1982 Congress mandated the Department of Health and Human Services to review the doses from {sup 131}I to the public as a result of public concern for a rising incidence of thyroid disease. The Lee et al experiment was published in 1982. The conflict between the results of the Lee et al experiments and the earlier studies of the relative carcinogenicity of external radiation and {sup 131}I, led the National Cancer Inst. to take the unusual step, in the mid 1980s, of arranging an independent evaluation of the work on which the Lee paper was based. The review, the results of which were not published, endorsed the results given in the paper. Finally, the evidence of an increase in thyroid cancer after the Chernobyl accident was published in 1992. What were the factors that contributed to this resistance by the scientific community to abandoning an increasingly untenable belief? One factor could have been the use, in the US, of {sup 131}I for medical diagnostic purposes in children and reluctance to accept that this might have been damaging to health in later life. Another possibility was the recognition that, in the event of an accident to a nuclear power plant, release of radio-iodine

  4. Radiochemotherapy of hepatocarcinoma via lentivirus-mediated transfer of human sodium iodide symporter gene and herpes simplex virus thymidine kinase gene

    Energy Technology Data Exchange (ETDEWEB)

    Chen Libo, E-mail: [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China); Guo Guoying [Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018 (China); Liu Tianjing; Guo Lihe [Division of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Zhu Ruisen [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China)


    Herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system has been widely used as a traditional gene therapy modality, and the sodium/iodide symporter gene (NIS) has been found to be a novel therapeutic gene. Since the therapeutic effects of radioiodine therapy or prodrug chemotherapy on cancers following NIS or HSV-TK gene transfer need to be enhanced, this study was designed to investigate the feasibility of radiochemotherapy for hepatocarcinoma via coexpression of NIS gene and HSV-TK gene. Methods: HepG2 cells were stably transfected with NIS, TK and GFP gene via recombinant lentiviral vector and named HepG2/NTG. Gene expression was examined by reverse transcriptase polymerase chain reaction, fluorescence imaging and iodide uptake. The therapeutic effects were assessed by MTT assay and clonogenic assay. Results: HepG2/NTG cells concentrated {sup 125}I{sup -} up to 76-fold higher than the wild-type cells within 20 min, and the efflux happened with a T{sub 1/2eff} of less than 10 min. The iodide uptake in HepG2/NTG cells was specifically inhibited by sodium perchlorate. Dose-dependent toxicity to HepG2/NTG cells by either GCV or {sup 131}I was revealed by clonogenic assay and MTT assay, respectively. The survival rate of HepG2/NTG cells decreased to 49.7%{+-}2.5%, 43.4%{+-}2.8% and 8.6%{+-}1.2% after exposure to {sup 131}I, GCV and combined therapy, respectively. Conclusion: We demonstrate that radiochemotherapy of hepatocarcinoma via lentiviral-mediated coexpression of NIS gene and HSV-TK gene leads to stronger killing effect than single treatment, and in vivo studies are needed to verify these findings.

  5. Prognostic impact of incomplete surgical clearance of radioiodine sensitive local lymph node metastases diagnosed by post-operative {sup 124}I-NaI-PET/CT in patients with papillary thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Binse, Ina; Grafe, Hong; Goerges, Rainer; Poeppel, Thorsten D.; Bockisch, Andreas; Rosenbaum-Krumme, Sandra J. [University Duisburg-Essen, Department of Nuclear Medicine, Essen (Germany); Ezziddin, Samer [Saarland University, Department of Nuclear Medicine, Homburg (Germany)


    Nodal involvement is an independent risk factor of recurrence in papillary thyroid cancer (PTC). Neither the international guidelines nor the recently introduced ongoing risk adaptation concept consider the extent of initial surgical clearance of radioiodine sensitive lymph node metastases in their stratification systems. We investigated the prognostic relevance of incomplete initial surgical clearance in patients with purely lymphogeneous metastatic PTC (pN1 M0) despite successful radioiodine therapy. Accurate assessment of pre-ablative nodal status was attempted using PET/CT studies with both {sup 124}I-NaI and {sup 18}F-FDG along with high-resolution cervical ultrasound. Sixty-five patients with histologically diagnosed lymph node metastases (pN1 M0) were retrospectively analyzed. Patients with iodine-negative lymph node metastases diagnosed by {sup 18}F-FDG PET/CT or distant metastases were excluded from the analysis. The association of disease recurrence with the pre-ablative nodal status, as well as other baseline characteristics, were examined applying nonparametric tests for independent samples and multiple regression analysis. Patients with persistent lymph node metastases in {sup 124}I-NaI PET/CT were further divided according to the additional presence or absence of FDG-uptake in {sup 18}F-FDG PET/CT. Survival analyses were performed using Kaplan-Meier curves and the Cox proportional hazards model for uni- and multivariate analyses to assess the influence of prognostic factors on progression free survival (PFS). Incomplete metastatic lymph node resection captured by {sup 124}I-NaI PET/CT (n = 33) was an independent risk factor for recurrence (61 % vs 25 %, p = 0.006) and shorter PFS (46 months vs not reached, HR 4.0 [95 %-CI, 1.7-9.2], p = 0.001). Ultrasound could detect lymph node metastases only in 19/33 patients (58 %). Among patients with positive nodal status, FDG-avidity of metastatic iodine positive lymph nodes worsened the outcome (16 vs 69

  6. Usefulness of recombinant human TSH-aided radioiodine doses administered in patients with differentiated thyroid carcinoma Administración de dosis terapéuticas de radioyodo luego de TSH recombinante en pacientes con carcinoma diferenciado de tiroides

    Directory of Open Access Journals (Sweden)

    Fabián Pitoia


    Full Text Available The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have led to an increased interest in its use for preparation for radioiodine (RI dose administration in patients with recurrent or persistent differentiated thyroid carcinoma (DTC. In order to establish the efficacy of RI therapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients. Patients were divided into two groups: GI (n=17, with previous thyroid bed uptake and undetectable thyroglobulin (Tg levels under levothyroxine treatment and GII (n=11, with proven metastatic local or distant disease. Median follow-up after the first rhTSH-aided radioiodine treatment was 32 ± 13 months (range 8 to 54 months. Sixteen patients (94% in GI were rendered disease free and one patient was shown to have persistent disease. In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, in four in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels were undetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free, four patients died (three due to thyroid cancer and five out of the remaining patients have persistent disease. In conclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94% patients (GI. rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSH is a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing the quality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patients only with stimulated Tg levels.Los estudios publicados que confirman la seguridad y eficacia de la TSH recombinante (rhTSH llevaron a un incremento en el interés para su uso como adyuvante terapéutico en el CDT (ablación o tratamiento

  7. Gene Therapy (United States)

    Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

  8. Evaluation of Lentiviral-Mediated Expression of Sodium Iodide Symporter in Anaplastic Thyroid Cancer and the Efficacy of In Vivo Imaging and Therapy

    Directory of Open Access Journals (Sweden)

    Chien-Chih Ke


    Full Text Available Anaplastic thyroid carcinoma (ATC is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to 131I therapy due to loss of sodium iodide symporter (NIS gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of 131I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy.

  9. An Evaluation of Deviation from the International Atomic Energy Agency-International Commission on Radiological Protection Proposed Equation for Calculation of Radiation Dose Rate Emanating from the Patients with Differentiated Thyroid Cancer Undergoing Radioiodine (I-131) Therapy. (United States)

    Dehkordi, Forough Jafarian; Rasuli, Behrouz; Mahmoud-Pashazadeh, Ali


    The main purpose of this study was to investigate dose rate emanating from patients treated with (131)I to evaluate which of the theoretical formulas, inverse-square law (ISL) and International Atomic Energy Agency-International Commission on Radiological Protection (IAEA-ICRP) suggested equation, can provide a sufficiently close approximation of the measured dose rate. Measurements were performed based on the IAEA safety report No. 63 method at 0, 12, 24, and 48 h after administration of radioiodine at a distance of 1 m for 69 patients and for the rest of 67 patients, dose rate was measured at 2, 4, 24, and 48 h at a distance of 2 m. Results revealed that the ISL formula gained better approximation of measured dose rates than the IAEA-ICRP equation with the lesser error. The ISL formula is still more reliable than the novel method of dose calculation in the vicinity of patients. This finding reminded us the prime importance of distance as a radiation protection principle.

  10. Stereoselective synthesis, in vitro, and initial in vivo evaluation of 1-methylpiperidin-4-yl {alpha}-hydroxy-{alpha}-(1-iodo-1-propen-3-yl)-{alpha}-phenylacetate (IPIP): a novel radioiodinated molecular probe with high affinity for the muscarinic receptor

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, Daniel W. E-mail: mcphersod@CSR.NIH.GOV; Breeden, William K.; Beets, Arnold L.; Luo, Huimin; Sood, Victor; Knapp, Furn F


    1-Methylpiperidin-4-yl {alpha}-hydroxy-{alpha}-(1-iodo-1-propen-3-yl)-{alpha}-phenylacetate (IPIP) was investigated as a potential radioiodinated molecular probe targeted to the muscarinic receptor complex. The IPIP stereoisomers were synthesized via a chiral intermediate in >95% enantiomeric excess. The R-isomers demonstrated a M{sub 1} to M{sub 2} subtype selectivity of approximately 3 to 1 and the S-isomers demonstrated non-subtype selective binding in vitro. IPIP was radiolabeled with iodide-125 with an average radiochemical yield of 74.4% ({+-}14.8, n 5), specific activities >800 mCi/{mu}mol, and radiochemical purities >97%. In vivo the Z-isomers demonstrated high uniform cerebral uptake suggesting non-subtype selective binding. In contrast, E-R-IPIP, after allowing a low uptake in M{sub 2} rich areas to clear, demonstrated a retention of activity in M{sub 1} and M{sub 4} rich cerebral regions. In addition, the cerebral uptake of E-R-IPIP and Z-S-IPIP were inhibited by 70-90% via pretreatment with R-QNB, an established muscarinic antagonist. An ex vivo metabolism study demonstrated Z-S-IPIP was stable at the receptor site with an absence of radiolabeled metabolites.

  11. gene structure, gene expression

    Indian Academy of Sciences (India)

    Primer 5.0 software. To adjust for RNA quality and diffe- rences in cDNA concentration, we amplified actin as an internal control with the following primers: PtActin-F (5′-TG. AAGGAGAAACTTGCGTAT-3′) and PtActin-R (5′-GCA. CAATGTTACCGTACAGAT-3′). These genes were ampli- fied from first-strand cDNA using ...

  12. Contribution of radio-iodine 131 in the treatment of Grave's Basedow disease in the department of nuclear medicine of Ibn Sina Hospital in Rabat; Apport de l'iode 131 dans le traitement de la maladie de Basedow dans le service de medecine nucleaire de l'hopital Ibn Sina de Rabat

    Energy Technology Data Exchange (ETDEWEB)

    Mbodj, M.; Amjad, I. [Faculte de Medecine de Dakar, Lab. de Biophysique et de Medecine Nucleaire, UCAD, Dakar (Senegal); Guerrouj, H.; Ben Rais, N.A. [Hopital Ibn Sina de Rabat, Service de Medecine Nucleaire, Rabat (Morocco)


    One hundred and twenty-nine Grave's Basedow diseases in any gender and variable age patients, coming from several cities of Morocco, were randomized in a study of radio-iodine treatment who took place at the nuclear medicine department of Ibn Sina Hospital (Rabat, Morocco) during the period (from January 2001 to December 2008). The radio-iodine treatment was a first, second or third option and radio-iodine activities delivered varied (from 222 to 555 MBq 6 to 15 mCi) according to the age, the thyroid volume, the degree of hyperthyroidism and socio-economical situation. The high amounts of {sup 131}I were reserved especially to the patients who live far and whose socio-economic level is low with an aim of quickly obtaining an easily controllable state of hypothyroidism by a substitute treatment. The results showed that: (1) 57.36% of patients reverted to euthyroidism (n = 74) with a patient having received two {sup 131}I cures. The second cure was justified by recurrence of hyperthyroidism after the first cure; (2) 34.88% passed in hypothyroidism (n = 45) with three patients having received two cures of {sup 131}I, the second cure was justified by recurrence of hyperthyroidism after the first cure in two patients and by the persistence of the hyperthyroidism after the first cure for the third patient. The average time of passage in hypothyroidism was 4.5 months; (3) 7.76% had remained in hyperthyroidism after the radioactive iodine treatment. Finally, 92.24% of our patients treated by radioactive iodine had passed in euthyroidism or hypothyroidism against 7.76% whose hyperthyroidism had persisted or occurred. (authors)

  13. Gene Locater

    DEFF Research Database (Denmark)

    Anwar, Muhammad Zohaib; Sehar, Anoosha; Rehman, Inayat-Ur


    UNLABELLED: Locating genes on a chromosome is important for understanding the gene function and its linkage and recombination. Knowledge of gene positions on chromosomes is necessary for annotation. The study is essential for disease genetics and genomics, among other aspects. Currently available...... software's for calculating recombination frequency is mostly limited to the range and flexibility of this type of analysis. GENE LOCATER is a fully customizable program for calculating recombination frequency, written in JAVA. Through an easy-to-use interface, GENE LOCATOR allows users a high degree...

  14. Thyroid-Specific Genes Expression Uncovered Age-Related Differences in Pediatric Thyroid Carcinomas

    Directory of Open Access Journals (Sweden)

    Maria Isabel Cunha Vieira Cordioli


    Full Text Available Despite a more advanced stage of disease at presentation, a better response to radioiodine (RAI therapy and a reduced overall mortality have been reported in pediatric differentiated thyroid cancer (DTC in comparison to adult DTC. Few studies suggested that the better response to RAI therapy in pediatric patients might be associated with an increased expression of NIS. However, a marked heterogeneity within the pediatric group has been recognized. Children (<10 years old usually present a more aggressive disease than adolescents (≥10–18 years old. By analyzing the expression of thyroid-specific genes in 38 sporadic pediatric tumors, we show that the expression of NIS, PDS, and TSHR was lower in children than adolescents (P<0.05. A linear regression confirmed the association between NIS expression and age. Most significantly, NIS was expressed at similar levels in DTC from children and adults, whereas PDS and TSHR expression was even lower in DTC from children, compared to adolescents and adults. Our data suggest that biological behaviors of DTC in adolescents might differ from those in children and adults. Therefore, the premise that the expression of thyroid-specific genes is higher in tumors from pediatric patients than in adults is not entirely true and might be too oversimplified.

  15. Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus

    Directory of Open Access Journals (Sweden)

    Mittra Arjun


    Full Text Available Abstract Introduction Oncolytic viruses show promise for treating cancer. However, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. This study aimed to determine if insertion of the human sodium iodide symporter (hNIS cDNA as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153. Methods GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry hNIS via homologous recombination. GLV-1h153 was tested against human pancreatic cancer cell line PANC-1 for replication via viral plaque assays and flow cytometry. Expression and transportation of hNIS in infected cells was evaluated using Westernblot and immunofluorescence. Intracellular uptake of radioiodide was assessed using radiouptake assays. Viral cytotoxicity and tumor regression of treated PANC-1tumor xenografts in nude mice was also determined. Finally, tumor radiouptake in xenografts was assessed via positron emission tomography (PET utilizing carrier-free 124I radiotracer. Results GLV-1h153 infected, replicated within, and killed PANC-1 cells as efficiently as GLV-1h68. GLV-1h153 provided dose-dependent levels of hNIS expression in infected cells. Immunofluorescence detected transport of the protein to the cell membrane prior to cell lysis, enhancing hNIS-specific radiouptake (P In vivo, GLV-1h153 was as safe and effective as GLV-1h68 in regressing pancreatic cancer xenografts (P 124I-PET. Conclusion Insertion of the hNIS gene does not hinder replication or oncolytic capability of GLV-1h153, rendering this novel virus a promising new candidate for the noninvasive imaging and tracking of oncolytic viral therapy.

  16. Establishment of a hepatocellular carcinoma cell line expressing dual reporter genes: sodium iodide symporter (NIS) and enhanced green fluorescence protein (EGFP)

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Won Jung; Koo, Bon Chul; Kwon, Mo Sun [Kyungpook National University School of Medicine, Daegu (Korea, Republic of)] (and others)


    Dual reporter gene imaging has several advantages for more sophisticated molecular imaging studies such as gene therapy monitoring. Herein, we have constructed hepatoma cell line expressing dual reporter genes of sodium iodide symporter (NIS) and enhanced green fluorescence protein (EGFP), and the functionalities of the genes were evaluated in vivo by nuclear and optical imaging. A pRetro-PN vector was constructed after separating NIS gene from pcDNA-NIS. RSV-EGFP-WPRE fragment separated from pLNRGW was cloned into pRetro-PN vector. The final vector expressing dual reporter genes was named pRetro-PNRGW. A human hepatoma (HepG2) cells were transfected by the retrovirus containing NIS and EGFP gene (HepG2-NE). Expression of NIS gene was confirmed by RT-PCR, radioiodine uptake and efflux studies. Expression of EGFP was confirmed by RT-PCR and fluorescence microscope. The HepG2 and HepG2-NE cells were implanted in shoulder and hindlimb of nude mice, then fluorescence image, gamma camera image and I-124 microPET image were undertaken. The HepG2-NE cell was successfully constructed. RT-PCR showed NIS and EGFP mRNA expression. About 50% of cells showed fluorescence. The iodine uptake of NIS-expressed cells was about 9 times higher than control. In efflux study, T{sub 1/2} of HepG2-NE cells was 9 min. HepG2-NE xenograft showed high signal-to-background fluorescent spots and higher iodine-uptake compared to those of HepG2 xenograft. A hepatoma cell line expressing NIS and EGFP dual reporter genes was successfully constructed and could be used as a potential either by therapeutic gene or imaging reporter gene.

  17. Trichoderma genes (United States)

    Foreman, Pamela [Los Altos, CA; Goedegebuur, Frits [Vlaardingen, NL; Van Solingen, Pieter [Naaldwijk, NL; Ward, Michael [San Francisco, CA


    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  18. Evaluation of the therapeutic efficacy of a VEGFR2-blocking antibody using sodium-iodide symporter molecular imaging in a tumor xenograft model

    Energy Technology Data Exchange (ETDEWEB)

    Cheong, Su-Jin; Lee, Chang-Moon; Kim, Eun-Mi [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Uhm, Tai-Boong [Faculty of Biological Science, Chonbuk National University, Jeonju-si, jeonbuk 561-756 (Korea, Republic of); Jeong, Hwan-Jeong, E-mail: [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Kim, Dong Wook; Lim, Seok Tae; Sohn, Myung-Hee [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of)


    Purpose: Vascular endothelial growth factor receptor 2-blocking antibody (DC101) has inhibitory effects on tumor growth and angiogenesis in vivo. The human sodium/iodide symporter (hNIS) gene has been shown to be a useful molecular imaging reporter gene. Here, we investigated the evaluation of therapeutic efficacy by molecular imaging in reporter gene transfected tumor xenografts using a gamma imaging system. Methods: The hNIS gene was transfected into MDA-MB-231 cells using Lipofectamine. The correlation between the number of MDA-MB-231-hNIS cells and the uptake of {sup 99m}Tc-pertechnetate or {sup 125}I was investigated in vitro by gamma imaging and counting. MDA-MB-231-hNIS cells were injected subcutaneously into mice. When the tumor volume reached 180-200 mm{sup 3}, we randomly assigned five animals to each of three groups representing different tumor therapies; no DC101 (control), 100 {mu}g, or 150 {mu}g DC101/mouse. One week and 2 weeks after the first injection of DC101, gamma imaging was performed. Mice were sacrificed 2 weeks after the first injection of DC101. The tumor tissues were used for reverse transcriptase-polymerase chain reaction (RT-PCR) and CD31 staining. Results: Uptake of {sup 125}I and {sup 99m}Tc-pertechnetate into MDA-MB-231-hNIS cells in vitro showed correlation with the number of cells. In DC101 treatment groups, the mean tumor volume was smaller than that of the control mice. Furthermore, tumor uptake of {sup 125}I was lower than in the controls. The CD31 staining and RT-PCR assay results showed that vessel formation and expression of the hNIS gene were significantly reduced in the tumor tissues of treatment groups. Conclusion: This study demonstrated the power of molecular imaging using a gamma imaging system for evaluating the therapeutic efficacy of an antitumor treatment. Molecular imaging systems may be useful in evaluation and development of effective diagnostic and/or therapeutic antibodies for specific target molecules.

  19. Gene Therapy (United States)

    ... or improve your body's ability to fight disease. Gene therapy holds promise for treating a wide range of diseases, such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS. Researchers are still studying how and ...

  20. Long-term efficacy of modified-release recombinant human thyrotropin augmented radioiodine therapy for benign multinodular goiter: results from a multicenter, international, randomized, placebo-controlled, dose-selection study. (United States)

    Fast, Søren; Hegedüs, Laszlo; Pacini, Furio; Pinchera, Aldo; Leung, Angela M; Vaisman, Mario; Reiners, Christoph; Wemeau, Jean-Louis; Huysmans, Dyde A; Harper, William; Rachinsky, Irina; de Souza, Hevelyn Noemberg; Castagna, Maria G; Antonangeli, Lucia; Braverman, Lewis E; Corbo, Rossana; Düren, Christian; Proust-Lemoine, Emmanuelle; Marriott, Christopher; Driedger, Albert; Grupe, Peter; Watt, Torquil; Magner, James; Purvis, Annie; Graf, Hans


    Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine ((131)I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with (131)I therapy. In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2 ± 9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0 mL; range 31.9-242.2 mL) were randomized to receive placebo (n=32), 0.01 mg MRrhTSH (n=30), or 0.03 mg MRrhTSH (n=33) 24 hours before a calculated (131)I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by computed tomography scan) at baseline, six months, and 36 months. Thyroid function and quality of life (QoL) was evaluated at three-month and yearly intervals respectively. At six months, TV reduction was enhanced in the 0.03 mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01 mg MRrhTSH group. At 36 months, the mean percent TV reduction from baseline was 44 ± 12.7% (SD) in the placebo group, 41 ± 21.0% in the 0.01 mg MRrhTSH group, and 53 ± 18.6% in the 0.03 mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03 mg MRrhTSH group, the subset of patients with basal (131)I uptake TV reduction at 36 months than the corresponding subset of patients in the placebo group (p=0.01). At 36 months, the largest relative increase in SCAT was observed in the 0.03 mg MRrhTSH group (13.4 ± 23.2%), but this was not statistically different from the increases observed in the placebo or the 0.01 mg MRrhTSH group (p=0.15). Goiter-related symptoms were reduced and QoL improved, without any enhanced benefit from using MRrhTSH. At three years, the prevalence of permanent hypothyroidism was 13%, 33%, and 45% in the placebo, 0.01 mg, and 0.03 mg MRrhTSH groups respectively. The overall safety profile of

  1. Assessments of whole body scan images (PCI) obtained in patients undergoing treatment of radioiodine (pre and post-treatment); Avaliacoes das imagens de pesquisa de corpo inteiro (PCI) obtidas em pacientes submetidos ao tratamento de radioiodoterapia (pre e pos-tratamento)

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Fernanda Karolina Mendonca da; Lopes Filho, Ferdinand de Jesus; Vieira, Jose Wilson; Souza, Milena Thays Barbosa de, E-mail:, E-mail:, E-mail:, E-mail: [Instituto Federal de Educacao, Ciencia e Tecnologia de Pernambuco (IFPE), Recife, PE (Brazil)


    Nuclear medicine is a medical specialty used for diagnosis and therapy of some diseases. For the treatment of differentiated thyroid carcinoma (papillary and follicular) Radioiodine therapy is employed, in order to eliminate the rest of thyroid tissue after removal of the thyroid (thyroidectomy). In radioiodine therapy is used radioisotope iodine-131 ({sup 131}I) as Sodium Iodide (NaI). The amount of the activity (dose) of {sup 131}I administered is generally the responsibility of nuclear medicine, which is based on an image Research Length of the patient (pre-dose therapy PCI). PCI is also used after treatment (post-PCI therapeutic dose) to evaluate possible metastasis. The purpose of this study was to investigate the distribution of biokinetic {sup 131}I at length and in some organs of the patient, in order to note any similarity. Exams PCI pre-dose and post-dose were analyzed, the anterior and posterior projections of ten patients. Contours in these images (ROI - Region Of Interest) were made in the whole body and in areas with high uptake of {sup 131}I. The total score was used in the calculation to obtain the percentage distribution of {sup 13I} in the organs of the patient. The results showed that there similarity on the biodistribution of {sup 131}I between pre-dose and post-dose PCI. Therefore, it was found that it is valuable images of PCI pre-dose therapy as a way to assist the nuclear medicine physician in choosing the best activity to be administered to the patient in order to minimize the dose to adjacent organs. (author)

  2. Radioiodinated benzodiazepines: agents for mapping glial tumors

    Energy Technology Data Exchange (ETDEWEB)

    Van Dort, M.E.; Ciliax, B.J.; Gildersleeve, D.L.; Sherman, P.S.; Rosenspire, K.C.; Young, A.B.; Junck, L.; Wieland, D.M.


