Background 131Ⅰ therapy is recognized as the simplest, safest, least expensive, and most effective treatment, and accepted by more and more patients. However its curative effect is influenced by many factors, therefo...Background 131Ⅰ therapy is recognized as the simplest, safest, least expensive, and most effective treatment, and accepted by more and more patients. However its curative effect is influenced by many factors, therefore there are some difficulties for doctors to establish individual treatment strategy. The aims of this study were to determine the incidence of early and late hypothyroidism after 131Ⅰ treatment for Graves＇ disease （GD） and to compare their correlation, to observe and analyze the influential factors and to understand the predictabilities of them.Methods Five hundred GD patients （144 males, 356 females; age （41.2±12.3） years） received 131Ⅰ treatment for the first time. The therapeutic procedure was carried out as the following： undergoing 131Ⅰ uptake test to obtain maximum of thyroid uptake value and effective half-life （EHL） time; estimating the thyroid＇s weight by ultrasonography; determination of thyroid hormones and correlative antibodies; pre-therapy physical examination; thyroid imaging; calculating 131Ⅰtherapeutic dosage; per os uptake of the determined 131Ⅰ dosage; follow-up appraisal of curative effect. The observing parameters included age, gender, thyroid weight, GD duration, condition of onset, state of disease, course of treatment, EHL time, maximum of thyroid uptake value, 131Ⅰ dosage and titer of correlative antibodies. We sorted out the data and used both univariate and multivariate analysis to evaluate them statistically.Results The incidence rates of early and late hypothyroidism were 33.2% and 6.6% respectively after 131Ⅰ treatment and approximately 22.2% cases of late hypothyroidism developed from early hypothyroidism. The influential factors of early hypothyroidism included course of GD, the highest thyroid uptake ratio of 131Ⅰ, EHL time and thyroid microsome antibody （TMAb）, etc. A multivariate analysis on late hypothyroidism showed that female patients, with recurrence after anti-thyroid drug treatment and higher thyroid weight, had lower possibility of late hypothyroidism after 131Ⅰ therapy.Conclusions The incidence of early hypothyroidism is higher than that of late hypothyroidism. The highest thyroid uptake ratio of 131Ⅰ, EHL and TMAb will increase the possibility of early hypothyroidism, while GD course is the protective factor. Higher 131Ⅰ dosage, longer EHL and higher TMAb titer will also increase the possibility of late hypothyroidism. The multi-perspective and multi-factor analysis has the benefit to establish individualized treatment strategy.展开更多
Norepinephrine transporter （NET） transfection leads to significant uptake of iodine-131-labeled metaiodobenzylguanidine （^131I-MIBG） in non-neuroendocrine tumors. However, the use of ^131I-MIBG is limited by its s...Norepinephrine transporter （NET） transfection leads to significant uptake of iodine-131-labeled metaiodobenzylguanidine （^131I-MIBG） in non-neuroendocrine tumors. However, the use of ^131I-MIBG is limited by its short retention time in target cells. To prolong the retention of ^131I-MIBG in target cells, we infected hepatocarcinoma （HepG2） cells with Lentivirus-encoding human NET and vesicular monoamine transporter 2 （VMAT2） genes to obtain NET-expressing, NET-VMAT2-coexpressing, and negative-control cell lines. We evaluated the uptake and efflux of 131I-MIBG both in vitro and in vivo in mice bearing transfected tumors. NET- expressing and NET-VMAT2-coexpressing cells respectively showed 2.24 and 2.22 times higher ^131I-MIBG uptake than controls. Two hours after removal of ^131I-MIBG-containing medium, 25.4% efflux was observed in NET- VMAT2-coexpressing cells and 38.6% in NET-expressing cells. In vivo experiments were performed in nude mice bearing transfected tumors; results revealed that NET-VMAT2-coexpressing tumors had longer ^131I-MIBG retention time than NET-expressing tumors. Meanwhile, NET-VMAT2-coexpressing and NET-expressing tumors displayed 0.54% and 0.19%, respectively, of the injected dose per gram of tissue 24 h after ^131I-MIBG administration. Cotransfection of HepG2 cells with NET and VMAT2 resulted in increased ^131I-MIBG uptake and retention. However, the degree of increase was insufficient to be therapeutically effective in target cells.展开更多