    Two isomeric iodinated analogues of the peripheral benzodiazepine binding site (PBS) ligand Ro5-4864 have been synthesized and labeled in high specific activity with iodine-125. Competitive binding assays conducted with the unlabeled analogues indicate high affinity for PBS. Tissue biodistribution studies in rats with these /sup 125/I-labeled ligands indicate high uptake of radioactivity in the adrenals, heart, and kidney--tissues known to have high concentrations of PBS. Preadministration of the potent PBS antagonist PK 11195 blocked in vivo uptake in adrenal tissue by over 75%, but to a lesser degree in other normal tissues. In vivo binding autoradiography in brain conducted in C6 glioma bearing rats showed dense, PBS-mediated accumulation of radioactivity in the tumor. Ligand 6 labeled with /sup 123/I may have potential for scintigraphic localization of intracranial glioma.

  3. Identification of 200,000-dalton human cell surface protein encoded by gene mapped to long arm of chromosome 11. (United States)

    Imada, M; Kao, F T; Law, M L; Jones, C


    Cell surface proteins and glycoproteins of human and Chinese hamster cells and their hybrid cell clones were analyzed by two-dimensional gel electrophoresis. The J1 clone of human-Chinese hamster hybrid cells contained chromosome 11 as its only human chromosome. The J1 cells expressed a glycoprotein of 200,000 daltons which was shared by human fibroblasts but not by the parental Chinese hamster ovary cells. The 200,000-dalton protein was identified as a cell surface protein by the method of lactoperoxidase-catalyzed iodination. The protein was electrophoretically purified from radioiodinated cultures of human fibroblasts and J1 cells and subjected to the analysis of tryptic peptides by thin-layer electrophoresis followed by chromatography. The protein from both sources gave rise to fingerprints which closely resembled to each other. The results are consistent with a hypothesis that the 200,000-dalton protein of the J1 clone is of human origin. Analysis of segregant clones of J1 cells, which have deletions on human chromosome 11, has further suggested that the gene for this glycoprotein maps to the long arm of chromosome 11. A gene coding for the 200,000-dalton protein has not been previously mapped to this chromosome.

  4. Gene Ontology

    Directory of Open Access Journals (Sweden)

    Gaston K. Mazandu


    Full Text Available The wide coverage and biological relevance of the Gene Ontology (GO, confirmed through its successful use in protein function prediction, have led to the growth in its popularity. In order to exploit the extent of biological knowledge that GO offers in describing genes or groups of genes, there is a need for an efficient, scalable similarity measure for GO terms and GO-annotated proteins. While several GO similarity measures exist, none adequately addresses all issues surrounding the design and usage of the ontology. We introduce a new metric for measuring the distance between two GO terms using the intrinsic topology of the GO-DAG, thus enabling the measurement of functional similarities between proteins based on their GO annotations. We assess the performance of this metric using a ROC analysis on human protein-protein interaction datasets and correlation coefficient analysis on the selected set of protein pairs from the CESSM online tool. This metric achieves good performance compared to the existing annotation-based GO measures. We used this new metric to assess functional similarity between orthologues, and show that it is effective at determining whether orthologues are annotated with similar functions and identifying cases where annotation is inconsistent between orthologues.

  5. Dual effect of a polymorphism in the macrophage migration inhibitory factor gene is associated with new-onset Graves disease in a Taiwanese Chinese population.

    Directory of Open Access Journals (Sweden)

    Yu-Huei Liu

    Full Text Available Graves disease (GD is an autoimmune disease. Macrophage migration inhibitory factor (MIF is a potent cytokine that plays an important role in the regulation of immune responses. Two polymorphisms in the promoter region of MIF, rs5844572 and rs755622, are known to affect MIF expression. The purpose of this study was to investigate the relationship between polymorphisms in the MIF gene promoter and the severity of GD. A total of 677 individuals, including 481 GD patients and 196 ethnically matched healthy controls, were genotyped to identify differences in the distribution of the MIF polymorphisms rs5844572 and rs755622. Although there were no significant differences in the allele or genotype distributions among patients with different grades of goiter in GD and healthy controls, the distribution of the C allele, especially C/C genotype, of the rs755622 single nucleotide polymorphism (SNP in MIF, may be as a risk factor for goiter initiation whereas a protector against development of severe goiter in patients with untreated GD (p<0.05. A goiter-developmental model incorporating genetic (MIF SNP rs755622 and environmental risk factors (gender, radioiodine treatment, thyroid gland surgery and vitiligo significantly increased the prediction accuracy. Further studies are required to address the role of MIF polymorphisms, as well as their association with other candidate genes, in GD.

  6. Emerging comorbidities in Graves' disease patients treated with radioiodine with more than 10 years of follow-up; Avaliacao do surgimento de comorbidades em pacientes com doenca de Graves tratados com iodo radioativo em acompanhamento por mais de 10 anos

    Energy Technology Data Exchange (ETDEWEB)

    Azevedo, Fernanda Vieira Ramalho de; Blotta, Francisco Gomes da Silva; Goirgetta, Juliana Malheiros; Vaisman, Mario [Universidade Federal do Rio de Janeiro (HUCFF/UFRJ), RJ (Brazil). Hospital Universitario Clementino Fraga Filho. Faculdade de Medicina. Servico de Endocrinologia; Noe, Rosangela [Universidade Federal do Rio de Janeiro (HUCFF/UFRJ), RJ (Brazil). Bioestatistica da Divisao de Pesquisa


    Objectives: To evaluate the occurrence of cardiovascular disease and malignant tumors and the mortality rate in patients who received radioiodine treatment for hyperthyroidism due to Graves' disease with at least ten years of follow-up. Materials and methods: The medical records of all patients who were treated with I{sup 131} for Graves' disease at Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, were reviewed retrospectively, between January, 1981 and November, 1999. Results: Data from 107 patients (14 men and 93 women), with median age of 54 years were analyzed. Comparing the group of patients who were treated with I{sup 131} therapy with a group of euthyroid patients post-treatment with antithyroid drugs, a significant increase in the occurrence of hypertension and dyslipidemia was observed, but not in mortality rate. Conclusion: To evaluate the real influence of the treatment with radioactive iodine in the occurrence of these comorbidities and the mortality rate, we need a longer follow-up. The age and time of exposure to the effects of hyperthyroidism seem to influence the occurrence of these comorbidities. (author)

  7. Expression of the human monocyte membrane antigen gp55 by murine fibroblasts after DNA-mediated gene transfer. (United States)

    Ashmun, R A; Peiper, S C; Rebentisch, M B; Look, A T


    Human DNA sequences that contain the gene encoding gp55, a cell surface glycoprotein expressed exclusively on mature human monocytes and monocytic leukemia cells, were isolated in a mouse genetic background. DNA from mature human monocytes was cotransfected with DNA from a molecularly cloned feline sarcoma virus containing the v-fms oncogene into NIH-3T3 cells. Transformed mouse fibroblasts that expressed gp55, based on their reactivity with the MY4, B44.1, or LeuM3 monoclonal antibodies, were selected by fluorescence-activated cell sorting. Regardless of which antibody was used for selection, equivalent binding of all three antibodies was observed for positive transformants. Secondary and tertiary mouse cell transformants were obtained after additional rounds of transfection and cell sorting with the use of DNA from primary and then secondary transformants. Southern blot analysis of the cellular DNA from two independently derived tertiary subclones revealed a limited complement of human sequences, thus indicating that the gene encoding gp55 is included in fewer than 50 kilobases of human DNA. Independently derived tertiary subclones displayed concordant patterns of reactivity with 13 monocyte-specific monoclonal antibodies, thus indicating that each recognized an epitope on the product (gp55) of a single human gene. The 55-kilodalton cell surface polypeptide was specifically immunoprecipitated with a representative monoclonal antibody, 26if, from lysates of enzymatically radioiodinated peripheral blood monocytes and tertiary transformants. We conclude that gp55 is highly immunogenic and that a large number of independently derived monoclonal antibodies specific for human monocytes react with epitopes on this one molecule.

  8. Special Issue: Gene Conversion in Duplicated Genes

    Directory of Open Access Journals (Sweden)

    Hideki Innan


    Full Text Available Gene conversion is an outcome of recombination, causing non-reciprocal transfer of a DNA fragment. Several decades later than the discovery of crossing over, gene conversion was first recognized in fungi when non-Mendelian allelic distortion was observed. Gene conversion occurs when a double-strand break is repaired by using homologous sequences in the genome. In meiosis, there is a strong preference to use the orthologous region (allelic gene conversion, which causes non-Mendelian allelic distortion, but paralogous or duplicated regions can also be used for the repair (inter-locus gene conversion, also referred to as non-allelic and ectopic gene conversion. The focus of this special issue is the latter, interlocus gene conversion; the rate is lower than allelic gene conversion but it has more impact on phenotype because more drastic changes in DNA sequence are involved.

  9. Effects of DNA-targeted ionizing radiation produced by 5-[125I]iodo-2'-deoxyuridine on global gene expression in primary human cells

    Directory of Open Access Journals (Sweden)

    Panyutin Igor G


    Full Text Available Abstract Background This study assesses the whole-genome gene expression changes in a panel of primary human cell lines in response to DNA damage mediated by decay of DNA-incorporated radioiodinated thymidine analog 5-[125I]iodo-2'-deoxyuridine (125I-IUdR. Three normal human cell lines of different origin, namely, gingival fibroblasts AG09319, fetal skin fibroblasts GM05388 and neonatal foreskin epidermal keratinocytes (NHFK were used in this study. DNA molecules were radiolabeled by incubation of cells in culture in a medium supplemented with either 3.7 kBq/ml or 18.5 kBq/ml of 125I-IUdR for 24 h followed by incubation in IUdR-free medium for additional 24 hours. Each experiment was carried out in quadruplicate. 125I-IUdR uptake was monitored by measuring DNA-associated radioactivity. The whole-genome gene expression changes were evaluated using Agilent Human Whole Genome oligo microarrays containing 44,290 elements representing all known and predicted human genes. DNA microarray dataset was independently partially validated with quantitative real-time PCR (RT-PCR. Results AG09319 gingival cells in culture responded to 125I-IUdR treatment by changing the expression level of 335 genes in total, whereas under the same conditions GM05388 and NHFK cells differentially expressed 49 genes and 27 genes, respectively. However, for GM05388 cells the number of differentially expressed genes increases with the rise of 125I-IUdR concentrations in cell culture media. The key up-regulated biological processes in a chosen panel of cell lines concern the regulation of protein kinase activities and/or cell death. Genes repressed in response to 125I-IUdR treatment are involved in cytokinesis, M phase of the cell cycle, chromosome architecture and organization, DNA metabolism, DNA packaging, DNA repair and response to DNA damage. Despite the disparate nature of the gene patterns elicited by 125I-induced DNA damage among the different cell lines, the

  10. Essential Bacillus subtilis genes

    DEFF Research Database (Denmark)

    Kobayashi, K.; Ehrlich, S.D.; Albertini, A.


    To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were...

  11. Human Gene Therapy: Genes without Frontiers? (United States)

    Simon, Eric J.


    Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

  12. Genes and Hearing Loss (United States)

    ... Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient Health Information News media interested in ... One of the most common birth defects is hearing loss or deafness (congenital), which can affect as ...

  13. Epigenetics: beyond genes

    CSIR Research Space (South Africa)

    Fossey, A


    Full Text Available Gene regulatory processes lead to differential gene expression and are referred to as epigenetic phenomena; these are ubiquitous processes in the biological world. These reversible heritable changes concern DNA and RNA, their interactions...

  14. Polydactyly and genes

    National Research Council Canada - National Science Library

    Phadke, Shubha R; Sankar, V H


    .... A lot of information about genes involved in development is available now. Genetics of hand development and genes involved in polydactyly syndromes is discussed in this article as a prototype to know about genetics of malformations...

  15. Evolution of gene expression after gene amplification. (United States)

    Garcia, Nelson; Zhang, Wei; Wu, Yongrui; Messing, Joachim


    We took a rather unique approach to investigate the conservation of gene expression of prolamin storage protein genes across two different subfamilies of the Poaceae. We took advantage of oat plants carrying single maize chromosomes in different cultivars, called oat-maize addition (OMA) lines, which permitted us to determine whether regulation of gene expression was conserved between the two species. We found that γ-zeins are expressed in OMA7.06, which carries maize chromosome 7 even in the absence of the trans-acting maize prolamin-box-binding factor (PBF), which regulates their expression. This is likely because oat PBF can substitute for the function of maize PBF as shown in our transient expression data, using a γ-zein promoter fused to green fluorescent protein (GFP). Despite this conservation, the younger, recently amplified prolamin genes in maize, absent in oat, are not expressed in the corresponding OMAs. However, maize can express the oldest prolamin gene, the wheat high-molecular weight glutenin Dx5 gene, even when maize Pbf is knocked down (through PbfRNAi), and/or another maize transcription factor, Opaque-2 (O2) is knocked out (in maize o2 mutant). Therefore, older genes are conserved in their regulation, whereas younger ones diverged during evolution and eventually acquired a new repertoire of suitable transcriptional activators. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  16. How Genes Evolve

    Indian Academy of Sciences (India)

    evolutionary history of duplicated genes within a given lineage. The timings of gene duplication events can be inferred ... evolutionary history of the creatures in which various globin genes are found, the timings of the ..... But I cannot find heart to give any part of my life for money-making purposes ... : In 1901, one of the large ...

  17. Discovering genes underlying QTL

    Energy Technology Data Exchange (ETDEWEB)

    Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)


    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  18. Gene therapy in periodontics (United States)

    Chatterjee, Anirban; Singh, Nidhi; Saluja, Mini


    GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person's genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is ‘the use of genes as medicine’. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone. PMID:23869119

  19. Gene therapy: An overview

    Directory of Open Access Journals (Sweden)

    Sudip Indu


    Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.

  20. Modelling prokaryote gene content

    Directory of Open Access Journals (Sweden)

    Edward Susko


    Full Text Available The patchy distribution of genes across the prokaryotes may be caused by multiple gene losses or lateral transfer. Probabilistic models of gene gain and loss are needed to distinguish between these possibilities. Existing models allow only single genes to be gained and lost, despite the empirical evidence for multi-gene events. We compare birth-death models (currently the only widely-used models, in which only one gene can be gained or lost at a time to blocks models (allowing gain and loss of multiple genes within a family. We analyze two pairs of genomes: two E. coli strains, and the distantly-related Archaeoglobus fulgidus (archaea and Bacillus subtilis (gram positive bacteria. Blocks models describe the data much better than birth-death models. Our models suggest that lateral transfers of multiple genes from the same family are rare (although transfers of single genes are probably common. For both pairs, the estimated median time that a gene will remain in the genome is not much greater than the time separating the common ancestors of the archaea and bacteria. Deep phylogenetic reconstruction from sequence data will therefore depend on choosing genes likely to remain in the genome for a long time. Phylogenies based on the blocks model are more biologically plausible than phylogenies based on the birth-death model.

  1. Retrieval with gene queries

    Directory of Open Access Journals (Sweden)

    Srinivasan Padmini


    Full Text Available Abstract Background Accuracy of document retrieval from MEDLINE for gene queries is crucially important for many applications in bioinformatics. We explore five information retrieval-based methods to rank documents retrieved by PubMed gene queries for the human genome. The aim is to rank relevant documents higher in the retrieved list. We address the special challenges faced due to ambiguity in gene nomenclature: gene terms that refer to multiple genes, gene terms that are also English words, and gene terms that have other biological meanings. Results Our two baseline ranking strategies are quite similar in performance. Two of our three LocusLink-based strategies offer significant improvements. These methods work very well even when there is ambiguity in the gene terms. Our best ranking strategy offers significant improvements on three different kinds of ambiguities over our two baseline strategies (improvements range from 15.9% to 17.7% and 11.7% to 13.3% depending on the baseline. For most genes the best ranking query is one that is built from the LocusLink (now Entrez Gene summary and product information along with the gene names and aliases. For others, the gene names and aliases suffice. We also present an approach that successfully predicts, for a given gene, which of these two ranking queries is more appropriate. Conclusion We explore the effect of different post-retrieval strategies on the ranking of documents returned by PubMed for human gene queries. We have successfully applied some of these strategies to improve the ranking of relevant documents in the retrieved sets. This holds true even when various kinds of ambiguity are encountered. We feel that it would be very useful to apply strategies like ours on PubMed search results as these are not ordered by relevance in any way. This is especially so for queries that retrieve a large number of documents.

  2. Primetime for Learning Genes. (United States)

    Keifer, Joyce


    Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be "poised" for rapid response to activate or repress gene expression depending on environmental stimuli.

  3. Primetime for Learning Genes

    Directory of Open Access Journals (Sweden)

    Joyce Keifer


    Full Text Available Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF, by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be “poised” for rapid response to activate or repress gene expression depending on environmental stimuli.

  4. Viral gene therapy. (United States)

    Mancheño-Corvo, P; Martín-Duque, P


    Cancer is a multigenic disorder involving mutations of both tumor suppressor genes and oncogenes. A large body of preclinical data, however, has suggested that cancer growth can be arrested or reversed by treatment with gene transfer vectors that carry a single growth inhibitory or pro-apoptotic gene or a gene that can recruit immune responses against the tumor. Many of these gene transfer vectors are modified viruses. The ability for the delivery of therapeutic genes, made them desirable for engineering virus vector systems. The viral vectors recently in laboratory and clinical use are based on RNA and DNA viruses processing very different genomic structures and host ranges. Particular viruses have been selected as gene delivery vehicles because of their capacities to carry foreign genes and their ability to efficiently deliver these genes associated with efficient gene expression. These are the major reasons why viral vectors derived from retroviruses, adenovirus, adeno-associated virus, herpesvirus and poxvirus are employed in more than 70% of clinical gene therapy trials worldwide. Because these vector systems have unique advantages and limitations, each has applications for which it is best suited. Retroviral vectors can permanently integrate into the genome of the infected cell, but require mitotic cell division for transduction. Adenoviral vectors can efficiently deliver genes to a wide variety of dividing and nondividing cell types, but immune elimination of infected cells often limits gene expression in vivo. Herpes simplex virus can deliver large amounts of exogenous DNA; however, cytotoxicity and maintenance of transgene expression remain as obstacles. AAV also infects many non-dividing and dividing cell types, but has a limited DNA capacity. This review discusses current and emerging virusbased genetic engineering strategies for the delivery of therapeutic molecules or several approaches for cancer treatment.

  5. Imaging expression of adenoviral HSV1-tk suicide gene transfer using the nucleoside analogue FIRU

    Energy Technology Data Exchange (ETDEWEB)

    Nanda, Dharmin [Department of Neurology, Daniel den Hoed Cancer Centre, University Hospital Rotterdam (Netherlands); Department of Neurosurgery, University Hospital Rotterdam (Netherlands); Jong, Marion de; Bakker, Willem; Bijster, Magda; Cox, Peter [Department of Nuclear Medicine, University Hospital Rotterdam (Netherlands); Vogels, Ronald; Havenga, Menzo [Crucell Holland BV, Leiden (Netherlands); Driesse, Maarten; Avezaat, Cees [Department of Neurosurgery, University Hospital Rotterdam (Netherlands); Morin, Kevin; Naimi, Ebrahim; Knaus, Edward; Wiebe, Leonard [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton (Canada); Smitt, Peter Sillevis [Department of Neurology, Daniel den Hoed Cancer Centre, University Hospital Rotterdam (Netherlands)


    Substrates for monitoring HSV1-tk gene expression include uracil and acycloguanosine derivatives.The most commonly used uracil derivative to monitor HSV1-tk gene transfer is 1-(2-fluoro-2-deoxy-{beta}-D-arabinofuranosyl)-5-[*I]iodouracil (fialuridine; I*-FIAU), where the asterisk denotes any of the radioactive iodine isotopes that can be used. We have previously studied other nucleosides with imaging properties as good as or better than FIAU, including 1-(2-fluoro-2-deoxy-{beta}-D-ribofuranosyl)-5-[*I]iodouracil (FIRU). The first aim of this study was to extend the biodistribution data of {sup 123}I-labelled FIRU. Secondly, we assessed the feasibility of detecting differences in HSV1-tk gene expression levels following adenoviral gene transfer in vivo with {sup 123}I-FIRU. 9L rat gliosarcoma cells were stably transfected with the HSV1-tk gene (9L-tk+). {sup 123}I-FIRU was prepared by radioiodination of 1-(2-fluoro-2-deoxy-{beta}-D-ribofuranosyl)-5-tributylstannyl uracil (FTMRSU; precursor compound) and purified using an activated Sep-Pak column. Incubation of 9L-tk+ cells and the parental 9L cells with {sup 123}I-FIRU resulted in a 100-fold higher accumulation of radioactivity in the 9L-tk+ cells after an optimum incubation time of 4 h. NIH-bg-nu-xid mice were then inoculated subcutaneously with HSV1-tk (-) 9L cells or HSV1-tk (+) 9L-tk+ cells into both flanks. Biodistribution studies and gamma camera imaging were performed at 15 min and 1, 2, 4 and 24 h p.i. At 15 min, the tumour/muscle, tumour/blood and tumour/brain ratios were 5.2, 1.0 and 30.3 respectively. Rapid renal clearance of the tracer from the body resulted in increasing tumour/muscle, tumour/blood and tumour/brain ratios, reaching values of 32.2, 12.5 and 171.6 at 4 h p.i. A maximum specific activity of 22%ID/g tissue was reached in the 9L-tk+ tumours 4 h after {sup 123}I-FIRU injection. Two Ad5-based adenoviral vectors containing the HSV1-tk gene were constructed: a replication-incompetent vector with

  6. Gene manupulations in invertebrates


    Čermáková, Eliška


    Gene manipulations in invertebrates are based on the same approches used in vertebrates. The are applied for the development of new genotypes in model species, convenient as model systems of human hereditary diseases etc. Gene manipulations are important as well for practical purposes, which is shown by the example of trangenic mosquitoes. Recently, it has been proved that programmable nucleases can be successfully used in invertebrates. Key words: Gene manipulations, invertebrates, methods, ...

  7. Genes and Social Behavior


    Robinson, Gene E.; Fernald, Russell D.; Clayton, David F.


    What specific genes and regulatory sequences contribute to the organization and functioning of brain circuits that support social behavior? How does social experience interact with information in the genome to modulate these brain circuits? Here we address these questions by highlighting progress that has been made in identifying and understanding two key “vectors of influence” that link genes, brain, and social behavior: 1) social information alters gene readout in the brain to influence beh...

  8. History of gene therapy. (United States)

    Wirth, Thomas; Parker, Nigel; Ylä-Herttuala, Seppo


    Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Chromatin loops, gene positioning, and gene expression

    NARCIS (Netherlands)

    Holwerda, S.; de Laat, W.


    Technological developments and intense research over the last years have led to a better understanding of the 3D structure of the genome and its influence on genome function inside the cell nucleus. We will summarize topological studies performed on four model gene loci: the alpha- and beta-globin

  10. One gene's shattering effects. (United States)

    Olsen, Kenneth M


    A new study shows that three independent mutations in the Sh1 gene, which encodes a YABBY transcription factor, gave rise to the non-shattering seed phenotype in domesticated sorghum. This same gene may have also had a role in the domestication of other cereals, including maize and rice.

  11. Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy


    Wold, William S. M.; Toth, Karoly


    Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vector...

  12. Gene therapy flexes muscle. (United States)

    VandenDriessche, Thierry


    This commentary highlights the promising results of recent studies in animal models of Duchenne muscular dystrophy and amyotrophic lateral sclerosis that have clearly demonstrated the potential of gene therapy for tackling these diseases. In the absence of effective drugs or other treatments, these advances in gene therapy technology represent the best hope for those patients and families that are blighted by these diseases. Diseases characterized by progressive muscle degeneration are often incurable and affect a relatively large number of individuals. The progressive deterioration of muscle function is like the sword of Damocles that constantly reminds patients suffering from these diseases of their tragic fate, since most of them will eventually die from cardiac or pulmonary dysfunction. Some of these disorders are due to mutations in genes that directly influence the integrity of muscle fibers, such as in Duchenne muscular dystrophy (DMD), a recessive X-linked genetic disease. Others result from a progressive neurodegeneration of the motoneurons that are essential for maintaining muscle function, such as in amyotrophic lateral sclerosis (ALS), also commonly known as Lou Gehrig's disease. The genetic basis of DMD is relatively well understood as it is due to mutations in the dystrophin gene that encodes the cognate sarcolemmal protein. In contrast, the cause of ALS is poorly defined, with the exception of some dominantly inherited familial cases of ALS that are due to gain-of-function mutations in the gene encoding superoxide dismutase (SODG93A). Gene therapy for these disorders has been hampered by the inability to achieve widespread gene transfer. Moreover, since familial ALS is due to a dominant gain-of-function mutation, inhibition of gene expression (rather than gene augmentation) would be required to correct the phenotype, which is particularly challenging. Copyright (c) 2005 John Wiley & Sons, Ltd.

  13. Multinodular goiter treatment with radioiodine aided by recombinant human TSH in different doses: a randomized, double-blind, placebo-controlled study;Administracao previa do TSH humano recombinante, em diferentes doses, no tratamento do bocio multinodular com iodo radioativo: um estudo randomizado, duplo cego, controlado com placebo

    Energy Technology Data Exchange (ETDEWEB)

    Albino, Claudio Cordeiro


    Background: There is not an optimal treatment for multinodular goiter (MNG). Surgery is the main therapeutic option because it decreases thyroid volume, reduces compression symptoms and provide histological diagnosis. Radioiodine ({sup 131}I) is an efficient therapeutic option for the treatment of MNG mainly when surgery is not indicated or when the patient refused it. However, high activities of {sup 131}I are frequently required for clinically significant results. This procedure increases the body radiation exposure and the hospitalization costs. Recombinant human TSH (rh TSH) allows a reduction in the administered activity of {sup 131}I with effective thyroid volume (TV) reduction. However, this combination therapeutic can increase collateral effects. Objective: To evaluate the efficacy and safety of low and intermediate doses of rh TSH compared to placebo, associated with a fixed activity of {sup 131}I in MNG treatment. Patients and Methods: Thirty patients with MNG received 0.1 mg of rh TSH (group I, n=10), 0.01 mg of rh TSH (group II, n=10), or placebo (control group, n=10). After 24 hours, 30 mCi of {sup 131}I was given to all patients. Radioactive iodine uptake (RAIU) was determined before and 24 hours after rh TSH. Before and 2, 7, 180 and 360 days after the TV was measured by magnetic resonance image (MRI). The smallest cross-sectional area of tracheal lumen (Scat) was also measured with MRI before, 2 and 7 days after treatment. Antithyroid antibodies, TSH, T3 and free T4 were assessed regularly. Results: After 6 months, the decrease in TV was more significant in groups I (30.3 +- 16.5%) and II (22.6 +- 14.5%), than in control group (5.0 +- 14.6%; p=0.01). After 12 months, TV decreased more in group I (39.2 +- 16.9%) and group II (38.8 +- 24.4%) than in group III (23.4 +- 23.59%) but it was not statistically significant (p=0.205). During the first 30 days,total T3 and free T4 increased, without reaching thyrotoxic levels and TSH decreased. After 12 months

  14. Antisense gene silencing

    DEFF Research Database (Denmark)

    Nielsen, Troels T; Nielsen, Jørgen E


    Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied...... to mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how...

  15. Gene Therapy for Hemophilia. (United States)

    Nathwani, Amit C; Davidoff, Andrew M; Tuddenham, Edward G D


    The best currently available treatments for hemophilia A and B (factor VIII or factor IX deficiency, respectively) require frequent intravenous infusion of highly expensive proteins that have short half-lives. Factor levels follow a saw-tooth pattern that is seldom in the normal range and falls so low that breakthrough bleeding occurs. Most hemophiliacs worldwide do not have access to even this level of care. In stark contrast, gene therapy holds out the hope of a cure by inducing continuous endogenous expression of factor VIII or factor IX following transfer of a functional gene to replace the hemophilic patient's own defective gene. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Novel Functionalized Ceramic Getter Materials for Adsorption of Radioiodine

    Energy Technology Data Exchange (ETDEWEB)

    Mattigod, Shas V.; Fryxell, Glen E.; Parker, Kent E.; Kaplan, Daniel I.


    A new class of getter materials has been synthesized for immobilization of long-lived radionuclides such as 129I. These novel materials consist of nanoporous ceramic substrates with tailored pore sizes ranging from 2 – 20 nm. These high surface area (~1000 m2/g) ceramic substrates have been functionalized with self-assembled monolayers consisting of soft cation-capped thiol-functionality. The resulting getter materials exhibit highly dense binding sites, and excellent selectivity for iodide. The effectiveness of these novel getter materials was evaluated using radioiodide-spiked samples of surface water and concrete leachate and adsorption performance was compared with natural sulfide mineral getter materials. The data indicated that the novel getter materials have very high affinity for radioiodide (Kd: 4 x 104 – 3 x 105 ml/g and 6 x 105 ml/g in surface and concrete leachate respectively). Comparatively, the radioiodide Kd values for natural mineral getters were typically two to three orders magnitude less than the novel getters. The results indicated that the synthetic getter materials have the potential to immobilize and therefore retard the migration of 129I in the subsurface environment. Additional studies are being conducted to evaluate the long-term stability of these materials in waste disposal environments.

  17. Radioiodine therapy in skeletal metastases from well-differentiated ...

    African Journals Online (AJOL)

    Aim.The purpose of this study was to examine the outcome of patients with skeletal metastases from well-differentiated thyroid carcinoma and analyse the effect of variables that influence the prognosis of this disease. Method. We retrospectively reviewed 352 patients treated and followedup at the Charlotte Maxeke ...


    Energy Technology Data Exchange (ETDEWEB)

    Denham, M.; Kaplan, D.; Yeager, C.


    Iodine-129 ({sup 129}I) has not received as much attention in basic and applied research as other contaminants associated with DOE plumes. These other contaminants, such as uranium, plutonium, strontium, and technetium are more widespread and exist at more DOE facilities. Yet, at the Hanford Site and the Savannah River Site {sup 129}I occurs in groundwater at concentrations significantly above the primary drinking water standard and there is no accepted method for treating it, other than pump-and-treat systems. With the potential arrival of a 'Nuclear Renaissance', new nuclear power facilities will be creating additional {sup 129}I waste at a rate of 1 Ci/gigawatts energy produced. If all 22 proposed nuclear power facilities in the U.S. get approved, they will produce more {sup 129}I waste in seven years than presently exists at the two facilities containing the largest {sup 129}I inventories, ({approx}146 Ci {sup 129}I at the Hanford Site and the Savannah River Site). Hence, there is an important need to fully understand {sup 129}I behavior in the environment to clean up existing plumes and to support the expected future expansion of nuclear power production. {sup 129}I is among the key risk drivers at all DOE nuclear disposal facilities where {sup 129}I is buried, because of its long half-life (16 million years), high toxicity (90% of the body's iodine accumulates in the thyroid), high inventory, and perceived high mobility in the subsurface environment. Another important reason that {sup 129}I is a key risk driver is that there is the uncertainty regarding its biogeochemical fate and transport in the environment. We typically can define {sup 129}I mass balance and flux at sites, but can not accurately predict its response to changes in the environment. This uncertainty is in part responsible for the low drinking water standard, 1 pCi/L {sup 129}I, and the low permissible inventory limits (Ci) at the Savannah River Site, Hanford Site, and the former Yucca Mountain disposal facilities. The objectives of this report are to: (1) compile the background information necessary to understand behavior of {sup 129}I in the environment, (2) discuss sustainable remediation approaches to {sup 129}I contaminated groundwater, and (3) identify areas of research that will facilitate remediation of {sup 129}I contaminated areas on DOE sites. Lines of scientific inquiry that would significantly advance the goals of basic and applied research programs for accelerating {sup 129}I environmental remediation and reducing uncertainty associated with disposal of {sup 129}I waste are: (1) Evaluation of amendments or other treatment systems that can sequester subsurface groundwater {sup 129}I. (2) Develop analytical techniques for measurement of total {sup 129}I that eliminate the necessity of collecting and shipping large samples of groundwater. (3) Develop and evaluate ways to manipulate areas with organic-rich soil, such as wetlands, to maximize {sup 129}I sorption, minimizing releases during anoxic conditions. (4) Develop analytical techniques that can identify the various {sup 129}I species in the subsurface aqueous and solid phases at ambient concentrations and under ambient conditions. (5) Identify the mechanisms and factors controlling iodine-natural organic matter interactions at appropriate environmental concentrations. (6) Understand the biological processes that transform iodine species throughout different compartments of subsurface waste sites and the role that these processes have on {sup 129}I flux.

  19. Surface free energy analysis of adsorbents used for radioiodine adsorption

    Energy Technology Data Exchange (ETDEWEB)

    González-García, C.M. [Departamento de Física Aplicada, Universidad de Extremadura, Avda. Elvas s/n, 06006 Badajoz (Spain); Román, S., E-mail: [Departamento de Física Aplicada, Universidad de Extremadura, Avda. Elvas s/n, 06006 Badajoz (Spain); González, J.F.; Sabio, E. [Departamento de Física Aplicada, Universidad de Extremadura, Avda. Elvas s/n, 06006 Badajoz (Spain); Ledesma, B. [Departamento de Ingeniería Mecánica, Energética y de los Materiales, Universidad de Extremadura, Avda. Elvas s/n, 06006 Badajoz (Spain)


    In this work, the surface free energy of biomass-based activated carbons, both fresh and impregnated with triethylenediamine, has been evaluated. The contribution of Lifshitz van der Waals components was determined by the model proposed by van Oss et al. The results obtained allowed predicting the most probable configurations of the impregnant onto the carbon surface and its influence on the subsequent adsorption of radioactive methyl iodide.

  20. X-ray and radioiodine dose to thyroid follicular cells

    Energy Technology Data Exchange (ETDEWEB)

    Faw, R.E. (Kansas State Univ., Manhattan, KS (USA). Dept. of Nuclear Engineering); Eckerman, K.F.; Ryman, J.C. (Oak Ridge National Lab., TN (USA))


    Radiation doses to the epithelial cells of thyroid follicles have been calculated for internal exposure by radionuclides of iodine and by secondary radiations created as a result of interactions of externally administered x rays with iodine naturally occurring in the thyroid. Calculations were performed for the thyroids of subjects ranging from the newborn to the adult male. Results for internal radionuclides are reported as the dose rate to follicular-cell nuclei per unit specific activity of the radionuclide in the thyroid as a whole, i.e., as the specific S value'' as used in the MIRD method for internal dosimetry. Results for x rays are reported as the response function, i.e., the absorbed dose per unit fluence of primary x rays. Dose rates are subdivided into internal and external components, the former from radiations emitted within the colloid volume of any one follicle, and the latter from radiations emitted throughout the thyroid in follicles surrounding that one follicle. 37 refs., 5 figs., 3 tabs.


    African Journals Online (AJOL)

    Objectives. The aim of this study was to investigate effectiveness, action rate and eventual complications of radio- active iodine (RAJ) therapy in our patients with hyperthyroid Graves' disease. Design. Retrospective analysis of clinical results. Setting. Departments of Internal Medicine, Nuclear Medicine and Biostatistics at ...

  2. Polyacrylonitrile-Chalcogel Hybrid Sorbents for Radioiodine Capture

    Energy Technology Data Exchange (ETDEWEB)

    Brian J. Riley; David A. Pierce; Jaehun Chun; Josef Matyas; William C. Lepry; Troy G. Garn; Jack D. Law; Mercouri G. Kanatzidis


    Powders of a Sn2S3 chalcogen-based aerogel (chalcogel) were combined with powdered polyacrylonitrile (PAN) in different mass ratios (SnS33, SnS50, and SnS70; # = mass% of chalcogel), dissolved in dimethyl sulfoxide, and added dropwise to deionized water to form pellets of a porous PAN-chalcogel hybrid material. These pellets, along with pure powdered (SnSp) and granular (SnSg) forms of the chalcogel, were then used to capture iodine gas under both dynamic (dilute) and static (concentrated) conditions. Both SnSp and SnSg chalcogels showed very high iodine loadings at 67.2 and 68.3 mass%, respectively. The SnS50 hybrid sorbent demonstrated a high, although slightly reduced, maximum iodine loading (53.5 mass%) with greatly improved mechanical rigidity. In all cases, X-ray diffraction results showed the formation of crystalline SnI4 and SnI4(S8)2, revealing that the iodine binding in these materials is mainly due to a chemisorption process, although a small amount of physisorption was observed.

  3. Polyacrylonitrile-Chalcogel Hybrid Sorbents for Radioiodine Capture

    Energy Technology Data Exchange (ETDEWEB)

    Riley, Brian J.; Pierce, David A.; Chun, Jaehun; Matyas, Josef; Lepry, William C.; Garn, Troy; Law, Jack; Kanatzidis, Mercouri G.


    Powders of a Sn2S3 chalcogen-based aerogel (chalcogel) were combined with powdered polyacrylonitrile (PAN) in different mass ratios (SnS33, SnS50, and SnS70 in mass% of chalcogel), dissolved into dimethyl sulfoxide, and dropped into deionized water to form pellets of a porous PAN-chalcogel hybrid material. Pellets of these hybrid sorbents, along with pure powdered (SnSp) and granular (SnSg) forms of the chalcogel, were then used to adsorb iodine gas under both concentrated and dilute conditions. Both the SnSp and SnSg chalcogels showed very high maximum iodine loadings at 67.2 and 68.3 mass%. The maximum iodine loadings in the SnS33 and SnS50 were high at 32.8 and 53.5 mass%. In all cases, X-ray diffraction results showed the formation of Sn-I phases of SnI4 and SnI4(S8)2 revealing that the iodine binding in these materials is mainly due to a chemisorption process although some evidence also exists that supports a physisorption process.

  4. Genes underlying altruism. (United States)

    Thompson, Graham J; Hurd, Peter L; Crespi, Bernard J


    William D. Hamilton postulated the existence of 'genes underlying altruism', under the rubric of inclusive fitness theory, a half-century ago. Such genes are now poised for discovery. In this article, we develop a set of intuitive criteria for the recognition and analysis of genes for altruism and describe the first candidate genes affecting altruism from social insects and humans. We also provide evidence from a human population for genetically based trade-offs, underlain by oxytocin-system polymorphisms, between alleles for altruism and alleles for non-social cognition. Such trade-offs between self-oriented and altruistic behaviour may influence the evolution of phenotypic diversity across all social animals.

  5. Gene Expression Omnibus (GEO) (United States)

    U.S. Department of Health & Human Services — Gene Expression Omnibus is a public functional genomics data repository supporting MIAME-compliant submissions of array- and sequence-based data. Tools are provided...

  6. Evidence for homosexuality gene

    Energy Technology Data Exchange (ETDEWEB)

    Pool, R.


    A genetic analysis of 40 pairs of homosexual brothers has uncovered a region on the X chromosome that appears to contain a gene or genes for homosexuality. When analyzing the pedigrees of homosexual males, the researcheres found evidence that the trait has a higher likelihood of being passed through maternal genes. This led them to search the X chromosome for genes predisposing to homosexuality. The researchers examined the X chromosomes of pairs of homosexual brothers for regions of DNA that most or all had in common. Of the 40 sets of brothers, 33 shared a set of five markers in the q28 region of the long arm of the X chromosome. The linkage has a LOD score of 4.0, which translates into a 99.5% certainty that there is a gene or genes in this area that predispose males to homosexuality. The chief researcher warns, however, that this one site cannot explain all instances of homosexuality, since there were some cases where the trait seemed to be passed paternally. And even among those brothers where there was no evidence that the trait was passed paternally, seven sets of brothers did not share the Xq28 markers. It seems likely that homosexuality arises from a variety of causes.

  7. Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer

    National Research Council Canada - National Science Library

    Adegoke, Olufemi


    The objective of this CDA is to evaluate the gene-gene and gene-environment interactions in the etiology of breast cancer in two ongoing case-control studies, the Shanghai Breast Cancer Study (SBCS...

  8. The Mycoplasma hominis vaa gene displays a mosaic gene structure

    DEFF Research Database (Denmark)

    Boesen, Thomas; Emmersen, Jeppe M. G.; Jensen, Lise T.


    Mycoplasma hominis contains a variable adherence-associated (vaa) gene. To classify variants of the vaa genes, we examined 42 M. hominis isolated by PCR, DNA sequencing and immunoblotting. This uncovered the existence of five gene categories. Comparison of the gene types revealed a modular...

  9. Ribosomal genes in focus (United States)

    Koberna, Karel; Malínský, Jan; Pliss, Artem; Mašata, Martin; Večeřová, Jaromíra; Fialová, Markéta; Bednár, Jan; Raška, Ivan


    T he organization of transcriptionally active ribosomal genes in animal cell nucleoli is investigated in this study in order to address the long-standing controversy with regard to the intranucleolar localization of these genes. Detailed analyses of HeLa cell nucleoli include direct localization of ribosomal genes by in situ hybridization and their indirect localization via nascent ribosomal transcript mappings. On the light microscopy (LM) level, ribosomal genes map in 10–40 fluorescence foci per nucleus, and transcription activity is associated with most foci. We demonstrate that each nucleolar focus observed by LM corresponds, on the EM level, to an individual fibrillar center (FC) and surrounding dense fibrillar components (DFCs). The EM data identify the DFC as the nucleolar subcompartment in which rRNA synthesis takes place, consistent with detection of rDNA within the DFC. The highly sensitive method for mapping nascent transcripts in permeabilized cells on ultrastructural level provides intense and unambiguous clustered immunogold signal over the DFC, whereas very little to no label is detected over the FC. This signal is strongly indicative of nascent “Christmas trees” of rRNA associated with individual rDNA genes, sampled on the surface of thin sections. Stereological analysis of the clustered transcription signal further suggests that these Christmas trees may be contorted in space and exhibit a DNA compaction ratio on the order of 4–5.5. PMID:12034768

  10. On sports and genes. (United States)

    Zilberman-Schapira, Gili; Chen, Jieming; Gerstein, Mark


    Our genes influence our athletic ability. However, the causal genetic factors and mechanisms, and the extent of their effects, remain largely elusive. Many studies investigate this association between specific genes and athletic performance. Such studies have increased in number over the past few years, as recent developments and patents in DNA sequencing have made large amounts of sequencing data available for such analysis. In this paper, we consider four of the most intensively studied genes in relation to athletic ability: angiotensin I-converting enzyme, alpha-actinin 3, peroxismose proliferator-activator receptor alpha and nitric oxide synthase 3. We investigate the connection between genotype and athletic phenotype in the context of these four genes in various sport fields and across different ethnicities and genders. We do an extensive literature survey on these genes and the polymorphisms (single nucleotide polymorphisms or indels) found to be associated with athletic performance. We also present, for each of these polymorphisms, the allele frequencies in the different ethnicities reported in the pilot phase of the 1000 Genomes Project - arguably the largest human genome-sequencing endeavor to date. We discuss the considerable success, and significant drawbacks, of past research along these lines, and propose interesting directions for future research.

  11. Recombination in immunoglobulin gene loci

    Directory of Open Access Journals (Sweden)

    Komisarenko S. V.


    Full Text Available Gene network of the lymphoid cell differentiation coordinates precisely the recombination process in immunoglobulin gene loci. In our opinion, cellular microRNAs can contribute to the allelic exclusion through microRNA-directed DNA methylation and participate in retargeting recombinases activity from the gene loci of heavy immunoglobulin chains to the gene loci of light chains

  12. Gene therapy prospects--intranasal delivery of therapeutic genes. (United States)

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej


    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  13. Gene decay in archaea

    Directory of Open Access Journals (Sweden)

    M. W. J. van Passel


    Full Text Available The gene-dense chromosomes of archaea and bacteria were long thought to be devoid of pseudogenes, but with the massive increase in available genome sequences, whole genome comparisons between closely related species have identified mutations that have rendered numerous genes inactive. Comparative analyses of sequenced archaeal genomes revealed numerous pseudogenes, which can constitute up to 8.6% of the annotated coding sequences in some genomes. The largest proportion of pseudogenes is created by gene truncations, followed by frameshift mutations. Within archaeal genomes, large numbers of pseudogenes contain more than one inactivating mutation, suggesting that pseudogenes are deleted from the genome more slowly in archaea than in bacteria. Although archaea seem to retain pseudogenes longer than do bacteria, most archaeal genomes have unique repertoires of pseudogenes.

  14. Mechanisms of Horizontal Gene Transfer


    Cafini Barrado, Fabio; Medrano Romero, Verónica; Morikawa, Kazuya


    Horizontal gene transfer plays important roles in the evolution of S. aureus, and indeed, a variety of virulence factors and antibiotic resistance genes are embedded in a series of mobile genetic elements. In this chapter, we review the mechanisms of horizontal gene transfer, including recent findings on the natural genetic competence. Then, we consider the transfer of two important antibiotic resistance genes: the methicillin resistance gene, mecA (in Staphylococcal Cassette Chromosome) and ...

  15. Idiomatic (gene) expressions. (United States)

    Rockman, Matthew V


    Hidden among the myriad nucleotide variants that constitute each species' gene pool are a few variants that contribute to phenotypic variation. Many of these differences that make a difference are non-coding cis-regulatory variants, which, unlike coding variants, can only be identified through laborious experimental analysis. Recently, Cowles et al.1 described a screening method that does an end-run around this problem by searching for genes whose cis regulation varies without having to find the polymorphic nucleotides that influence transcription. While we will continue to require a diverse arsenal of experimental methods, this versatile method will speed the identification of functional genetic variation. Copyright 2003 Wiley Periodicals, Inc.