文摘Background 131Ⅰ therapy is recognized as the simplest, safest, least expensive, and most effective treatment, and accepted by more and more patients. However its curative effect is influenced by many factors, therefore there are some difficulties for doctors to establish individual treatment strategy. The aims of this study were to determine the incidence of early and late hypothyroidism after 131Ⅰ treatment for Graves＇ disease （GD） and to compare their correlation, to observe and analyze the influential factors and to understand the predictabilities of them.Methods Five hundred GD patients （144 males, 356 females; age （41.2±12.3） years） received 131Ⅰ treatment for the first time. The therapeutic procedure was carried out as the following： undergoing 131Ⅰ uptake test to obtain maximum of thyroid uptake value and effective half-life （EHL） time; estimating the thyroid＇s weight by ultrasonography; determination of thyroid hormones and correlative antibodies; pre-therapy physical examination; thyroid imaging; calculating 131Ⅰtherapeutic dosage; per os uptake of the determined 131Ⅰ dosage; follow-up appraisal of curative effect. The observing parameters included age, gender, thyroid weight, GD duration, condition of onset, state of disease, course of treatment, EHL time, maximum of thyroid uptake value, 131Ⅰ dosage and titer of correlative antibodies. We sorted out the data and used both univariate and multivariate analysis to evaluate them statistically.Results The incidence rates of early and late hypothyroidism were 33.2% and 6.6% respectively after 131Ⅰ treatment and approximately 22.2% cases of late hypothyroidism developed from early hypothyroidism. The influential factors of early hypothyroidism included course of GD, the highest thyroid uptake ratio of 131Ⅰ, EHL time and thyroid microsome antibody （TMAb）, etc. A multivariate analysis on late hypothyroidism showed that female patients, with recurrence after anti-thyroid drug treatment and higher thyroid weight, had lower possibility of late hypothyroidism after 131Ⅰ therapy.Conclusions The incidence of early hypothyroidism is higher than that of late hypothyroidism. The highest thyroid uptake ratio of 131Ⅰ, EHL and TMAb will increase the possibility of early hypothyroidism, while GD course is the protective factor. Higher 131Ⅰ dosage, longer EHL and higher TMAb titer will also increase the possibility of late hypothyroidism. The multi-perspective and multi-factor analysis has the benefit to establish individualized treatment strategy.
基金We thank Yuanyou Yang, PhD, for helping in the preparation of ^131I- MIBG. This study was fimded by the National Natural Science Foundation of China （No. 81271602）.
文摘Norepinephrine transporter （NET） transfection leads to significant uptake of iodine-131-labeled metaiodobenzylguanidine （^131I-MIBG） in non-neuroendocrine tumors. However, the use of ^131I-MIBG is limited by its short retention time in target cells. To prolong the retention of ^131I-MIBG in target cells, we infected hepatocarcinoma （HepG2） cells with Lentivirus-encoding human NET and vesicular monoamine transporter 2 （VMAT2） genes to obtain NET-expressing, NET-VMAT2-coexpressing, and negative-control cell lines. We evaluated the uptake and efflux of 131I-MIBG both in vitro and in vivo in mice bearing transfected tumors. NET- expressing and NET-VMAT2-coexpressing cells respectively showed 2.24 and 2.22 times higher ^131I-MIBG uptake than controls. Two hours after removal of ^131I-MIBG-containing medium, 25.4% efflux was observed in NET- VMAT2-coexpressing cells and 38.6% in NET-expressing cells. In vivo experiments were performed in nude mice bearing transfected tumors; results revealed that NET-VMAT2-coexpressing tumors had longer ^131I-MIBG retention time than NET-expressing tumors. Meanwhile, NET-VMAT2-coexpressing and NET-expressing tumors displayed 0.54% and 0.19%, respectively, of the injected dose per gram of tissue 24 h after ^131I-MIBG administration. Cotransfection of HepG2 cells with NET and VMAT2 resulted in increased ^131I-MIBG uptake and retention. However, the degree of increase was insufficient to be therapeutically effective in target cells.