  16. A Bayesian approach to gene-gene and gene-environment interactions in chronic fatigue syndrome. (United States)

    Lin, Eugene; Hsu, Sen-Yen


    In the study of genomics, it is essential to address gene-gene and gene-environment interactions for describing the complex traits that involves disease-related mechanisms. In this work, our goal is to detect gene-gene and gene-environment interactions resulting from the analysis of chronic fatigue syndrome patients' genetic and demographic factors including SNPs, age, gender and BMI. We employed the dataset that was original to the previous study by the Centers for Disease Control and Prevention Chronic Fatigue Syndrome Research Group. To investigate gene-gene and gene-environment interactions, we implemented a Bayesian based method for identifying significant interactions between factors. Here, we employed a two-stage Bayesian variable selection methodology based on Markov Chain Monte Carlo approaches. By applying our Bayesian based approach, NR3C1 was found in the significant two-locus gene-gene effect model, as well as in the significant two-factor gene-environment effect model. Furthermore, a significant gene-environment interaction was identified between NR3C1 and gender. These results support the hypothesis that NR3C1 and gender may play a role in biological mechanisms associated with chronic fatigue syndrome. We demonstrated that our Bayesian based approach is a promising method to assess the gene-gene and gene-environment interactions in chronic fatigue syndrome patients by using genetic factors, such as SNPs, and demographic factors such as age, gender and BMI.

  17. Neighboring Genes Show Correlated Evolution in Gene Expression (United States)

    Ghanbarian, Avazeh T.; Hurst, Laurence D.


    When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543

  18. Gene Therapy and Children (For Parents) (United States)

    ... Needs a Kidney Transplant Vision Facts and Myths Gene Therapy and Children KidsHealth > For Parents > Gene Therapy and ... by a "bad" gene. continue Two Types of Gene Therapy The two forms of gene therapy are: Somatic ...

  19. Ultrasound mediated gene transfection (United States)

    Williamson, Rene G.; Apfel, Robert E.; Brandsma, Janet L.


    Gene therapy is a promising modality for the treatment of a variety of human diseases both inherited and acquired, such as cystic fibrosis and cancer. The lack of an effective, safe method for the delivery of foreign genes into the cells, a process known as transfection, limits this effort. Ultrasound mediated gene transfection is an attractive method for gene delivery since it is a noninvasive technique, does not introduce any viral particles into the host and can offer very good temporal and spatial control. Previous investigators have shown that sonication increases transfection efficiency with and without ultrasound contrast agents. The mechanism is believed to be via a cavitation process where collapsing bubble nuclei permeabilize the cell membrane leading to increased DNA transfer. The research is focused on the use of pulsed wave high frequency focused ultrasound to transfect DNA into mammalian cells in vitro and in vivo. A better understanding of the mechanism behind the transfection process is also sought. A summary of some in vitro results to date will be presented, which includes the design of a sonication chamber that allows us to model the in vivo case more accurately.

  20. What is a Gene?

    Indian Academy of Sciences (India)

    His other interests include reading, photography and listening to classical music. The first part of this general article appeared in April 1997. S C Lakhotia. The first part of this article traced the evolution of the concept of a gene from Mendel's times to the middle of this century: starting from the imaginary factors of Mendel, the.

  1. Genes in mammalian reproduction

    Energy Technology Data Exchange (ETDEWEB)

    Gwatkin, R.B.L. [ed.


    This is an informative book which deals mainly with genomic imprinting, the role of steroid hormones in development, the expression of a variety of genes during development and the link to hereditary diseases. It is an up-to-date review in a field that is quickly changing and provides valuable basic information and current research trends.

  2. (FIE) gene from soybean

    African Journals Online (AJOL)



    Apr 17, 2012 ... Harb. Protoc. doi:10.1101/pdb.prot4666. Xu H, Li Y, Yan Y, Wang K, Gao Y, Hu Y (2010). Genome-scale identification of Soybean BURP domain-containing genes and their expression under stress treatments. BMC Plant Biol. 10: 197. Yadegari R, Kinoshita T, Lotan O, Cohen G, Katz A, Choi Y, Nakashima.

  3. Silence of the Genes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 12; Issue 4. Silence of the Genes - 2006 Nobel Prize in Physiology or Medicine. Utpal Nath Saumitra Das. General Article Volume 12 Issue 4 April 2007 pp 6-18. Fulltext. Click here to view fulltext PDF. Permanent link:

  4. Silence of the Genes

    Indian Academy of Sciences (India)


    research for several decades (See Resonance, Vol. 12, pp.47–53,. March 2007). RNA interference (RNAi) is a novel mechanism for controlling gene expression. In this mechanism, tiny double-stranded RNA molecules called 'small interfering RNA' (siRNA) degrade cellu- lar mRNA that has sequence similarity with them.

  5. Gene therapy in pancreatic cancer (United States)

    Liu, Si-Xue; Xia, Zhong-Sheng; Zhong, Ying-Qiang


    Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC by searching the literature published in English using the PubMed database and analyzing clinical trials registered on the Gene Therapy Clinical Trials Worldwide website (http://www. clinical). Viral vectors are main gene delivery tools in gene therapy of cancer, and especially, oncolytic virus shows brighter prospect due to its tumor-targeting property. Efficient therapeutic targets for gene therapy include tumor suppressor gene p53, mutant oncogene K-ras, anti-angiogenesis gene VEGFR, suicide gene HSK-TK, cytosine deaminase and cytochrome p450, multiple cytokine genes and so on. Combining different targets or combination strategies with traditional chemoradiotherapy may be a more effective approach to improve the efficacy of cancer gene therapy. Cancer gene therapy is not yet applied in clinical practice, but basic and clinical studies have demonstrated its safety and clinical benefits. Gene therapy will be a new and promising field for the treatment of PC. PMID:25309069

  6. Genes2FANs: connecting genes through functional association networks

    Directory of Open Access Journals (Sweden)

    Dannenfelser Ruth


    Full Text Available Abstract Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs, researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our

  7. Using gene expression noise to understand gene regulation

    NARCIS (Netherlands)

    Munsky, B.; Neuert, G.; van Oudenaarden, A.


    Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a

  8. Gene set analysis for longitudinal gene expression data

    Directory of Open Access Journals (Sweden)

    Piepho Hans-Peter


    Full Text Available Abstract Background Gene set analysis (GSA has become a successful tool to interpret gene expression profiles in terms of biological functions, molecular pathways, or genomic locations. GSA performs statistical tests for independent microarray samples at the level of gene sets rather than individual genes. Nowadays, an increasing number of microarray studies are conducted to explore the dynamic changes of gene expression in a variety of species and biological scenarios. In these longitudinal studies, gene expression is repeatedly measured over time such that a GSA needs to take into account the within-gene correlations in addition to possible between-gene correlations. Results We provide a robust nonparametric approach to compare the expressions of longitudinally measured sets of genes under multiple treatments or experimental conditions. The limiting distributions of our statistics are derived when the number of genes goes to infinity while the number of replications can be small. When the number of genes in a gene set is small, we recommend permutation tests based on our nonparametric test statistics to achieve reliable type I error and better power while incorporating unknown correlations between and within-genes. Simulation results demonstrate that the proposed method has a greater power than other methods for various data distributions and heteroscedastic correlation structures. This method was used for an IL-2 stimulation study and significantly altered gene sets were identified. Conclusions The simulation study and the real data application showed that the proposed gene set analysis provides a promising tool for longitudinal microarray analysis. R scripts for simulating longitudinal data and calculating the nonparametric statistics are posted on the North Dakota INBRE website Raw microarray data is available in Gene Expression Omnibus (National Center for Biotechnology Information with

  9. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis (United States)

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana


    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis. PMID:26393928

  10. Genes, stress, and depression. (United States)

    Wurtman, Richard J


    A relationship between genetic makeup and susceptibility to major depressive disorder (MDD) has long been suspected on the basis of family and twin studies. A metaanalysis of reports on the basis of twin studies has estimated MDD's degree of heritability to be 0.33 (confidence interval, 0.26-0.39). Among families exhibiting an increased prevalence of MDD, risk of developing the illness was enhanced in members exposed to a highly stressful environment. Aberrant genes can predispose to depression in a number of ways, for example, by diminishing production of growth factors that act during brain development. An aberrant gene could also increase or decrease a neurotransmitter's release into synapses, its actions, or its duration of activity. The gene products of greatest interest at present are those involved in the synthesis and actions of serotonin; among them, the serotonin-uptake protein localized within the terminals and dendrites of serotonin-releasing neurons. It has been found that the Vmax of platelet serotonin uptake is low in some patients with MDD; also, Vmax is highly correlated in twins. Antidepressant drugs such as the selective serotonin reuptake inhibitors act on this uptake protein. The specific genetic locus causing serotonin uptake to be lower in some patients with major depression involves a polymorphic region (5-HTTLPR) in the promoter region of the gene for the uptake protein. The gene itself exists as several alleles, the short "S" allele and the long "L" allele. The S variant is associated with less, and the L variant with more, of the uptake protein. The effect of stressful life events on depressive symptoms in young adults was found to be significantly stronger among SS or SL subjects than among LL subjects. Neuroimaging studies showed that people with the SS or SL alleles exhibited a greater activation of the amygdala in response to fearful stimuli than those with LL. It has been reported recently that mutations in the gene that controls

  11. Vertebrate gene predictions and the problem of large genes

    DEFF Research Database (Denmark)

    Wang, Jun; Li, ShengTing; Zhang, Yong


    To find unknown protein-coding genes, annotation pipelines use a combination of ab initio gene prediction and similarity to experimentally confirmed genes or proteins. Here, we show that although the ab initio predictions have an intrinsically high false-positive rate, they also have a consistent...

  12. Gene Therapy for Lung Cancer. (United States)

    Lara-Guerra, Humberto; Roth, Jack A


    Gene therapy was originally conceived to treat monogenic diseases. The replacement of a defective gene with a functional gene can theoretically cure the disease. In cancer, multiple genetic defects are present and the molecular profile changes during the course of the disease, making the replacement of all defective genes impossible. To overcome these difficulties, various gene therapy strategies have been adopted, including immune stimulation, transfer of suicide genes, inhibition of driver oncogenes, replacement of tumor-suppressor genes that could mediate apoptosis or anti-angiogenesis, and transfer of genes that enhance conventional treatments such as radiotherapy and chemotherapy. Some of these strategies have been tested successfully in non-small-cell lung cancer patients and the results of laboratory studies and clinical trials are reviewed herein.

  13. Gene therapy in keratoconus

    Directory of Open Access Journals (Sweden)

    Mahgol Farjadnia


    Full Text Available Keratoconus (KC is the most common ectasia of the cornea and is a common reason for corneal transplant. Therapeutic strategies that can arrest the progression of this disease and modify the underlying pathogenesis are getting more and more popularity among scientists. Cumulating data represent strong evidence of a genetic role in the pathogenesis of KC. Different loci have been identified, and certain mutations have also been mapped for this disease. Moreover, Biophysical properties of the cornea create an appropriate candidate of this tissue for gene therapy. Immune privilege, transparency and ex vivo stability are among these properties. Recent advantage in vectors, besides the ability to modulate the corneal milieu for accepting the target gene for a longer period and fruitful translation, make a big hope for stupendous results reasonable.

  14. The sulfatase gene family. (United States)

    Parenti, G; Meroni, G; Ballabio, A


    During the past few years, molecular analyses have provided important insights into the biochemistry and genetics of the sulfatase family of enzymes, identifying the molecular bases of inherited diseases caused by sulfatase deficiencies. New members of the sulfatase gene family have been identified in man and other species using a genomic approach. These include the gene encoding arylsulfatase E, which is involved in X-linked recessive chondrodysplasia punctata, a disorder of cartilage and bone development. Another important breakthrough has been the discovery of the biochemical basis of multiple sulfatase deficiency, an autosomal recessive disorder characterized by a severe of all sulfatase activities. These discoveries, together with the resolution of the crystallographic structure of sulfatases, have improved our understanding of the function and evolution of this fascinating family of enzymes.

  15. Brains, Genes and Primates (United States)

    Belmonte, Juan Carlos Izpisua; Callaway, Edward M.; Churchland, Patricia; Caddick, Sarah J.; Feng, Guoping; Homanics, Gregg E.; Lee, Kuo-Fen; Leopold, David A.; Miller, Cory T.; Mitchell, Jude F.; Mitalipov, Shoukhrat; Moutri, Alysson R.; Movshon, J. Anthony; Okano, Hideyuki; Reynolds, John H.; Ringach, Dario; Sejnowski, Terrence J.; Silva, Afonso C.; Strick, Peter L.; Wu, Jun; Zhang, Feng


    One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward. PMID:25950631

  16. PRRT2 gene mutations (United States)

    Gardiner, Alice R.; Bhatia, Kailash P.; Stamelou, Maria; Dale, Russell C.; Kurian, Manju A.; Schneider, Susanne A.; Wali, G.M.; Counihan, Tim; Schapira, Anthony H.; Spacey, Sian D.; Valente, Enza-Maria; Silveira-Moriyama, Laura; Teive, Hélio A.G.; Raskin, Salmo; Sander, Josemir W.; Lees, Andrew; Warner, Tom; Kullmann, Dimitri M.; Wood, Nicholas W.; Hanna, Michael


    ABSTRACT Objective: The proline-rich transmembrane protein (PRRT2) gene was recently identified using exome sequencing as the cause of autosomal dominant paroxysmal kinesigenic dyskinesia (PKD) with or without infantile convulsions (IC) (PKD/IC syndrome). Episodic neurologic disorders, such as epilepsy, migraine, and paroxysmal movement disorders, often coexist and are thought to have a shared channel-related etiology. To investigate further the frequency, spectrum, and phenotype of PRRT2 mutations, we analyzed this gene in 3 large series of episodic neurologic disorders with PKD/IC, episodic ataxia (EA), and hemiplegic migraine (HM). Methods: The PRRT2 gene was sequenced in 58 family probands/sporadic individuals with PKD/IC, 182 with EA, 128 with HM, and 475 UK and 96 Asian controls. Results: PRRT2 genetic mutations were identified in 28 out of 58 individuals with PKD/IC (48%), 1/182 individuals with EA, and 1/128 individuals with HM. A number of loss-of-function and coding missense mutations were identified; the most common mutation found was the p.R217Pfs*8 insertion. Males were more frequently affected than females (ratio 52:32). There was a high proportion of PRRT2 mutations found in families and sporadic cases with PKD associated with migraine or HM (10 out of 28). One family had EA with HM and another large family had typical HM alone. Conclusions: This work expands the phenotype of mutations in the PRRT2 gene to include the frequent occurrence of migraine and HM with PKD/IC, and the association of mutations with EA and HM and with familial HM alone. We have also extended the PRRT2 mutation type and frequency in PKD and other episodic neurologic disorders. PMID:23077024

  17. Gene Porter Bridwell (United States)


    Gene Porter Bridwell served as the director of the Marshall Space Flight Center from January 6, 1994 until February 3, 1996, when he retired from NASA after thirty-four years service. Bridwell, a Marshall employee since 1962, had been Marshall's Space Shuttle Projects Office Director and Space Station Redesign Team deputy manager. Under Bridwell, Marshall worked to develop its role as a Center of Excellence for propulsion and for providing access to space.

  18. Genealogy and gene trees. (United States)

    Rasmuson, Marianne


    Heredity can be followed in persons or in genes. Persons can be identified only a few generations back, but simplified models indicate that universal ancestors to all now living persons have occurred in the past. Genetic variability can be characterized as variants of DNA sequences. Data are available only from living persons, but from the pattern of variation gene trees can be inferred by means of coalescence models. The merging of lines backwards in time leads to a MRCA (most recent common ancestor). The time and place of living for this inferred person can give insights in human evolutionary history. Demographic processes are incorporated in the model, but since culture and customs are known to influence demography the models used ought to be tested against available genealogy. The Icelandic data base offers a possibility to do so and points to some discrepancies. Mitochondrial DNA and Y chromosome patterns give a rather consistent view of human evolutionary history during the latest 100 000 years but the earlier epochs of human evolution demand gene trees with longer branches. The results of such studies reveal as yet unsolved problems about the sources of our genome.

  19. Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.

    Directory of Open Access Journals (Sweden)

    Ming-Wei Su

    Full Text Available BACKGROUND: The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 single-nucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1, the gene coding interleukin-4 receptor alpha chain (IL4Ra and the gene coding insulin induced gene 2 (INSIG2 on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83% with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2, signal transducer and activator of transcription 6 (STAT6. We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest that GSTP1, INSIG2 and IL4Ra may influence the lifetime asthma susceptibility through gene-gene interactions in schoolchildren. Home dampness combined with each one of the genes STAT6, IL13 and ADRB2 could raise the asthma risk.

  20. Gene therapy of cancer and development of therapeutic target gene

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Min; Kwon, Hee Chung


    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene.

  1. Independent Gene Discovery and Testing (United States)

    Palsule, Vrushalee; Coric, Dijana; Delancy, Russell; Dunham, Heather; Melancon, Caleb; Thompson, Dennis; Toms, Jamie; White, Ashley; Shultz, Jeffry


    A clear understanding of basic gene structure is critical when teaching molecular genetics, the central dogma and the biological sciences. We sought to create a gene-based teaching project to improve students' understanding of gene structure and to integrate this into a research project that can be implemented by instructors at the secondary level…

  2. Gene probes: principles and protocols

    National Research Council Canada - National Science Library

    Rapley, Ralph; Aquino de Muro, Marilena


    ... of labeled DNA has allowed genes to be mapped to single chromosomes and in many cases to a single chromosome band, promoting significant advance in human genome mapping. Gene Probes: Principles and Protocols presents the principles for gene probe design, labeling, detection, target format, and hybridization conditions together with detailed protocols, accom...

  3. Compositional gradients in Gramineae genes

    DEFF Research Database (Denmark)

    Wong, Gane Ka-Shu; Wang, Jun; Tao, Lin


    In this study, we describe a property of Gramineae genes, and perhaps all monocot genes, that is not observed in eudicot genes. Along the direction of transcription, beginning at the junction of the 5'-UTR and the coding region, there are gradients in GC content, codon usage, and amino-acid usage...

  4. Optimal gene partition into operons correlates with gene functional order (United States)

    Zaslaver, Alon; Mayo, Avi; Ronen, Michal; Alon, Uri


    Gene arrangement into operons varies between bacterial species. Genes in a given system can be on one operon in some organisms and on several operons in other organisms. Existing theories explain why genes that work together should be on the same operon, since this allows for advantageous lateral gene transfer and accurate stoichiometry. But what causes the frequent separation into multiple operons of co-regulated genes that act together in a pathway? Here we suggest that separation is due to benefits made possible by differential regulation of each operon. We present a simple mathematical model for the optimal distribution of genes into operons based on a balance of the cost of operons and the benefit of regulation that provides 'just-when-needed' temporal order. The analysis predicts that genes are arranged such that genes on the same operon do not skip functional steps in the pathway. This prediction is supported by genomic data from 137 bacterial genomes. Our work suggests that gene arrangement is not only the result of random historical drift, genome re-arrangement and gene transfer, but has elements that are solutions of an evolutionary optimization problem. Thus gene functional order may be inferred by analyzing the operon structure across different genomes.

  5. Somatic gene therapy for dyslipidemias. (United States)

    Belalcazar, M; Chan, L


    Somatic gene transfer is a valuable tool for the in vivo evaluation of lipoprotein metabolism. It has been used to dissect metabolic pathways, to establish structure-function relationships of various gene products, and to evaluate conventional lipid-lowering and novel therapeutic genes for the treatment of lipoprotein disorders. In this article we review some general aspects of somatic gene therapy and the different vehicles used for the delivery of therapeutic genes. We highlight some recent advances in adenoviral vector development that make this vector an attractive system for clinical trials.

  6. Gene electrotransfer in clinical trials

    DEFF Research Database (Denmark)

    Gehl, Julie


    Electroporation is increasingly being used for delivery of chemotherapy to tumors. Likewise, gene delivery by electroporation is rapidly gaining momentum for both vaccination purposes and for delivery of genes coding for other therapeutic molecules, such as chronic diseases or cancer. This chapte...... describes how gene therapy may be performed using electric pulses to enhance uptake and expression.......Electroporation is increasingly being used for delivery of chemotherapy to tumors. Likewise, gene delivery by electroporation is rapidly gaining momentum for both vaccination purposes and for delivery of genes coding for other therapeutic molecules, such as chronic diseases or cancer. This chapter...

  7. Tumor-suppressing gene therapy. (United States)

    Fang, Bingliang; Roth, Jack A


    Tumor-suppressor genes play pivotal roles in maintaining genome integrity and in regulating cell proliferation, differentiation, and apoptosis. Their loss-of-function mutations are related directly to tumorigenesis. Thus, use of tumor-suppressor genes as anticancer therapeutics has been investigated rigorously in both experimental and clinical researches. Transfer of various tumor-suppressor genes directly to cancer cells has been demonstrated to suppress tumor growth via induction of apoptosis and cell-cycle arrest and, in some cases, with evidence for bystander effects. Various studies also have shown that combination of tumor-suppressor gene therapy with conventional anticancer therapy can yield synergistic therapeutic benefits. Clinical trials with tumor-suppressor genes, especially the p53 gene, have demonstrated that the treatment is well tolerated, and; favorable clinical responses, including a pathologically complete responses, have been observed in a subset of patients with advanced disease or with cancers resistant to conventional therapy. Yet, current gene replacement approaches in cancer gene therapy must be improved if they are to have a broader clinical impact. Efficient systemic gene delivery systems will be required ultimately for treatment of metastatic disease. In this review, we have recently summarized achievements in tumor-suppressor gene therapy with a focus on the p53 gene.

  8. Horizontal gene transfer in choanoflagellates. (United States)

    Tucker, Richard P


    Horizontal gene transfer (HGT), also known as lateral gene transfer, results in the rapid acquisition of genes from another organism. HGT has long been known to be a driving force in speciation in prokaryotes, and there is evidence for HGT from symbiotic and infectious bacteria to metazoans, as well as from protists to bacteria. Recently, it has become clear that as many as a 1,000 genes in the genome of the choanoflagellate Monosiga brevicollis may have been acquired by HGT. Interestingly, these genes reportedly come from algae, bacteria, and other choanoflagellate prey. Some of these genes appear to have allowed an ancestral choanoflagellate to exploit nutrient-poor environments and were not passed on to metazoan descendents. However, some of these genes are also found in animal genomes, suggesting that HGT into a common ancestor of choanozoans and animals may have contributed to metazoan evolution. Copyright © 2012 Wiley Periodicals, Inc.

  9. Gene finding in novel genomes

    Directory of Open Access Journals (Sweden)

    Korf Ian


    Full Text Available Abstract Background Computational gene prediction continues to be an important problem, especially for genomes with little experimental data. Results I introduce the SNAP gene finder which has been designed to be easily adaptable to a variety of genomes. In novel genomes without an appropriate gene finder, I demonstrate that employing a foreign gene finder can produce highly inaccurate results, and that the most compatible parameters may not come from the nearest phylogenetic neighbor. I find that foreign gene finders are more usefully employed to bootstrap parameter estimation and that the resulting parameters can be highly accurate. Conclusion Since gene prediction is sensitive to species-specific parameters, every genome needs a dedicated gene finder.

  10. Progress in gene targeting and gene therapy for retinitis pigmentosa

    Energy Technology Data Exchange (ETDEWEB)

    Farrar, G.J.; Humphries, M.M.; Erven, A. [Trinity College, Dublin (Ireland)] [and others


    Previously, we localized disease genes involved in retinitis pigmentosa (RP), an inherited retinal degeneration, close to the rhodopsin and peripherin genes on 3q and 6p. Subsequently, we and others identified mutations in these genes in RP patients. Currently animal models for human retinopathies are being generated using gene targeting by homologous recombination in embryonic stem (ES) cells. Genomic clones for retinal genes including rhodopsin and peripherin have been obtained from a phage library carrying mouse DNA isogenic with the ES cell line (CC1.2). The peripherin clone has been sequenced to establish the genomic structure of the mouse gene. Targeting vectors for rhodopsin and peripherin including a neomycin cassette for positive selection and thymidine kinase genes enabling selection against random intergrants are under construction. Progress in vector construction will be presented. Simultaneously we are developing systems for delivery of gene therapies to retinal tissues utilizing replication-deficient adenovirus (Ad5). Efficacy of infection subsequent to various methods of intraocular injection and with varying viral titers is being assayed using an adenovirus construct containing a CMV promoter LacZ fusion as reporter and the range of tissues infected and the level of duration of LacZ expression monitored. Viral constructs with the LacZ reporter gene under the control of retinal specific promoters such as rhodopsin and IRBP cloned into pXCJL.1 are under construction. An update on developments in photoreceptor cell-directed expression of virally delivered genes will be presented.

  11. From gene expression to gene regulatory networks in Arabidopsis thaliana. (United States)

    Needham, Chris J; Manfield, Iain W; Bulpitt, Andrew J; Gilmartin, Philip M; Westhead, David R


    The elucidation of networks from a compendium of gene expression data is one of the goals of systems biology and can be a valuable source of new hypotheses for experimental researchers. For Arabidopsis, there exist several thousand microarrays which form a valuable resource from which to learn. A novel Bayesian network-based algorithm to infer gene regulatory networks from gene expression data is introduced and applied to learn parts of the transcriptomic network in Arabidopsis thaliana from a large number (thousands) of separate microarray experiments. Starting from an initial set of genes of interest, a network is grown by iterative addition to the model of the gene, from another defined set of genes, which gives the 'best' learned network structure. The gene set for iterative growth can be as large as the entire genome. A number of networks are inferred and analysed; these show (i) an agreement with the current literature on the circadian clock network, (ii) the ability to model other networks, and (iii) that the learned network hypotheses can suggest new roles for poorly characterized genes, through addition of relevant genes from an unconstrained list of over 15,000 possible genes. To demonstrate the latter point, the method is used to suggest that particular GATA transcription factors are regulators of photosynthetic genes. Additionally, the performance in recovering a known network from different amounts of synthetically generated data is evaluated. Our results show that plausible regulatory networks can be learned from such gene expression data alone. This work demonstrates that network hypotheses can be generated from existing gene expression data for use by experimental biologists.

  12. Gene circuit analysis of the terminal gap gene huckebein.

    Directory of Open Access Journals (Sweden)

    Maksat Ashyraliyev


    Full Text Available The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network.

  13. The Caenorhabditis chemoreceptor gene families

    Directory of Open Access Journals (Sweden)

    Robertson Hugh M


    Full Text Available Abstract Background Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Results Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Conclusion Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.


    DEFF Research Database (Denmark)


    The present invention relates to an isolated polynucleotide encoding at least a part of calmodulin and an isolated polypeptide comprising at least a part of a calmodulin protein, wherein the polynucleotide and the polypeptide comprise at least one mutation associated with a cardiac disorder...... the binding of calmodulin to ryanodine receptor 2 and use of such compound in a treatment of an individual having a cardiac disorder. The invention further provides a kit that can be used to detect specific mutations in calmodulin encoding genes....

  15. Gene expression analysis identifies global gene dosage sensitivity in cancer

    DEFF Research Database (Denmark)

    Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata


    Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gene...... expression. We reanalyzed 77,840 expression profiles and observed a limited set of 'transcriptional components' that describe well-known biology, explain the vast majority of variation in gene expression and enable us to predict the biological function of genes. On correcting expression profiles...... for these components, we observed that the residual expression levels (in 'functional genomic mRNA' profiling) correlated strongly with copy number. DNA copy number correlated positively with expression levels for 99% of all abundantly expressed human genes, indicating global gene dosage sensitivity. By applying...

  16. The infinitely many genes model with horizontal gene transfer


    Baumdicker, Franz; Pfaffelhuber, Peter


    The genome of bacterial species is much more flexible than that of eukaryotes. Moreover, the distributed genome hypothesis for bacteria states that the total number of genes present in a bacterial population is greater than the genome of every single individual. The pangenome, i.e. the set of all genes of a bacterial species (or a sample), comprises the core genes which are present in all living individuals, and accessory genes, which are carried only by some individuals. In order to use acce...

  17. Are TMEM genes potential candidate genes for panic disorder?

    DEFF Research Database (Denmark)

    NO, Gregersen; Buttenschøn, Henriette Nørmølle; Hedemand, Anne


    We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12, a previou......We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12...

  18. Gene therapy for psychiatric disorders. (United States)

    Gelfand, Yaroslav; Kaplitt, Michael G


    Gene therapy has become of increasing interest in clinical neurosurgery with the completion of numerous clinical trials for Parkinson disease, Alzheimer disease, and pediatric genetic disorders. With improved understanding of the dysfunctional circuitry mediating various psychiatric disorders, deep brain stimulation for refractory psychiatric diseases is being increasingly explored in human patients. These factors are likely to facilitate development of gene therapy for psychiatric diseases. Because delivery of gene therapy agents would require the same surgical techniques currently being employed for deep brain stimulation, neurosurgeons are likely to lead the development of this field, as has occurred in other areas of clinical gene therapy for neurologic disorders. We review the current state of gene therapy for psychiatric disorders and focus specifically on particular areas of promising research that may translate into human trials for depression, drug addiction, obsessive-compulsive disorder, and schizophrenia. Issues that are relatively unique to psychiatric gene therapy are also discussed. Copyright © 2013. Published by Elsevier Inc.

  19. Gene set analysis for GWAS

    DEFF Research Database (Denmark)

    Debrabant, Birgit; Soerensen, Mette


    Abstract We discuss the use of modified Kolmogorov-Smirnov (KS) statistics in the context of gene set analysis and review corresponding null and alternative hypotheses. Especially, we show that, when enhancing the impact of highly significant genes in the calculation of the test statistic...... parameter and the genesis and distribution of the gene-level statistics, and illustrate the effects of differential weighting in a real-life example....

  20. A genetic ensemble approach for gene-gene interaction identification

    Directory of Open Access Journals (Sweden)

    Ho Joshua WK


    Full Text Available Abstract Background It has now become clear that gene-gene interactions and gene-environment interactions are ubiquitous and fundamental mechanisms for the development of complex diseases. Though a considerable effort has been put into developing statistical models and algorithmic strategies for identifying such interactions, the accurate identification of those genetic interactions has been proven to be very challenging. Methods In this paper, we propose a new approach for identifying such gene-gene and gene-environment interactions underlying complex diseases. This is a hybrid algorithm and it combines genetic algorithm (GA and an ensemble of classifiers (called genetic ensemble. Using this approach, the original problem of SNP interaction identification is converted into a data mining problem of combinatorial feature selection. By collecting various single nucleotide polymorphisms (SNP subsets as well as environmental factors generated in multiple GA runs, patterns of gene-gene and gene-environment interactions can be extracted using a simple combinatorial ranking method. Also considered in this study is the idea of combining identification results obtained from multiple algorithms. A novel formula based on pairwise double fault is designed to quantify the degree of complementarity. Conclusions Our simulation study demonstrates that the proposed genetic ensemble algorithm has comparable identification power to Multifactor Dimensionality Reduction (MDR and is slightly better than Polymorphism Interaction Analysis (PIA, which are the two most popular methods for gene-gene interaction identification. More importantly, the identification results generated by using our genetic ensemble algorithm are highly complementary to those obtained by PIA and MDR. Experimental results from our simulation studies and real world data application also confirm the effectiveness of the proposed genetic ensemble algorithm, as well as the potential benefits of

  1. Gene therapy for hemophilia (United States)

    Rogers, Geoffrey L.; Herzog, Roland W.


    Hemophilia is an X-linked inherited bleeding disorder consisting of two classifications, hemophilia A and hemophilia B, depending on the underlying mutation. Although the disease is currently treatable with intravenous delivery of replacement recombinant clotting factor, this approach represents a significant cost both monetarily and in terms of quality of life. Gene therapy is an attractive alternative approach to the treatment of hemophilia that would ideally provide life-long correction of clotting activity with a single injection. In this review, we will discuss the multitude of approaches that have been explored for the treatment of both hemophilia A and B, including both in vivo and ex vivo approaches with viral and nonviral delivery vectors. PMID:25553466

  2. Introduction: Cancer Gene Networks. (United States)

    Clarke, Robert


    Constructing, evaluating, and interpreting gene networks generally sits within the broader field of systems biology, which continues to emerge rapidly, particular with respect to its application to understanding the complexity of signaling in the context of cancer biology. For the purposes of this volume, we take a broad definition of systems biology. Considering an organism or disease within an organism as a system, systems biology is the study of the integrated and coordinated interactions of the network(s) of genes, their variants both natural and mutated (e.g., polymorphisms, rearrangements, alternate splicing, mutations), their proteins and isoforms, and the organic and inorganic molecules with which they interact, to execute the biochemical reactions (e.g., as enzymes, substrates, products) that reflect the function of that system. Central to systems biology, and perhaps the only approach that can effectively manage the complexity of such systems, is the building of quantitative multiscale predictive models. The predictions of the models can vary substantially depending on the nature of the model and its inputoutput relationships. For example, a model may predict the outcome of a specific molecular reaction(s), a cellular phenotype (e.g., alive, dead, growth arrest, proliferation, and motility), a change in the respective prevalence of cell or subpopulations, a patient or patient subgroup outcome(s). Such models necessarily require computers. Computational modeling can be thought of as using machine learning and related tools to integrate the very high dimensional data generated from modern, high throughput omics technologies including genomics (next generation sequencing), transcriptomics (gene expression microarrays; RNAseq), metabolomics and proteomics (ultra high performance liquid chromatography, mass spectrometry), and "subomic" technologies to study the kinome, methylome, and others. Mathematical modeling can be thought of as the use of ordinary

  3. Pompe disease gene therapy (United States)

    Byrne, Barry J.; Falk, Darin J.; Pacak, Christina A.; Nayak, Sushrusha; Herzog, Roland W.; Elder, Melissa E.; Collins, Shelley W.; Conlon, Thomas J.; Clement, Nathalie; Cleaver, Brian D.; Cloutier, Denise A.; Porvasnik, Stacy L.; Islam, Saleem; Elmallah, Mai K.; Martin, Anatole; Smith, Barbara K.; Fuller, David D.; Lawson, Lee Ann; Mah, Cathryn S.


    Pompe disease is an autosomal recessive metabolic myopathy caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase and results in cellular lysosomal and cytoplasmic glycogen accumulation. A wide spectrum of disease exists from hypotonia and severe cardiac hypertrophy in the first few months of life due to severe mutations to a milder form with the onset of symptoms in adulthood. In either condition, the involvement of several systems leads to progressive weakness and disability. In early-onset severe cases, the natural history is characteristically cardiorespiratory failure and death in the first year of life. Since the advent of enzyme replacement therapy (ERT), the clinical outcomes have improved. However, it has become apparent that a new natural history is being defined in which some patients have substantial improvement following ERT, while others develop chronic disability reminiscent of the late-onset disease. In order to improve on the current clinical outcomes in Pompe patients with diminished clinical response to ERT, we sought to address the cause and potential for the treatment of disease manifestations which are not amenable to ERT. In this review, we will focus on the preclinical studies that are relevant to the development of a gene therapy strategy for Pompe disease, and have led to the first clinical trial of recombinant adeno-associated virus-mediated gene-based therapy for Pompe disease. We will cover the preliminary laboratory studies and rationale for a clinical trial, which is based on the treatment of the high rate of respiratory failure in the early-onset patients receiving ERT. PMID:21518733

  4. Gene therapy for meningioma : improved gene delivery with targeted adenoviruses

    NARCIS (Netherlands)

    Dirven, CMF; Grill, J; Lamfers, MLM; Van der Valk, P; Leonhart, AM; Van Beusechem, VW; Haisma, HJ; Pinedo, HM; Curiel, DT; Vandertop, WP; Gerritsen, WR

    Object. Due to their surgical inaccessibility or aggressive behavior, some meningiomas cannot be cured with current treatment strategies. Gene therapy is an emerging strategy for the treatment of brain tumors, which the authors investigated to determine whether adenoviruses could be used for gene

  5. Gene-gene Interaction Analyses for Atrial Fibrillation

    NARCIS (Netherlands)

    H. Lin (Honghuang); M. Mueller-Nurasyid; A.V. Smith (Albert Vernon); D.E. Arking (Dan); J. Barnard (John); T.M. Bartz (Traci M.); K.L. Lunetta (Kathryn); K. Lohman (Kurt); M.E. Kleber (Marcus); S.A. Lubitz (Steven); Geelhoed, B. (Bastiaan); S. Trompet (Stella); M.N. Niemeijer (Maartje); T. Kacprowski (Tim); D.I. Chasman (Daniel); Klarin, D. (Derek); M.F. Sinner (Moritz); M. Waldenberger (Melanie); T. Meitinger (Thomas); T.B. Harris (Tamara); L.J. Launer (Lenore); E.Z. Soliman (Elsayed Z.); L. Chen (Lin); J.D. Smith (Jonathan); D.R. van Wagoner (David); Rotter, J.I. (Jerome I.); B.M. Psaty (Bruce); Xie, Z. (Zhijun); A.E. Hendricks (Audrey E.); Ding, J. (Jingzhong); G.E. Delgado (Graciela E.); N. Verweij (Niek); P. van der Harst (Pim); P.W. MacFarlane (Peter); I. Ford (Ian); A. Hofman (Albert); A.G. Uitterlinden (André); J. Heeringa (Jan); O.H. Franco (Oscar); J.A. Kors (Jan); Weiss, S. (Stefan); H. Völzke (Henry); L.M. Rose (Lynda); Natarajan, P. (Pradeep); S. Kathiresan (Sekar); S. Kääb (Stefan); V. Gudnason (Vilmundur); A. Alonso (Alvaro); M.K. Chung (Mina); S.R. Heckbert (Susan); E.J. Benjamin (Emelia); Y. Liu (Yongmei); W. März (Winfried); S.A. Rienstra; J.W. Jukema (Jan Wouter); B.H.Ch. Stricker (Bruno); M. Dörr (Marcus); C.M. Albert (Christine); P.T. Ellinor (Patrick)


    textabstractAtrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility.

  6. Gene-gene Interaction Analyses for Atrial Fibrillation

    NARCIS (Netherlands)

    Lin, Honghuang; Mueller-Nurasyid, Martina; Smith, Albert V.; Arking, Dan E.; Barnard, John; Bartz, Traci M.; Lunetta, Kathryn L.; Lohman, Kurt; Kleber, Marcus E.; Lubitz, Steven A.; Geelhoed, Bastiaan; Trompet, Stella; Niemeijer, Maartje N.; Kacprowski, Tim; Chasman, Daniel I.; Klarin, Derek; Sinner, Moritz F.; Waldenberger, Melanie; Meitinger, Thomas; Harris, Tamara B.; Launer, Lenore J.; Soliman, Elsayed Z.; Chen, Lin Y.; Smith, Jonathan D.; Van Wagoner, David R.; Rotter, Jerome I.; Psaty, Bruce M.; Xie, Zhijun; Hendricks, Audrey E.; Ding, Jingzhong; Delgado, Graciela E.; Verweij, Niek; van der Harst, Pim; Macfarlane, Peter W.; Ford, Ian; Hofman, Albert; Uitterlinden, Andre; Heeringa, Jan; Franco, Oscar H.; Kors, Jan A.; Weiss, Stefan; Volzke, Henry; Rose, Lynda M.; Natarajan, Pradeep; Kathiresan, Sekar; Kaab, Stefan; Gudnason, Vilmundur; Alonso, Alvaro; Chung, Mina K.; Heckbert, Susan R.; Benjamin, Emelia J.; Liu, Yongmei; Marz, Winfried; Rienstra, Michiel; Jukema, J. Wouter; Stricker, Bruno H.; Dorr, Marcus; Albert, Christine M.; Ellinor, Patrick T.


    Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed

  7. Classifying genes to the correct Gene Ontology Slim term in Saccharomyces cerevisiae using neighbouring genes with classification learning

    Directory of Open Access Journals (Sweden)

    Tsatsoulis Costas


    Full Text Available Abstract Background There is increasing evidence that gene location and surrounding genes influence the functionality of genes in the eukaryotic genome. Knowing the Gene Ontology Slim terms associated with a gene gives us insight into a gene's functionality by informing us how its gene product behaves in a cellular context using three different ontologies: molecular function, biological process, and cellular component. In this study, we analyzed if we could classify a gene in Saccharomyces cerevisiae to its correct Gene Ontology Slim term using information about its location in the genome and information from its nearest-neighbouring genes using classification learning. Results We performed experiments to establish that the MultiBoostAB algorithm using the J48 classifier could correctly classify Gene Ontology Slim terms of a gene given information regarding the gene's location and information from its nearest-neighbouring genes for training. Different neighbourhood sizes were examined to determine how many nearest neighbours should be included around each gene to provide better classification rules. Our results show that by just incorporating neighbour information from each gene's two-nearest neighbours, the percentage of correctly classified genes to their correct Gene Ontology Slim term for each ontology reaches over 80% with high accuracy (reflected in F-measures over 0.80 of the classification rules produced. Conclusions We confirmed that in classifying genes to their correct Gene Ontology Slim term, the inclusion of neighbour information from those genes is beneficial. Knowing the location of a gene and the Gene Ontology Slim information from neighbouring genes gives us insight into that gene's functionality. This benefit is seen by just including information from a gene's two-nearest neighbouring genes.

  8. Electro-acupuncture-mediated gene transfer. (United States)

    Zhang, J; Qin, Y; Fu, A; Tang, J; Chen, G; Cai, D; Han, J


    Gene transfer is one of the key techniques in gene therapy application. Unfortunately, it seems that by now, there still exists no approach with simplicity, easiness, efficiency and safety. A novel method for gene delivery, electro-acupuncture needle-mediated gene transfer which combined the Chinese traditional acupuncture with modem gene introduction, was developed. With acupuncture needle carrying exogenous gene into muscle after direct electronic stimuli, efficient gene delivery was achieved.

  9. Determining Semantically Related Significant Genes. (United States)

    Taha, Kamal


    GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement.

  10. Uncovering trends in gene naming


    Seringhaus, Michael R.; Cayting, Philip D; Gerstein, Mark B.


    We take stock of current genetic nomenclature and attempt to organize strange and notable gene names. We categorize, for instance, those that involve a naming system transferred from another context (for example, Pavlov’s dogs). We hope this analysis provides clues to better steer gene naming in the future.

  11. Uncovering trends in gene naming. (United States)

    Seringhaus, Michael R; Cayting, Philip D; Gerstein, Mark B


    We take stock of current genetic nomenclature and attempt to organize strange and notable gene names. We categorize, for instance, those that involve a naming system transferred from another context (for example, Pavlov's dogs). We hope this analysis provides clues to better steer gene naming in the future.

  12. Gene Synthesis with HG Khorana

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 17; Issue 12. Gene Synthesis with H G Khorana. Marvin H Caruthers. General Article Volume 17 Issue 12 December 2012 pp ... Keywords. Chemical synthesis of genes for yeast alanine tRNA and E. coli supressor tRNA; Khorana's philosophy on science.

  13. Susceptibility Genes in Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ban


    Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.

  14. On meme--gene coevolution. (United States)

    Bull, L; Holland, O; Blackmore, S


    In this article we examine the effects of the emergence of a new replicator, memes, on the evolution of a pre-existing replicator, genes. Using a version of the NKCS model we examine the effects of increasing the rate of meme evolution in relation to the rate of gene evolution, for various degrees of interdependence between the two replicators. That is, the effects of memes' (suggested) more rapid rate of evolution in comparison to that of genes is investigated using a tunable model of coevolution. It is found that, for almost any degree of interdependence between the two replicators, as the rate of meme evolution increases, a phase transition-like dynamic occurs under which memes have a significantly detrimental effect on the evolution of genes, quickly resulting in the cessation of effective gene evolution. Conversely, the memes experience a sharp increase in benefit from increasing their rate of evolution. We then examine the effects of enabling genes to reduce the percentage of gene-detrimental evolutionary steps taken by memes. Here a critical region emerges as the comparative rate of meme evolution increases, such that if genes cannot effectively select memes a high percentage of the time, they suffer from meme evolution as if they had almost no selective capability.

  15. Vemurafenib-resistance via de novo RBM genes mutations and chromosome 5 aberrations is overcome by combined therapy with palbociclib in thyroid carcinoma with BRAF(V600E). (United States)

    Antonello, Zeus A; Hsu, Nancy; Bhasin, Manoj; Roti, Giovanni; Joshi, Mukta; Van Hummelen, Paul; Ye, Emily; Lo, Agnes S; Karumanchi, S Ananth; Bryke, Christine R; Nucera, Carmelo


    Papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor. BRAF(V600E) represents the PTC hallmark and is targeted with selective inhibitors (e.g. vemurafenib). Although there have been promising results in clinical trials using these inhibitors, most patients develop resistance and progress. Tumor clonal diversity is proposed as one mechanism underlying drug resistance. Here we have investigated mechanisms of primary and secondary resistance to vemurafenib in BRAF(WT/V600E)-positive PTC patient-derived cells with P16(-/-) (CDKN2A(-/-)). Following treatment with vemurafenib, we expanded a sub-population of cells with primary resistance and characterized them genetically and cytogenetically. We have used exome sequencing, metaphase chromosome analysis, FISH and oligonucleotide SNP-microarray assays to assess clonal evolution of vemurafenib-resistant cells. Furthermore, we have validated our findings by networks and pathways analyses using PTC clinical samples. Vemurafenib-resistant cells grow similarly to naïve cells but are refractory to apoptosis upon treatment with vemurafenib, and accumulate in G2-M phase. We find that vemurafenib-resistant cells show amplification of chromosome 5 and de novo mutations in the RBM (RNA-binding motifs) genes family (i.e. RBMX, RBM10). RBMX knockdown in naïve-cells contributes to tetraploidization, including expansion of clones with chromosome 5 aberrations (e.g. isochromosome 5p). RBMX elicits gene regulatory networks with chromosome 5q cancer-associated genes and pathways for G2-M and DNA damage-response checkpoint regulation in BRAF(WT/V600E)-PTC. Importantly, combined therapy with vemurafenib plus palbociclib (inhibitor of CDK4/6, mimicking P16 functions) synergistically induces stronger apoptosis than single agents in resistant-cells and in anaplastic thyroid tumor cells harboring the heterozygous BRAF(WT/V600E) mutation. Critically, our findings suggest for the first time that targeting BRAF(WT/V600E) and CDK4

  16. Homeobox gene expression in Brachiopoda

    DEFF Research Database (Denmark)

    Altenburger, Andreas; Martinez, Pedro; Wanninger, Andreas


    The molecular control that underlies brachiopod ontogeny is largely unknown. In order to contribute to this issue we analyzed the expression pattern of two homeobox containing genes, Not and Cdx, during development of the rhynchonelliform (i.e., articulate) brachiopod Terebratalia transversa....... Not is a homeobox containing gene that regulates the formation of the notochord in chordates, while Cdx (caudal) is a ParaHox gene involved in the formation of posterior tissues of various animal phyla. The T. transversa homolog, TtrNot, is expressed in the ectoderm from the beginning of gastrulation until...... formation. TtrNot expression is absent in unfertilized eggs, in embryos prior to gastrulation, and in settled individuals during and after metamorphosis. Comparison with the expression patterns of Not genes in other metazoan phyla suggests an ancestral role for this gene in gastrulation and germ layer...

  17. CNS Genes Implicated in Relapse

    Directory of Open Access Journals (Sweden)

    Willard M. Freeman


    Full Text Available Drug abuse is a condition that impacts not only the individual drug user, but society as a whole. Although prevention of initial drug use is the most effective way to prevent addiction, avoiding relapse is a crucial component of drug addiction recovery. Recent studies suggest that there is a set of genes whose expression is robustly and stably altered following drug use and ensuing abstinence. Such stable changes in gene expression correlate with ultrastructural changes in brain as well as alterations in behavior. As persistent molecular changes, these genes may provide targets for the development of therapeutics. Developing a list of well-characterized candidate genes and examining the effect of manipulating these genes will contribute to the ultimate goal of developing effective treatments to prevent relapse to drug use.

  18. Gene Discovery Methods from Large-Scale Gene Expression Data (United States)

    Shimizu, Akifumi; Yano, Kentaro


    Microarrays provide genome-wide gene expression changes. In current analyses, the majority of genes on the array are frequently eliminated for further analysis just in order for computational effort to be affordable. This strategy risks failure to discover whole sets of genes related to a quantitative trait of interest, which is generally controlled by several loci that might be eliminated in current approaches. Here, we describe a high-throughput gene discovery method based on correspondence analysis with a new index for expression ratios [arctan (1/ratio)] and three artificial marker genes. This method allows us to quickly analyze the whole microarray dataset without elimination and discover up/down-regulated genes related to a trait of interest. We employed an example dataset to show the theoretical advantage of this method. We then used the method to identify 88 cancer-related genes from a published microarray data from patients with breast cancer. This method can be easily performed and the result is also visible in three-dimensional viewing software that we have developed. Our method is useful for revaluating the wealth of microarray data available from web-sites.

  19. Gene recognition by combination of several gene-finding programs. (United States)

    Murakami, K; Takagi, T


    A number of programs have been developed to predict the eukaryotic gene structures in DNA sequences. However, gene finding is still a challenging problem. We have explored the effectiveness when the results of several gene-finding programs were re-analyzed and combined. We studied several methods with four programs (FEXH, GeneParser3, GEN-SCAN and GRAIL2). By HIGHEST-policy combination method or BOUNDARY method, approximate correlation (AC) improved by 3-5% in comparison with the best single gene-finding program. From another viewpoint, OR-based combination of the four programs is the most reliable to know whether a candidate exon overlaps with the real exon or not, although it is less sensitive than GENSCAN for exon-intron boundaries. Our methods can easily be extended to combine other programs. We have developed a server program (Shirokane System) and a client program (GeneScope) to use the methods. GeneScope is available through a WWW site ( (katsu,takagi)

  20. Reference gene screening for analyzing gene expression across goat tissue. (United States)

    Zhang, Yu; Zhang, Xiao-Dong; Liu, Xing; Li, Yun-Sheng; Ding, Jian-Ping; Zhang, Xiao-Rong; Zhang, Yun-Hai


    Real-time quantitative PCR (qRT-PCR) is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2) in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken.

  1. Reference Gene Screening for Analyzing Gene Expression Across Goat Tissue

    Directory of Open Access Journals (Sweden)

    Yu Zhang


    Full Text Available Real-time quantitative PCR (qRT-PCR is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2 in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken.

  2. Phylogenetic analysis of gene expression. (United States)

    Dunn, Casey W; Luo, Xi; Wu, Zhijin


    Phylogenetic analyses of gene expression have great potential for addressing a wide range of questions. These analyses will, for example, identify genes that have evolutionary shifts in expression that are correlated with evolutionary changes in morphological, physiological, and developmental characters of interest. This will provide entirely new opportunities to identify genes related to particular phenotypes. There are, however, 3 key challenges that must be addressed for such studies to realize their potential. First, data on gene expression must be measured from multiple species, some of which may be field-collected, and parameterized in such a way that they can be compared across species. Second, it will be necessary to develop comparative phylogenetic methods suitable for large multidimensional datasets. In most phylogenetic comparative studies to date, the number n of independent observations (independent contrasts) has been greater than the number p of variables (characters). The behavior of comparative methods for these classic problems is now well understood under a wide variety of conditions. In studies of gene expression, and in studies based on other high-throughput tools, the number n of samples is dwarfed by the number p of variables. The estimated covariance matrices will be singular, complicating their analysis and interpretation, and prone to spurious results. Third, new approaches are needed to investigate the expression of the many genes whose phylogenies are not congruent with species phylogenies due to gene loss, gene duplication, and incomplete lineage sorting. Here we outline general considerations of project design for phylogenetic analyses of gene expression and suggest solutions to these three categories of challenges. These topics are relevant to high-throughput phenotypic data well beyond gene expression.

  3. Gene Prediction Using Multinomial Probit Regression with Bayesian Gene Selection (United States)

    Zhou, Xiaobo; Wang, Xiaodong; Dougherty, Edward R.


    A critical issue for the construction of genetic regulatory networks is the identification of network topology from data. In the context of deterministic and probabilistic Boolean networks, as well as their extension to multilevel quantization, this issue is related to the more general problem of expression prediction in which we want to find small subsets of genes to be used as predictors of target genes. Given some maximum number of predictors to be used, a full search of all possible predictor sets is combinatorially prohibitive except for small predictors sets, and even then, may require supercomputing. Hence, suboptimal approaches to finding predictor sets and network topologies are desirable. This paper considers Bayesian variable selection for prediction using a multinomial probit regression model with data augmentation to turn the multinomial problem into a sequence of smoothing problems. There are multiple regression equations and we want to select the same strongest genes for all regression equations to constitute a target predictor set or, in the context of a genetic network, the dependency set for the target. The probit regressor is approximated as a linear combination of the genes and a Gibbs sampler is employed to find the strongest genes. Numerical techniques to speed up the computation are discussed. After finding the strongest genes, we predict the target gene based on the strongest genes, with the coefficient of determination being used to measure predictor accuracy. Using malignant melanoma microarray data, we compare two predictor models, the estimated probit regressors themselves and the optimal full-logic predictor based on the selected strongest genes, and we compare these to optimal prediction without feature selection.

  4. Gene Prediction Using Multinomial Probit Regression with Bayesian Gene Selection

    Directory of Open Access Journals (Sweden)

    Wang Xiaodong


    Full Text Available A critical issue for the construction of genetic regulatory networks is the identification of network topology from data. In the context of deterministic and probabilistic Boolean networks, as well as their extension to multilevel quantization, this issue is related to the more general problem of expression prediction in which we want to find small subsets of genes to be used as predictors of target genes. Given some maximum number of predictors to be used, a full search of all possible predictor sets is combinatorially prohibitive except for small predictors sets, and even then, may require supercomputing. Hence, suboptimal approaches to finding predictor sets and network topologies are desirable. This paper considers Bayesian variable selection for prediction using a multinomial probit regression model with data augmentation to turn the multinomial problem into a sequence of smoothing problems. There are multiple regression equations and we want to select the same strongest genes for all regression equations to constitute a target predictor set or, in the context of a genetic network, the dependency set for the target. The probit regressor is approximated as a linear combination of the genes and a Gibbs sampler is employed to find the strongest genes. Numerical techniques to speed up the computation are discussed. After finding the strongest genes, we predict the target gene based on the strongest genes, with the coefficient of determination being used to measure predictor accuracy. Using malignant melanoma microarray data, we compare two predictor models, the estimated probit regressors themselves and the optimal full-logic predictor based on the selected strongest genes, and we compare these to optimal prediction without feature selection.

  5. Therapeutic genes for anti-HIV/AIDS gene therapy. (United States)

    Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca


    The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

  6. Evidence based selection of housekeeping genes

    NARCIS (Netherlands)

    de Jonge, Hendrik J. M.; Fehrmann, Rudolf S. N.; de Bont, Eveline S. J. M.; Hofstra, Robert M. W.; Gerbens, Frans; Kamps, Willem A.; de Vries, Elisabeth G. E.; van der Zee, Ate G. J.; te Meerman, Gerard J.; ter Elst, Arja


    For accurate and reliable gene expression analysis, normalization of gene expression data against housekeeping genes (reference or internal control genes) is required. It is known that commonly used housekeeping genes (e. g. ACTB, GAPDH, HPRT1, and B2M) vary considerably under different experimental

  7. Human Lacrimal Gland Gene Expression.

    Directory of Open Access Journals (Sweden)

    Vinay Kumar Aakalu

    Full Text Available The study of human lacrimal gland biology and development is limited. Lacrimal gland tissue is damaged or poorly functional in a number of disease states including dry eye disease. Development of cell based therapies for lacrimal gland diseases requires a better understanding of the gene expression and signaling pathways in lacrimal gland. Differential gene expression analysis between lacrimal gland and other embryologically similar tissues may be helpful in furthering our understanding of lacrimal gland development.We performed global gene expression analysis of human lacrimal gland tissue using Affymetrix ® gene expression arrays. Primary data from our laboratory was compared with datasets available in the NLM GEO database for other surface ectodermal tissues including salivary gland, skin, conjunctiva and corneal epithelium.The analysis revealed statistically significant difference in the gene expression of lacrimal gland tissue compared to other ectodermal tissues. The lacrimal gland specific, cell surface secretory protein encoding genes and critical signaling pathways which distinguish lacrimal gland from other ectodermal tissues are described.Differential gene expression in human lacrimal gland compared with other ectodermal tissue types revealed interesting patterns which may serve as the basis for future studies in directed differentiation among other areas.

  8. GENES IN SPORT AND DOPING (United States)

    Kaliszewski, P.; Majorczyk, E.; Zembroń-Łacny, A.


    Genes control biological processes such as muscle production of energy, mitochondria biogenesis, bone formation, erythropoiesis, angiogenesis, vasodilation, neurogenesis, etc. DNA profiling for athletes reveals genetic variations that may be associated with endurance ability, muscle performance and power exercise, tendon susceptibility to injuries and psychological aptitude. Already, over 200 genes relating to physical performance have been identified by several research groups. Athletes’ genotyping is developing as a tool for the formulation of personalized training and nutritional programmes to optimize sport training as well as for the prediction of exercise-related injuries. On the other hand, development of molecular technology and gene therapy creates a risk of non-therapeutic use of cells, genes and genetic elements to improve athletic performance. Therefore, the World Anti-Doping Agency decided to include prohibition of gene doping within their World Anti-Doping Code in 2003. In this review article, we will provide a current overview of genes for use in athletes’ genotyping and gene doping possibilities, including their development and detection techniques. PMID:24744482


    Directory of Open Access Journals (Sweden)

    Andrzej Pokrywka


    Full Text Available Genes control biological processes such as muscle production of energy, mitochondria biogenesis, bone formation erythropoiesis, angiogenesis, vasodilation, neurogenesis, etc. DNA profiling for athletes reveals genetic variations that may be associated with endurance ability, muscle performance and power exercise, tendon susceptibility to injuries and psychological aptitude. Already, over 200 genes relating to physical performance have been identified by several research groups. Athletes’ genotyping is developing as a tool for the formulation of personalized training and nutritional programmes to optimize sport training as well as for the prediction of exercise-related injuries. On the other hand, development of molecular technology and gene therapy creates a risk of non-therapeutic use of cells, genes and genetic elements to improve athletic performance. Therefore, the World Anti-Doping Agency decided to include prohibition of gene doping within their World Anti-Doping Code in 2003. In this review article, we will provide a current overview of genes for use in athletes’ genotyping and gene doping possibilities, including their development and detection techniques.

  10. Gene expression profiles in skeletal muscle after gene electrotransfer

    DEFF Research Database (Denmark)

    Hojman, Pernille; Zibert, John R; Gissel, Hanne


    BACKGROUND: Gene transfer by electroporation (DNA electrotransfer) to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have...... therefore investigated transcriptional changes through gene expression profile analyses, morphological changes by histological analysis, and physiological changes by force generation measurements. DNA electrotransfer was obtained using a combination of a short high voltage pulse (HV, 1000 V/cm, 100 mus......) followed by a long low voltage pulse (LV, 100 V/cm, 400 ms); a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP) and excised at 4 hours, 48 hours or 3 weeks after treatment. RESULTS: Differentially expressed genes were...

  11. Cloning and selection of reference genes for gene expression ...

    African Journals Online (AJOL)

    Full length mRNA sequences of Ac-β-actin and Ac-gapdh, and partial mRNA sequences of Ac-18SrRNA and Ac-ubiquitin were cloned from pineapple in this study. The four genes were tested as housekeeping genes in three experimental sets. GeNorm and NormFinder analysis revealed that β-actin was the most ...

  12. Gene therapy of cancer by vaccines carrying inserted immunostimulatory genes

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan


    Roč. 53, č. 3 (2007), s. 71-73 ISSN 0015-5500 Grant - others:EU-FP6 NoE Clinigene(XE) 018933; Liga proti rakovině, Praha(CZ) XX Institutional research plan: CEZ:AV0Z50520514 Keywords : gene therapy * immunostimulatory genes * vaccine Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.596, year: 2007

  13. Correction of gene expression data

    DEFF Research Database (Denmark)

    Darbani Shirvanehdeh, Behrooz; Stewart, C. Neal, Jr.; Noeparvar, Shahin


    This report investigates for the first time the potential inter-treatment bias source of cell number for gene expression studies. Cell-number bias can affect gene expression analysis when comparing samples with unequal total cellular RNA content or with different RNA extraction efficiencies....... For maximal reliability of analysis, therefore, comparisons should be performed at the cellular level. This could be accomplished using an appropriate correction method that can detect and remove the inter-treatment bias for cell-number. Based on inter-treatment variations of reference genes, we introduce...

  14. Gene Therapy Approaches to Hemoglobinopathies. (United States)

    Ferrari, Giuliana; Cavazzana, Marina; Mavilio, Fulvio


    Gene therapy for hemoglobinopathies is currently based on transplantation of autologous hematopoietic stem cells genetically modified with a lentiviral vector expressing a globin gene under the control of globin transcriptional regulatory elements. Preclinical and early clinical studies showed the safety and potential efficacy of this therapeutic approach as well as the hurdles still limiting its general application. In addition, for both beta-thalassemia and sickle cell disease, an altered bone marrow microenvironment reduces the efficiency of stem cell harvesting as well as engraftment. These hurdles need be addressed for gene therapy for hemoglobinopathies to become a clinical reality. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Panspermia and horizontal gene transfer (United States)

    Klyce, Brig


    Evidence that extremophiles are hardy and ubiquitous is helping to make panspermia a respectable theory. But even if life on Earth originally came from space, biologists assume that the subsequent evolution of life is still governed by the darwinian paradigm. In this review we show how panspermia could amend darwinism and point to a cosmic source for, not only extremophiles but, all of life. This version of panspermia can be called "strong panspermia." To support this theory we will discuss recent evidence pertaining to horizontal gene transfer, viruses, genes apparently older than the Earthly evolution of the features they encode, and primate-specific genes without identifiable precursors.

  16. Genomics screens for metastasis genes (United States)

    Yan, Jinchun; Huang, Qihong


    Metastasis is responsible for most cancer mortality. The process of metastasis is complex, requiring the coordinated expression and fine regulation of many genes in multiple pathways in both the tumor and host tissues. Identification and characterization of the genetic programs that regulate metastasis is critical to understanding the metastatic process and discovering molecular targets for the prevention and treatment of metastasis. Genomic approaches and functional genomic analyses can systemically discover metastasis genes. In this review, we summarize the genetic tools and methods that have been used to identify and characterize the genes that play critical roles in metastasis. PMID:22684367

  17. American Society of Gene & Cell Therapy (United States)

    ... Chicago Learn More Close The American Society of Gene & Cell Therapy ASGCT is the primary membership organization for scientists, ... Therapeutics Official Journal of the American Society of Gene & Cell Therapy Molecular Therapy is the leading journal for gene ...

  18. Gene Expression Analysis of Breast Cancer Progression

    National Research Council Canada - National Science Library

    Gerald, Wiliam L


    ... to identify genes, gene expression profiles and molecular pathways associated with metastatic BC we have performed genome-wide gene expression analysis of a large number of breast cancer samples...

  19. Novel genes in LDL metabolism

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Tybjærg-Hansen, Anne


    PURPOSE OF REVIEW: To summarize recent findings from genome-wide association studies (GWAS), whole-exome sequencing of patients with familial hypercholesterolemia and 'exome chip' studies pointing to novel genes in LDL metabolism. RECENT FINDINGS: The genetic loci for ATP-binding cassette......-exome sequencing and 'exome chip' studies have additionally suggested several novel genes in LDL metabolism including insulin-induced gene 2, signal transducing adaptor family member 1, lysosomal acid lipase A, patatin-like phospholipase domain-containing protein 5 and transmembrane 6 superfamily member 2. Most...... of these findings still require independent replications and/or functional studies to confirm the exact role in LDL metabolism and the clinical implications for human health. SUMMARY: GWAS, exome sequencing studies, and recently 'exome chip' studies have suggested several novel genes with effects on LDL cholesterol...

  20. Candidate genes in panic disorder

    DEFF Research Database (Denmark)

    Howe, A. S.; Buttenschön, Henriette N; Bani-Fatemi, A.


    The utilization of molecular genetics approaches in examination of panic disorder (PD) has implicated several variants as potential susceptibility factors for panicogenesis. However, the identification of robust PD susceptibility genes has been complicated by phenotypic diversity, underpowered...

  1. Sleep deprivation and gene expression. (United States)

    da Costa Souza, Annie; Ribeiro, Sidarta


    Sleep occurs in a wide range of animal species as a vital process for the maintenance of homeostasis, metabolic restoration, physiological regulation, and adaptive cognitive functions in the central nervous system. Long-term perturbations induced by the lack of sleep are mostly mediated by changes at the level of transcription and translation. This chapter reviews studies in humans, rodents, and flies to address the various ways by which sleep deprivation affects gene expression in the nervous system, with a focus on genes related to neuronal plasticity, brain function, and cognition. However, the effects of sleep deprivation on gene expression and the functional consequences of sleep loss are clearly not restricted to the cognitive domain but may include increased inflammation, expression of stress-related genes, general impairment of protein translation, metabolic imbalance, and thermal deregulation.

  2. Gene Therapy for Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Rachel Denyer


    Full Text Available Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field.

  3. Deregulated genes in sporadic vestibular schwannomas

    DEFF Research Database (Denmark)

    Cayé-Thomasen, Per; Helweg-Larsen, Rehannah Holga Andrea; Stangerup, Sven-Eric


    In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology....

  4. Gene expression based cancer classification


    Sara Tarek; Reda Abd Elwahab; Mahmoud Shoman


    Cancer classification based on molecular level investigation has gained the interest of researches as it provides a systematic, accurate and objective diagnosis for different cancer types. Several recent researches have been studying the problem of cancer classification using data mining methods, machine learning algorithms and statistical methods to reach an efficient analysis for gene expression profiles. Studying the characteristics of thousands of genes simultaneously offered a deep in...

  5. Transgenic Arabidopsis Gene Expression System (United States)

    Ferl, Robert; Paul, Anna-Lisa


    The Transgenic Arabidopsis Gene Expression System (TAGES) investigation is one in a pair of investigations that use the Advanced Biological Research System (ABRS) facility. TAGES uses Arabidopsis thaliana, thale cress, with sensor promoter-reporter gene constructs that render the plants as biomonitors (an organism used to determine the quality of the surrounding environment) of their environment using real-time nondestructive Green Fluorescent Protein (GFP) imagery and traditional postflight analyses.

  6. Gene mutations in hepatocellular adenomas

    DEFF Research Database (Denmark)

    Raft, Marie B; Jørgensen, Ernö N; Vainer, Ben


    is associated with bi-allelic mutations in the TCF1 gene and morphologically has marked steatosis. β-catenin activating HCA has increased activity of the Wnt/β-catenin pathway and is associated with possible malignant transformation. Inflammatory HCA is characterized by an oncogene-induced inflammation due....... This review offers an overview of the reported gene mutations associated with hepatocellular adenomas together with a discussion of the diagnostic and prognostic value....

  7. Rice Multi-Gene Analysis

    Indian Academy of Sciences (India)


    Maps of all the intronic MIR genes analyzed using MPSS database in rice. Click here for a legend that explains the icons and colors in the image below. Click here to jump in the page below to the specific gene. osa-MIR159f osa-MIR399i osa-MIR418 osa-MIR437 osa-MIR439b osa-MIR439j osa-MIR440 osa-MIR442.

  8. Degradable Polymers for Gene Delivery (United States)

    Sunshine, Joel; Bhise, Nupura; Green, Jordan J.


    Degradable polymers were synthesized that self-assemble with DNA to form particles that are effective for gene delivery. Small changes to polymer synthesis conditions, particle formulation conditions, and polymer structure led to significant changes to efficacy in a cell-type dependent manner. Polymers presented here are more effective than Lipofectamine 2000 or polyethylenimine for gene delivery to cancerous fibroblasts or human primary fibroblasts. These materials may be useful for cancer therapeutics and regenerative medicine. PMID:19964958

  9. Cationic Bolaamphiphiles for Gene Delivery (United States)

    Tan, Amelia Li Min; Lim, Alisa Xue Ling; Zhu, Yiting; Yang, Yi Yan; Khan, Majad


    Advances in medical research have shed light on the genetic cause of many human diseases. Gene therapy is a promising approach which can be used to deliver therapeutic genes to treat genetic diseases at its most fundamental level. In general, nonviral vectors are preferred due to reduced risk of immune response, but they are also commonly associated with low transfection efficiency and high cytotoxicity. In contrast to viral vectors, nonviral vectors do not have a natural mechanism to overcome extra- and intracellular barriers when delivering the therapeutic gene into cell. Hence, its design has been increasingly complex to meet challenges faced in targeting of, penetration of and expression in a specific host cell in achieving more satisfactory transfection efficiency. Flexibility in design of the vector is desirable, to enable a careful and controlled manipulation of its properties and functions. This can be met by the use of bolaamphiphile, a special class of lipid. Unlike conventional lipids, bolaamphiphiles can form asymmetric complexes with the therapeutic gene. The advantage of having an asymmetric complex lies in the different purposes served by the interior and exterior of the complex. More effective gene encapsulation within the interior of the complex can be achieved without triggering greater aggregation of serum proteins with the exterior, potentially overcoming one of the great hurdles faced by conventional single-head cationic lipids. In this review, we will look into the physiochemical considerations as well as the biological aspects of a bolaamphiphile-based gene delivery system.

  10. ASPM gene expression in medulloblastoma. (United States)

    Vulcani-Freitas, Tânia M; Saba-Silva, Najsla; Cappellano, Andréa; Cavalheiro, Sérgio; Marie, Sueli K N; Oba-Shinjo, Sueli M; Malheiros, Suzana M F; de Toledo, Sílvia Regina Caminada


    Medulloblastomas are the most common malignant tumors of the central nervous system in childhood. The incidence is about 19-20% between children younger than 16 years old with peak incidence between 4 and 7 years. Despite its sensibility to no specific therapeutic means like chemotherapy and radiotherapy, the treatment is very aggressive and frequently results in regression, growth deficit, and endocrine dysfunction. From this point of view, new treatment approaches are needed such as molecular targeted therapies. Studies in glioblastoma demonstrated that ASPM gene was overexpressed when compared to normal brain and ASPM inhibition by siRNA-mediated inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM gene as a potential molecular target in glioblastoma. The aim of this work was to evaluate ASPM expression in medulloblastoma fragment samples, and to compare the results with the patient clinical features. Analysis of gene expression was performed by quantitative PCR real time using SYBR Green system in tumor samples from 37 children. The t test was used to analyze the gene expression, and Mann-Whitney test was performed to analyze the relationship between gene expressions and clinical characteristics. Kaplan-Meier test evaluated curve survival. All samples overexpressed ASPM gene more than 40-fold. However, we did not find any association between the overexpressed samples and the clinical parameters. ASPM overexpression may modify the ability of stem cells to differentiate during the development of the central nervous system, contributing to the development of medulloblastoma, a tumor of embryonic origin from cerebellar progenitor cells.

  11. New Gene Evolution: Little Did We Know (United States)

    Long, Manyuan; VanKuren, Nicholas W.; Chen, Sidi; Vibranovski, Maria D.


    Genes are perpetually added to and deleted from genomes during evolution. Thus, it is important to understand how new genes are formed and evolve as critical components of the genetic systems determining the biological diversity of life. Two decades of effort have shed light on the process of new gene origination, and have contributed to an emerging comprehensive picture of how new genes are added to genomes, ranging from the mechanisms that generate new gene structures to the presence of new genes in different organisms to the rates and patterns of new gene origination and the roles of new genes in phenotypic evolution. We review each of these aspects of new gene evolution, summarizing the main evidence for the origination and importance of new genes in evolution. We highlight findings showing that new genes rapidly change existing genetic systems that govern various molecular, cellular and phenotypic functions. PMID:24050177

  12. Novel gene transfer systems: intelligent gene transfer vectors for gene medicines. (United States)

    Nakajima, Toshihiro


    Drug delivery systems for gene transfer are called 'vectors'. These systems were originally invented as a delivery system for the transfection in vitro or in vivo. Several vectors are then developed for clinical use of gene medicines and currently some of them are approved as animal drugs. Conventional drug delivery system generally consists of approved (existing) materials to avoid additional pre-clinical or clinical studies. However, current vectors contain novel materials to improve an efficacy of gene medicines. Thus, these vectors have functions more than a mere delivery of active ingredients. For example some vectors have immunological functions such as adjuvants in vaccines. These new types of vectors are called 'intelligent' or 'innovative' vector system', since the concept or strategy for the development is completely different from conventional drug delivery systems. In this article, we described a current status of 'intelligent gene transfer vectors and discussed on the potentials of them.

  13. The biology of novel animal genes: Mouse APEX gene knockout

    Energy Technology Data Exchange (ETDEWEB)

    MacInnes, M.; Altherr, M.R.; Ludwig, D. [Los Alamos National Lab., NM (United States); Pedersen, R.; Mold, C. [Univ. of California, San Francisco, CA (United States)


    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The controlled breeding of novel genes into mice, including the gene knockout (KO), or conversely by adding back transgenes provide powerful genetic technologies that together suffice to determine in large part the biological role(s) of novel genes. Inbred mouse remains the best understood and most useful mammalian experimental system available for tackling the biology of novel genes. The major mammalian apurinic/apyrimidinic (AP) endonuclease (APE), is involved in a key step in the repair of spontaneous and induced AP sites in DNA. Efficient repair of these lesions is imperative to prevent the stable incorporation of mutations into the cellular genome which may lead to cell death or transformation. Loss or modulation of base excison repair activity in vivo may elevate the spontaneous mutation rate in cells, and may lead to a substantial increase in the incidence of cancer. Despite extensive biochemical analysis, however, the significance of these individual APE functions in vivo has not been elucidated. Mouse embryonic stem (ES) cells heterozygous for a deletion mutation in APE have been generated and whole animals containing the APE mutation have been derived from these ES cells. Animals homozygous for the APE null mutation die early in gestation, underscoring the biological significance of this DNA repair gene.

  14. Newer Gene Editing Technologies toward HIV Gene Therapy

    Directory of Open Access Journals (Sweden)

    Premlata Shankar


    Full Text Available Despite the great success of highly active antiretroviral therapy (HAART in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called “Berlin patient” who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy.

  15. Reduced rates of gene loss, gene silencing, and gene mutation in Dnmt1-deficient embryonic stem cells

    NARCIS (Netherlands)

    Chan, M.F.; van Amerongen, R.; Nijjar, T.; Cuppen, E.; Jones, P.A.; Laird, P.W.


    Tumor suppressor gene inactivation is a crucial event in oncogenesis. Gene inactivation mechanisms include events resulting in loss of heterozygosity (LOH), gene mutation, and transcriptional silencing. The contribution of each of these different pathways varies among tumor suppressor genes and by

  16. PoplarGene: poplar gene network and resource for mining functional information for genes from woody plants. (United States)

    Liu, Qi; Ding, Changjun; Chu, Yanguang; Chen, Jiafei; Zhang, Weixi; Zhang, Bingyu; Huang, Qinjun; Su, Xiaohua


    Poplar is not only an important resource for the production of paper, timber and other wood-based products, but it has also emerged as an ideal model system for studying woody plants. To better understand the biological processes underlying various traits in poplar, e.g., wood development, a comprehensive functional gene interaction network is highly needed. Here, we constructed a genome-wide functional gene network for poplar (covering ~70% of the 41,335 poplar genes) and created the network web service PoplarGene, offering comprehensive functional interactions and extensive poplar gene functional annotations. PoplarGene incorporates two network-based gene prioritization algorithms, neighborhood-based prioritization and context-based prioritization, which can be used to perform gene prioritization in a complementary manner. Furthermore, the co-functional information in PoplarGene can be applied to other woody plant proteomes with high efficiency via orthology transfer. In addition to poplar gene sequences, the webserver also accepts Arabidopsis reference gene as input to guide the search for novel candidate functional genes in PoplarGene. We believe that PoplarGene ( and will greatly benefit the research community, facilitating studies of poplar and other woody plants.

  17. Combining gene prediction methods to improve metagenomic gene annotation

    Directory of Open Access Journals (Sweden)

    Rosen Gail L


    Full Text Available Abstract Background Traditional gene annotation methods rely on characteristics that may not be available in short reads generated from next generation technology, resulting in suboptimal performance for metagenomic (environmental samples. Therefore, in recent years, new programs have been developed that optimize performance on short reads. In this work, we benchmark three metagenomic gene prediction programs and combine their predictions to improve metagenomic read gene annotation. Results We not only analyze the programs' performance at different read-lengths like similar studies, but also separate different types of reads, including intra- and intergenic regions, for analysis. The main deficiencies are in the algorithms' ability to predict non-coding regions and gene edges, resulting in more false-positives and false-negatives than desired. In fact, the specificities of the algorithms are notably worse than the sensitivities. By combining the programs' predictions, we show significant improvement in specificity at minimal cost to sensitivity, resulting in 4% improvement in accuracy for 100 bp reads with ~1% improvement in accuracy for 200 bp reads and above. To correctly annotate the start and stop of the genes, we find that a consensus of all the predictors performs best for shorter read lengths while a unanimous agreement is better for longer read lengths, boosting annotation accuracy by 1-8%. We also demonstrate use of the classifier combinations on a real dataset. Conclusions To optimize the performance for both prediction and annotation accuracies, we conclude that the consensus of all methods (or a majority vote is the best for reads 400 bp and shorter, while using the intersection of GeneMark and Orphelia predictions is the best for reads 500 bp and longer. We demonstrate that most methods predict over 80% coding (including partially coding reads on a real human gut sample sequenced by Illumina technology.

  18. COGNATE: comparative gene annotation characterizer. (United States)

    Wilbrandt, Jeanne; Misof, Bernhard; Niehuis, Oliver


    The comparison of gene and genome structures across species has the potential to reveal major trends of genome evolution. However, such a comparative approach is currently hampered by a lack of standardization (e.g., Elliott TA, Gregory TR, Philos Trans Royal Soc B: Biol Sci 370:20140331, 2015). For example, testing the hypothesis that the total amount of coding sequences is a reliable measure of potential proteome diversity (Wang M, Kurland CG, Caetano-Anollés G, PNAS 108:11954, 2011) requires the application of standardized definitions of coding sequence and genes to create both comparable and comprehensive data sets and corresponding summary statistics. However, such standard definitions either do not exist or are not consistently applied. These circumstances call for a standard at the descriptive level using a minimum of parameters as well as an undeviating use of standardized terms, and for software that infers the required data under these strict definitions. The acquisition of a comprehensive, descriptive, and standardized set of parameters and summary statistics for genome publications and further analyses can thus greatly benefit from the availability of an easy to use standard tool. We developed a new open-source command-line tool, COGNATE (Comparative Gene Annotation Characterizer), which uses a given genome assembly and its annotation of protein-coding genes for a detailed description of the respective gene and genome structure parameters. Additionally, we revised the standard definitions of gene and genome structures and provide the definitions used by COGNATE as a working draft suggestion for further reference. Complete parameter lists and summary statistics are inferred using this set of definitions to allow down-stream analyses and to provide an overview of the genome and gene repertoire characteristics. COGNATE is written in Perl and freely available at the ZFMK homepage ( ) and on github ( https

  19. Technology evaluation: HIV ribozyme gene therapy, Gene Shears Pty Ltd. (United States)

    de Feyter, R; Li, P


    Ribozymes (catalytic RNAs) can be made to specifically cleave target RNAs that are involved in disease conditions and therefore have potential as therapeutic agents. Gene Shears Pty Ltd is developing hammerhead ribozyme technology for therapy against HIV infection, targeting either the tat gene or the RNA packaging sequence (Psi) of HIV. These ribozymes have been expressed from constructs that were introduced into hematopoietic cells in culture, thereby protecting the cells against viral infection. Two phase I clinical trials are underway to test the safety and feasibility of the approach with the anti-tat ribozyme in human subjects.

  20. [Gene therapy for Parkinson's disease]. (United States)

    Muramatsu, Shin-Ichi


    The current clinical trials of gene therapy for Parkinson's disease (PD) are based on three strategies. 1. To restore the local production of dopamine by introducing genes associated with dopamine-synthesizing enzymes into the putamen. 2. To protect nigrostriatal projection by delivering the neurturin gene, a trophic factor for dopaminergic neurons, both in the putamen and the substantia nigra. 3. To modulate the neural activity by transducing the subthalamic nucleus with vectors expressing glutamic acid decarboxylase. A phase I clinical study was initiated in 2007 to determine the safety of intra-putaminal infusion of a recombinant adeno-associated virus (AAV) vector encoding aromatic (L)-amino acid decarboxylase (AADC). All six patients enrolled in the trial showed improvements from baseline in the Unified Parkinson's Disease Rating Scale motor scores in the OFF medication state at 36 months after treatment. Although this trial was a small, open-label study and the use of a non-blinded, uncontrolled analysis limits interpretation, the efficacy outcomes are encouraging and indicate that the AAV vector-mediated gene transfer of AADC may benefit advanced PD patients. A similar approach, delivering AAV vector carrying AADC gene into the putamen ameliorated the symptoms in children with AADC deficiency.

  1. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin


    Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

  2. Systems Biophysics of Gene Expression (United States)

    Vilar, Jose M.G.; Saiz, Leonor


    Gene expression is a process central to any form of life. It involves multiple temporal and functional scales that extend from specific protein-DNA interactions to the coordinated regulation of multiple genes in response to intracellular and extracellular changes. This diversity in scales poses fundamental challenges to the use of traditional approaches to fully understand even the simplest gene expression systems. Recent advances in computational systems biophysics have provided promising avenues to reliably integrate the molecular detail of biophysical process into the system behavior. Here, we review recent advances in the description of gene regulation as a system of biophysical processes that extend from specific protein-DNA interactions to the combinatorial assembly of nucleoprotein complexes. There is now basic mechanistic understanding on how promoters controlled by multiple, local and distal, DNA binding sites for transcription factors can actively control transcriptional noise, cell-to-cell variability, and other properties of gene regulation, including precision and flexibility of the transcriptional responses. PMID:23790365

  3. Control of Renin Gene Expression (United States)

    Glenn, Sean T.; Jones, Craig A.; Gross, Kenneth W.; Pan, Li


    Renin, as part of the renin-angiotensin system, plays a critical role in the regulation of blood pressure, electrolyte homeostasis, mammalian renal development and progression of fibrotic/hypertrophic diseases. Renin gene transcription is subject to complex developmental and tissue-specific regulation. Initial studies using the mouse As4.1 cell line, which has many characteristics of the renin-expressing juxtaglomerular cells of the kidney, have identified a proximal promoter region (−197 to −50 bp) and an enhancer (−2866 to −2625 bp) upstream of the Ren-1c gene, which are critical for renin gene expression. The proximal promoter region contains several transcription factor-binding sites including a binding site for the products of the developmental control genes Hox. The enhancer consists of at least 11 transcription factor-binding sites and is responsive to various signal transduction pathways including cAMP, retinoic acid, endothelin-1, and cytokines, all of which are known to alter renin mRNA levels. Furthermore, in vivo models have validated several of these key components found within the proximal promoter region and the enhancer as well as other key sites necessary for renin gene transcription. PMID:22576577

  4. Molecular Studies on Preproinsulin Gene

    Directory of Open Access Journals (Sweden)

    Sabir Sarah


    Full Text Available Insulin plays an important role in maintaining the blood glucose level of the body. The β-cells of pancreas produce insulin in the form of precursor that is preproinsulin. The gene of preproinsulin provides an interesting system for addressing question related to molecular evolution. Recombinant DNA technology has made it possible to isolate and sequence the chromosomal genes coding for unique protein products. Although preproinsulin of various organism has been isolated and cloned, but there is no report from buffalo (Bubalus bubalis that is our major livestock. The genomic DNA of buffalo was isolated using Laura-Lee-Boodram method. The part of preproinsulin gene (596bp and 520bp using BPPI-UPS and bpiful_F as forward and BC1-C as reverse primer was amplified. Cloning of amplified fragments of gene were performed in pCR 2.1 vector. Positive clones were screened on the basis of blue white selection. The band obtained on 596bp and 520bp after colony PCR confirmed the successful cloning of preproinsulin gene in pCR 2.1 vector.

  5. Gene Therapy Applications in Gastroenterology and Hepatology

    Directory of Open Access Journals (Sweden)

    Catherine H Wu


    Full Text Available Advantages and disadvantages of viral vectors and nonviral vectors for gene delivery to digestive organs are reviewed. Advances in systems for the introduction of new gene expression are described, including self-deleting retroviral transfer vectors, chimeric viruses and chimeric oligonucleotides. Systems for inhibition of gene expression are discussed, including antisense oligonucleotides, ribozymes and dominant-negative genes.

  6. Evolving chromosomes and gene regulatory networks

    Indian Academy of Sciences (India)


    Many processes change genomes. Koonin and Wolf. 2008. Page 5 .. including horizontal gene transfer. Koonin and Wolf. 2008. Page 6. Horizontal gene transfer. Drastic modification of genetic material. Rapid exploration of ne niches and phenot pes. Page 7. Horizontal gene transfer regulates. New selective forces for gene ...

  7. A Gene Ontology Tutorial in Python. (United States)

    Vesztrocy, Alex Warwick; Dessimoz, Christophe


    This chapter is a tutorial on using Gene Ontology resources in the Python programming language. This entails querying the Gene Ontology graph, retrieving Gene Ontology annotations, performing gene enrichment analyses, and computing basic semantic similarity between GO terms. An interactive version of the tutorial, including solutions, is available at .

  8. How Gene Patents May Inhibit Scientific Research

    Directory of Open Access Journals (Sweden)

    Campo-Engelstein, Lisa


    Full Text Available In this paper, we point out three possible ways gene patents could impede scientific research. First, gene patent laws might exacerbate the culture of secrecy ubiquitous in science. Second, gene patents may limit researchers’ ability to study poly or multigenic diseases without access to all genetic etiologies. Third, gene patents could result in a “patent thicket”.

  9. Synthetic promoter libraries- tuning of gene expression

    DEFF Research Database (Denmark)

    Hammer, Karin; Mijakovic, Ivan; Jensen, Peter Ruhdal


    The study of gene function often requires changing the expression of a gene and evaluating the consequences. In principle, the expression of any given gene can be modulated in a quasi-continuum of discrete expression levels but the traditional approaches are usually limited to two extremes: gene ...

  10. Deregulated genes in sporadic vestibular schwannomas

    DEFF Research Database (Denmark)

    Cayé-Thomasen, Per; Helweg-Larsen, Rehannah Holga Andrea; Stangerup, Sven-Eric


    In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology.......In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology....

  11. A hybrid approach of gene sets and single genes for the prediction of survival risks with gene expression data. (United States)

    Seok, Junhee; Davis, Ronald W; Xiao, Wenzhong


    Accumulated biological knowledge is often encoded as gene sets, collections of genes associated with similar biological functions or pathways. The use of gene sets in the analyses of high-throughput gene expression data has been intensively studied and applied in clinical research. However, the main interest remains in finding modules of biological knowledge, or corresponding gene sets, significantly associated with disease conditions. Risk prediction from censored survival times using gene sets hasn't been well studied. In this work, we propose a hybrid method that uses both single gene and gene set information together to predict patient survival risks from gene expression profiles. In the proposed method, gene sets provide context-level information that is poorly reflected by single genes. Complementarily, single genes help to supplement incomplete information of gene sets due to our imperfect biomedical knowledge. Through the tests over multiple data sets of cancer and trauma injury, the proposed method showed robust and improved performance compared with the conventional approaches with only single genes or gene sets solely. Additionally, we examined the prediction result in the trauma injury data, and showed that the modules of biological knowledge used in the prediction by the proposed method were highly interpretable in biology. A wide range of survival prediction problems in clinical genomics is expected to benefit from the use of biological knowledge.

  12. Gene conversion in the rice genome

    DEFF Research Database (Denmark)

    Xu, Shuqing; Clark, Terry; Zheng, Hongkun


    than ten percent. Pseudogenes in the rice genome with low similarity to Arabidopsis genes showed greater likelihood for gene conversion than those with high similarity to Arabidopsis genes. Functional annotations suggest that at least 14 multigene families related to disease or bacteria resistance were......BACKGROUND: Gene conversion causes a non-reciprocal transfer of genetic information between similar sequences. Gene conversion can both homogenize genes and recruit point mutations thereby shaping the evolution of multigene families. In the rice genome, the large number of duplicated genes......-chromosomal conversions distributed between chromosome 1 and 5, 2 and 6, and 3 and 5 are more frequent than genome average (Z-test, P

  13. Evolution of Hemoglobin and Its Genes (United States)

    Hardison, Ross C.


    Insights into the evolution of hemoglobins and their genes are an abundant source of ideas regarding hemoglobin function and regulation of globin gene expression. This article presents the multiple genes and gene families encoding human globins, summarizes major events in the evolution of the hemoglobin gene clusters, and discusses how these studies provide insights into regulation of globin genes. Although the genes in and around the α-like globin gene complex are relatively stable, the β-like globin gene clusters are more dynamic, showing evidence of transposition to a new locus and frequent lineage-specific expansions and deletions. The cis-regulatory modules controlling levels and timing of gene expression are a mix of conserved and lineage-specific DNA, perhaps reflecting evolutionary constraint on core regulatory functions shared broadly in mammals and adaptive fine-tuning in different orders of mammals. PMID:23209182

  14. Metagenomics and novel gene discovery (United States)

    Culligan, Eamonn P; Sleator, Roy D; Marchesi, Julian R; Hill, Colin


    Metagenomics provides a means of assessing the total genetic pool of all the microbes in a particular environment, in a culture-independent manner. It has revealed unprecedented diversity in microbial community composition, which is further reflected in the encoded functional diversity of the genomes, a large proportion of which consists of novel genes. Herein, we review both sequence-based and functional metagenomic methods to uncover novel genes and outline some of the associated problems of each type of approach, as well as potential solutions. Furthermore, we discuss the potential for metagenomic biotherapeutic discovery, with a particular focus on the human gut microbiome and finally, we outline how the discovery of novel genes may be used to create bioengineered probiotics. PMID:24317337

  15. Gene Therapy in Cardiac Arrhythmias

    Directory of Open Access Journals (Sweden)

    Praveen S.V


    Full Text Available Gene therapy has progressed from a dream to a bedside reality in quite a few human diseases. From its first application in adenosine deaminase deficiency, through the years, its application has evolved to vascular angiogenesis and cardiac arrhythmias. Gene based biological pacemakers using viral vectors or mesenchymal cells tested in animal models hold much promise. Induction of pacemaker activity within the left bundle branch can provide stable heart rates. Genetic modification of the AV node mimicking beta blockade can be therapeutic in the management of atrial fibrillation. G protein overexpression to modify the AV node also is experimental. Modification and expression of potassium channel genes altering the delayed rectifier potassium currents may permit better management of congenital long QT syndromes. Arrhythmias in a failing heart are due to abnormal calcium cycling. Potential targets for genetic modulation include the sarcoplasmic reticulum calcium pump, calsequestrin and sodium calcium exchanger.Lastly the ethical concerns need to be addressed.

  16. The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study

    DEFF Research Database (Denmark)

    Hedley, Paula L; Haundrup, Ole; Andersen, Paal S


    as well as the T-tubules of the sarcolemma. It has been suggested that minK forms part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to changes in ion channel function. We examined whether mutations in KCNE genes were associated with hypertrophic cardiomyopathy (HCM), a genetic...... disease associated with an improper hypertrophic response....

  17. Candidate Gene Identification of Flowering Time Genes in Cotton

    Directory of Open Access Journals (Sweden)

    Corrinne E. Grover


    Full Text Available Flowering time control is critically important to all sexually reproducing angiosperms in both natural ecological and agronomic settings. Accordingly, there is much interest in defining the genes involved in the complex flowering-time network and how these respond to natural and artificial selection, the latter often entailing transitions in day-length responses. Here we describe a candidate gene analysis in the cotton genus , which uses homologs from the well-described flowering network to bioinformatically and phylogenetically identify orthologs in the published genome sequence from Ulbr., one of the two model diploid progenitors of the commercially important allopolyploid cottons, L. and L. Presence and patterns of expression were evaluated from 13 aboveground tissues related to flowering for each of the candidate genes using allopolyploid as a model. Furthermore, we use a comparative context to determine copy number variability of each key gene family across 10 published angiosperm genomes. Data suggest a pattern of repeated loss of duplicates following ancient whole-genome doubling events in diverse lineages. The data presented here provide a foundation for understanding both the parallel evolution of day-length neutrality in domesticated cottons and the flowering-time network, in general, in this important crop plant.

  18. Effect Alpha Globlin Gene Deletion And Gamma Globin Gene -158 ...

    African Journals Online (AJOL)

    We studied the Xmn1 polymorphism (C/T) in γ- globin gene position -158 of β- thalassemia as a modulating factor of the disease severity. Presence of the polymorphism was found in two patients and this was not sufficient to explain the diversity of the phenotype encountered. Co-inheritance of alpha thalassaemia as a ...

  19. FunGeneClusterS

    DEFF Research Database (Denmark)

    Vesth, Tammi Camilla; Brandl, Julian; Andersen, Mikael Rørdam


    and industrial biotechnology applications. We have previously published a method for accurate prediction of clusters from genome and transcriptome data, which could also suggest cross-chemistry, however, this method was limited both in the number of parameters which could be adjusted as well as in user......Secondary metabolites of fungi are receiving an increasing amount of interest due to their prolific bioactivities and the fact that fungal biosynthesis of secondary metabolites often occurs from co-regulated and co-located gene clusters. This makes the gene clusters attractive for synthetic biology...

  20. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder


    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each......%). Fifteen nuclear encoded mitochondrial proteins were all down-regulated in CRC. We identified several chromosomal locations with clusters of either potential oncogenes or potential tumor suppressors. Some of these, such as aminopeptidase N/CD13 and sigma B3 protein on chromosome 15q25, coincided...

  1. Does inbreeding affect gene expression in birds? (United States)

    Hansson, Bengt; Naurin, Sara; Hasselquist, Dennis


    Inbreeding increases homozygosity, exposes genome-wide recessive deleterious alleles and often reduces fitness. The physiological and reproductive consequences of inbreeding may be manifested already during gene regulation, but the degree to which inbreeding influences gene expression is unknown in most organisms, including in birds. To evaluate the pattern of inbreeding-affected gene expression over the genome and in relation to sex, we performed a transcriptome-wide gene expression (10 695 genes) study of brain tissue of 10-day-old inbred and outbred, male and female zebra finches. We found significantly lower gene expression in females compared with males at Z-linked genes, confirming that dosage compensation is incomplete in female birds. However, inbreeding did not affect gene expression at autosomal or sex-linked genes, neither in males nor in females. Analyses of single genes again found a clear sex-biased expression at Z-linked genes, whereas only a single gene was significantly affected by inbreeding. The weak effect of inbreeding on gene expression in zebra finches contrasts to the situation, for example, in Drosophila where inbreeding has been found to influence gene expression more generally and at stress-related genes in particular. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  2. Integrones: los coleccionistas de genes Integrons: gene collectors

    Directory of Open Access Journals (Sweden)

    J. A. Di Conza


    Full Text Available Los integrones son estructuras genéticas que han despertado gran interés, debido a que algunos de ellos vehiculizan genes de resistencia a los antimicrobianos. Están formados por un fragmento que codifica una integrasa (intI y, a continuación, una secuencia attI a la que se unen los genes en casetes que codifican diferentes mecanismos de resistencia. Dentro de intI, en su extremo 3´, hay una secuencia promotora Pc a partir de la cual se transcriben los casetes de resistencia integrados, ya que estos genes carecen de promotor. Sin embargo, estos casetes presentan una secuencia específica denominada attC, la cual es reconocida por la integrasa que se une, por recombinación, a la secuencia attI del integrón en la orientación adecuada para su expresión. Los integrones se han clasificado según la secuencia de su integrasa, pero en la actualidad se prefiere clasificarlos según su localización. Se habla, en general, de "integrones móviles" para referirse a aquellos asociados a secuencias de inserción, transposones y/o plásmidos conjugativos, los que en su mayoría median mecanismos de resistencia, y de "superintegrones", de localización cromosómica y con grandes arreglos de genes en casetes. Los integrones móviles de clase 1 son los más abundantes en aislamientos clínicos y suelen estar asociados a transposones del subgrupo Tn21, seguidos por los de clase 2, derivados principalmente de Tn7. Estos elementos no son móviles por sí mismos, pero su asociación con elementos que sí lo son facilita su transferencia horizontal, lo que explica su amplia difusión entre las bacterias. Esta revisión intenta recopilar la información disponible acerca de los integrones móviles descritos en Argentina hasta la fecha.Integrons gained great interest due to their participation in resistance gene recruitment and expression. Their basic structure includes a fragment that encodes an integrase (intI followed by a recognition sequence (attI into

  3. Detecting Sequence Homology at the Gene Cluster Level with MultiGeneBlast

    NARCIS (Netherlands)

    Medema, Marnix H.; Takano, Eriko; Breitling, Rainer; Nowick, Katja

    The genes encoding many biomolecular systems and pathways are genomically organized in operons or gene clusters. With MultiGeneBlast, we provide a user-friendly and effective tool to perform homology searches with operons or gene clusters as basic units, instead of single genes. The

  4. Machine Learning-Based Gene Prioritization Identifies Novel Candidate Risk Genes for Inflammatory Bowel Disease. (United States)

    Isakov, Ofer; Dotan, Iris; Ben-Shachar, Shay


    The inflammatory bowel diseases (IBDs) are chronic inflammatory disorders, associated with genetic, immunologic, and environmental factors. Although hundreds of genes are implicated in IBD etiology, it is likely that additional genes play a role in the disease process. We developed a machine learning-based gene prioritization method to identify novel IBD-risk genes. Known IBD genes were collected from genome-wide association studies and annotated with expression and pathway information. Using these genes, a model was trained to identify IBD-risk genes. A comprehensive list of 16,390 genes was then scored and classified. Immune and inflammatory responses, as well as pathways such as cell adhesion, cytokine-cytokine receptor interaction, and sulfur metabolism were identified to be related to IBD. Scores predicted for IBD genes were significantly higher than those for non-IBD genes (P genes had a high prediction score (>0.8). A literature review of the genes, excluding those used to train the model, identified 67 genes without any publication concerning IBD. These genes represent novel candidate IBD-risk genes, which can be targeted in future studies. Our method successfully differentiated IBD-risk genes from non-IBD genes by using information from expression data and a multitude of gene annotations. Crucial features were defined, and we were able to detect novel candidate risk genes for IBD. These findings may help detect new IBD-risk genes and improve the understanding of IBD pathogenesis.

  5. Interactive visualization of gene regulatory networks with associated gene expression time series data

    NARCIS (Netherlands)

    Westenberg, Michel A.; Hijum, Sacha A.F.T. van; Lulko, Andrzej T.; Kuipers, Oscar P.; Roerdink, Jos B.T.M.; Linsen, L; Hagen, H; Hamann, B


    We present GENeVis, an application to visualize gene expression time series data in a gene regulatory network context. This is a network of regulator proteins that regulate the expression of their respective target genes. The networks are represented as graphs, in which the nodes represent genes,

  6. A gene-based information gain method for detecting gene-gene interactions in case-control studies. (United States)

    Li, Jin; Huang, Dongli; Guo, Maozu; Liu, Xiaoyan; Wang, Chunyu; Teng, Zhixia; Zhang, Ruijie; Jiang, Yongshuai; Lv, Hongchao; Wang, Limei


    Currently, most methods for detecting gene-gene interactions (GGIs) in genome-wide association studies are divided into SNP-based methods and gene-based methods. Generally, the gene-based methods can be more powerful than SNP-based methods. Some gene-based entropy methods can only capture the linear relationship between genes. We therefore proposed a nonparametric gene-based information gain method (GBIGM) that can capture both linear relationship and nonlinear correlation between genes. Through simulation with different odds ratio, sample size and prevalence rate, GBIGM was shown to be valid and more powerful than classic KCCU method and SNP-based entropy method. In the analysis of data from 17 genes on rheumatoid arthritis, GBIGM was more effective than the other two methods as it obtains fewer significant results, which was important for biological verification. Therefore, GBIGM is a suitable and powerful tool for detecting GGIs in case-control studies.

  7. Gene therapy on demand: site specific regulation of gene therapy. (United States)

    Jazwa, Agnieszka; Florczyk, Urszula; Jozkowicz, Alicja; Dulak, Jozef


    Since 1990 when the first clinical gene therapy trial was conducted, much attention and considerable promise have been given to this form of treatment. Gene therapy has been used with success in patients suffering from severe combined immunodeficiency syndromes (X-SCID and ADA-deficiency), Leber's congenital amaurosis, hemophilia, β-thalassemia and adrenoleukodystrophy. Last year, the first therapeutic vector (Glybera) for treatment of lipoprotein lipase deficiency has been registered in the European Union. Nevertheless, there are still several numerous issues that need to be improved to make this technique more safe, effective and easily accessible for patients. Introduction of the therapeutic gene to the given cells should provide the level of expression which will restore the production of therapeutic protein to normal values or will provide therapeutic efficacy despite not fully physiological expression. However, in numerous diseases the expression of therapeutic genes has to be kept at certain level for some time, and then might be required to be switched off to be activated again when worsening of the symptoms may aggravate the risk of disease relapse. In such cases the promoters which are regulated by local conditions may be more required. In this article the special emphasis is to discuss the strategies of regulation of gene expression by endogenous stimuli. Particularly, the hypoxia- or miRNA-regulated vectors offer the possibilities of tight but, at the same time, condition-dependent and cell-specific expression. Such means have been already tested in certain pathophysiological conditions. This creates the chance for the translational approaches required for development of effective treatments of so far incurable diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Combined RNA interference of adenine nucleotide translocase-2 and ganciclovir therapy in hepatocellular carcinoma. (United States)

    Kim, Jung Eun; Hwang, Mi-Hye; Lee, Ho Won; Lee, Sang-Woo; Lee, Jaetae; Ahn, Byeong-Cheol


    The purpose of this study was to investigate the anticancer effects of combined RNA interference (RNAi) of the adenine nucleotide translocase-2 (ANT2) gene and ganciclovir (GCV) therapy for treatment of hepatocellular carcinoma cells (Huh 7) in an animal model. The Huh 7/NTG stable cell line was established by transfection of a vector with the human sodium iodide symporter (hNIS), HSV1-sr39 thymidine kinase (tk), and enhanced green florescent protein (EGFP) fusion gene into Huh 7 cells. mRNA expressions of these genes were evaluated by RT-PCR analysis. The functions of hNIS and HSV1-sr39tk were verified with (125)I uptake and (3)H-penciclovir (PCV) uptake tests. EGFP and hNIS expression was confirmed with confocal microscopy after immunocytochemical staining. We treated the tumor cells with ANT2 shRNA or GCV or both ANT2 shRNA and GCV and treated the in vivo mouse model with a Huh 7/NTG tumor xenograft. The therapeutic effects of the in vivo study were assessed with caliper measurements and gamma camera imaging using (99m)Tc-pertechnetate. Huh 7/NTG cells showed a cell number-dependent increase in (125)I uptake and a 24-fold higher (3)H-PCV uptake compared to parent Huh 7 cells. Huh 7/NTG cells transfected with ANT2 shRNA had lower ANT2 mRNA expression and more impaired proliferation activity than cells transfected with scramble shRNA. Proliferation of Huh 7/NTG cells was also inhibited by GCV treatment. Combined GCV and ANT2 shRNA therapy further inhibited cell proliferation in the in vitro study. The combined therapy with GCV and ANT2 shRNA showed a further decrease in tumor growth in the mouse model. Our results suggest that the combined RNA interference with ANT2 and GCV therapy inhibited hepatocellular carcinoma cell proliferation more than single GCV therapy or ANT2 shRNA therapy in vitro and in vivo. Therefore it could be applied treating incurable hepatocellular carcinoma. © 2013.

  9. Persistence drives gene clustering in bacterial genomes

    Directory of Open Access Journals (Sweden)

    Rocha Eduardo PC


    Full Text Available Abstract Background Gene clustering plays an important role in the organization of the bacterial chromosome and several mechanisms have been proposed to explain its extent. However, the controversies raised about the validity of each of these mechanisms remind us that the cause of this gene organization remains an open question. Models proposed to explain clustering did not take into account the function of the gene products nor the likely presence or absence of a given gene in a genome. However, genomes harbor two very different categories of genes: those genes present in a majority of organisms – persistent genes – and those present in very few organisms – rare genes. Results We show that two classes of genes are significantly clustered in bacterial genomes: the highly persistent and the rare genes. The clustering of rare genes is readily explained by the selfish operon theory. Yet, genes persistently present in bacterial genomes are also clustered and we try to understand why. We propose a model accounting specifically for such clustering, and show that indispensability in a genome with frequent gene deletion and insertion leads to the transient clustering of these genes. The model describes how clusters are created via the gene flux that continuously introduces new genes while deleting others. We then test if known selective processes, such as co-transcription, physical interaction or functional neighborhood, account for the stabilization of these clusters. Conclusion We show that the strong selective pressure acting on the function of persistent genes, in a permanent state of flux of genes in bacterial genomes, maintaining their size fairly constant, that drives persistent genes clustering. A further selective stabilization process might contribute to maintaining the clustering.

  10. Gene-gene and gene-environment interaction on the risk of Parkinson's disease. (United States)

    Singh, Neeraj Kumar; Banerjee, Basu Dev; Bala, Kiran; Chhillar, Mitrabasu; Chhillar, Neelam


    Even with numerous studies the cause of Parkinson's disease (PD) remains elusive. It has been hypothesized that interactions between genetic and environmental factors may play an important role in the pathogenesis of PD. To examine the gene-gene and gene-environment interaction on PD risk with respect to gene polymorphism of cytochrome P450 2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1), organochlorine pesticides (OCPs) and metals. This study included 70 patients of PD and 100 age-matched controls. The restriction fragment length polymorphism was used for analysis of genetic polymorphism. OCPs and serum metal levels were estimated by using gas chromatography and an autoanalyser respectively. The CYP2D6*4 mt and GSTP1 *B allelic variants were significantly associated with increase in PD risk. We found a statistically significant difference in β -hexachlorocyclohexane (β-HCH), dieldrin, 1,1-dichloro-2,2-bis(pchlorophenyl) ethylene (pp'-DDE) and copper levels between the patients and controls. We found significantly high levels of β-HCH, dieldrin and pp'-DDE in the CYP2D6*4 mt allelic variants, β-HCH and pp'-DDE in the GSTP1*B allelic variants and dieldrin in the GSTP1*C allelic variants when comparing CYP2D6*4 non-mt, GSTP1 non-*B and GSTP1 non-*C allelic variants in patients of PD respectively. This study demonstrates that the CYP2D6*4 and GSTP1 genes may be considered as candidate genes for PD and they may also interact with β- HCH, dieldrin and pp'-DDE to influence the risk for PD.

  11. Genome position and gene amplification

    Czech Academy of Sciences Publication Activity Database

    Jirsová, Pavla; Snijders, A.M.; Kwek, S.; Roydasgupta, R.; Fridlyand, J.; Tokuyasu, T.; Pinkel, D.; Albertson, D. G.


    Roč. 8, č. 6 (2007), r120 ISSN 1474-760X Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : gene amplification * array comparative genomic hybridization * oncogene Subject RIV: BO - Biophysics Impact factor: 6.589, year: 2007

  12. Positional cloning of deafness genes

    NARCIS (Netherlands)

    Kremer, H.; Cremers, F.P.M.


    The identification of the majority of the known causative genes involved in nonsyndromic sensorineural hearing loss (NSHL) started with linkage analysis as part of a positional cloning procedure. The human and mouse genome projects in combination with technical developments on genotyping,

  13. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism ...

    African Journals Online (AJOL)

    Polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are associated with abortion, early embryo loss and recurrent spontaneous abortion in human. However, information on the association between MTHFR polymorphism and cow abortion is scarce. In the present study, the effects of MTHFR ...

  14. (TNNC1) gene in goat

    African Journals Online (AJOL)



    Feb 23, 2012 ... that TNNC1 was a 161-amino acid polypeptide that had been highly conserved during evolution. Its ... patterns and evolution of TNNC1 gene in animal. .... Dog. 93.00. 98.76. EM. XM533799.2. Genbank. Oryctolagus cuniculus. Rabbit. 90.74. 99.38. EM. XM002713240.1 Genbank. Mus musculus. Mouse.

  15. Sculpting the Barnyard Gene Pool (United States)

    Childers, Gina; Wolfe, Kim; Dupree, Alan; Young, Sheila; Caver, Jessica; Quintanilla, Ruby; Thornton, Laura


    Project-based learning (PBL) takes student engagement to a higher level through reflective collaboration, inquiry, critical thinking, problem solving, and personal relevance. This article explains how six high school teachers developed an interconnected, interdisciplinary STEM-focused PBL called "Sculpting the Barnyard Gene Pool." The…

  16. Gene expression profile of pulpitis (United States)

    Galicia, Johnah C.; Henson, Brett R.; Parker, Joel S.; Khan, Asma A.


    The cost, prevalence and pain associated with endodontic disease necessitate an understanding of the fundamental molecular aspects of its pathogenesis. This study was aimed to identify the genetic contributors to pulpal pain and inflammation. Inflamed pulps were collected from patients diagnosed with irreversible pulpitis (n=20). Normal pulps from teeth extracted for various reasons served as controls (n=20). Pain level was assessed using a visual analog scale (VAS). Genome-wide microarray analysis was performed using Affymetrix GeneTitan Multichannel Instrument. The difference in gene expression levels were determined by the Significance Analysis of Microarray program using a false discovery rate (q-value) of 5%. Genes involved in immune response, cytokine-cytokine receptor interaction and signaling, integrin cell surface interactions, and others were expressed at relatively higher levels in the in the pulpitis group. Moreover, several genes known to modulate pain and inflammation showed differential expression in asymptomatic and mild pain patients (≥30mm on VAS) compared to those with moderate to severe pain. This exploratory study provides a molecular basis for the clinical diagnosis of pulpitis. With an enhanced understanding of pulpal inflammation, future studies on treatment and management of pulpitis and on pain associated with it can have a biological reference to bridge treatment strategies with pulpal biology. PMID:27052691

  17. Gene Expression in Trypanosomatid Parasites

    Directory of Open Access Journals (Sweden)

    Santiago Martínez-Calvillo


    Full Text Available The parasites Leishmania spp., Trypanosoma brucei, and Trypanosoma cruzi are the trypanosomatid protozoa that cause the deadly human diseases leishmaniasis, African sleeping sickness, and Chagas disease, respectively. These organisms possess unique mechanisms for gene expression such as constitutive polycistronic transcription of protein-coding genes and trans-splicing. Little is known about either the DNA sequences or the proteins that are involved in the initiation and termination of transcription in trypanosomatids. In silico analyses of the genome databases of these parasites led to the identification of a small number of proteins involved in gene expression. However, functional studies have revealed that trypanosomatids have more general transcription factors than originally estimated. Many posttranslational histone modifications, histone variants, and chromatin modifying enzymes have been identified in trypanosomatids, and recent genome-wide studies showed that epigenetic regulation might play a very important role in gene expression in this group of parasites. Here, we review and comment on the most recent findings related to transcription initiation and termination in trypanosomatid protozoa.

  18. 06 Silence of the Genes

    Indian Academy of Sciences (India)


    April 2007 Volume 12 Number 4. GENERAL ARTICLES. 06 Silence of the Genes. 2006 Nobel Prize in Physiology or Medicine. Utpal Nath and Saumitra Das. 19 Euclid and 'The Elements'. C R Pranesachar. 26 Euclid's Fifth Postulate. Renuka Ravindran. 37 Decoding Reed–Solomon Codes Using Euclid's. Algorithm.

  19. Gene expression profile of pulpitis. (United States)

    Galicia, J C; Henson, B R; Parker, J S; Khan, A A


    The cost, prevalence and pain associated with endodontic disease necessitate an understanding of the fundamental molecular aspects of its pathogenesis. This study was aimed to identify the genetic contributors to pulpal pain and inflammation. Inflamed pulps were collected from patients diagnosed with irreversible pulpitis (n=20). Normal pulps from teeth extracted for various reasons served as controls (n=20). Pain level was assessed using a visual analog scale (VAS). Genome-wide microarray analysis was performed using Affymetrix GeneTitan Multichannel Instrument. The difference in gene expression levels were determined by the significance analysis of microarray program using a false discovery rate (q-value) of 5%. Genes involved in immune response, cytokine-cytokine receptor interaction and signaling, integrin cell surface interactions, and others were expressed at relatively higher levels in the pulpitis group. Moreover, several genes known to modulate pain and inflammation showed differential expression in asymptomatic and mild pain patients (⩾30 mm on VAS) compared with those with moderate to severe pain. This exploratory study provides a molecular basis for the clinical diagnosis of pulpitis. With an enhanced understanding of pulpal inflammation, future studies on treatment and management of pulpitis and on pain associated with it can have a biological reference to bridge treatment strategies with pulpal biology.

  20. Ethics of Gene Therapy Debated. (United States)

    Borman, Stu


    Presented are the highlights of a press conference featuring biomedical ethicist LeRoy Walters of Georgetown University and attorney Andrew Kimbrell of the Foundation on Economic Trends. The opposing points of view of these two speakers serve to outline the pros and cons of the gene therapy issue. (CW)

  1. Embryos, genes, and birth defects

    National Research Council Canada - National Science Library

    Ferretti, Patrizia


    ... Structural anomalies The genesis of chromosome abnormalities Embryo survival The cause of high levels of chromosome abnormality in human embryos Relative parental risks - age, translocations, inversions, gonadal and germinal mosaics 33 33 34 35 36 44 44 45 4 Identification and Analysis of Genes Involved in Congenital Malformation Syndromes Peter J. Scambler Ge...

  2. Patching genes to fight disease

    Energy Technology Data Exchange (ETDEWEB)

    Holzman, D.


    The National Institutes of Health has approved the first gene therapy experiments, one of which will try to cure cancer by bolstering the immune system. The applications of such therapy are limited, but the potential aid to people with genetic diseases is great.

  3. The Language of the Genes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 3. The Language of the Genes Linking the Past and the Future. Amitabh Joshi ... Author Affiliations. Amitabh Joshi1. Animal Behaviour Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O., Bangalore 560 064, India.

  4. Homeobox genes and melatonin synthesis

    DEFF Research Database (Denmark)

    Rohde, Kristian; Møller, Morten; Rath, Martin Fredensborg


    Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based indu......Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a c......AMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX......) transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating c...

  5. [Chromosomal rearrangements and fusion genes in carcinoma]. (United States)

    Massard, Christophe; Auger, Nathalie; Lacroix, Ludovic; Bénard, Jean


    In the last decades, rarity of chromosomal rearrangements and fusion genes detected in epithelial cancers in using classical karyotyping led to consider these genomic events as specifically restricted to haematological neoplasia and mesenchymal tumors. Today, gene positioning as well as bio-informatics approaches has enabled identifying in carcinoma various fusion genes subsequent to chromosomal translocations, inversions, or deletions. Thus, gene fusion formation appears as a common mechanism in oncology that concerns most of human cancers, independent of original tissue lineage. At a clinical point of view, applications of fusion genes in terms of diagnosis, prognosis and therapeutics can be envisioned. This review will present current knowledge about fusion genes in common carcinoma (prostate, breast, colon). Following a structural and functional description of various fusion genes so far found in human malignant solid tumors, as well as techniques used for their detection, the review will integrate fusion genes in epithelia oncogenesis general scheme. Finally, promising clinical issues of fusion genes will be surveyed.

  6. The combinatorics of overlapping genes. (United States)

    Lèbre, Sophie; Gascuel, Olivier


    Overlapping genes exist in all domains of life and are much more abundant than expected upon their first discovery in the late 1970s. Assuming that the reference gene is read in frame +0, an overlapping gene can be encoded in two reading frames in the sense strand, denoted by +1 and +2, and in three reading frames in the opposite strand, denoted by -0, -1, and -2. This motivated numerous researchers to study the constraints induced by the genetic code on the various overlapping frames, mostly based on information theory. Our focus in this paper is on the constraints induced on two overlapping genes in terms of amino acids, as well as polypeptides. We show that simple linear constraints bind the amino-acid composition of two proteins encoded by overlapping genes. Novel constraints are revealed when polypeptides are considered, and not just single amino acids. For example, in double-coding sequences with an overlapping reading