Dosimetry of radioiodine therapy in patients with nodular goiter after pretreatment with a single, low dose of recombinant human thyroid-stimulating hormone.

A single, low dose of recombinant human thyroid-stimulating hormone (rhTSH) doubles 24-h RAIU and causes a more homogeneous distribution of radioiodine on thyroid scintigrams of patients with nodular goiter. Pretreatment with rhTSH allows the therapeutic dose of (131)I to be reduced by 50%-60% without compromising the result of thyroid volume reduction. The present study focused on the dosimetric aspects of therapy with a reduced dose of (131)I after pretreatment with rhTSH in patients with nodular goiter. METHODS: Thirty-six patients were treated with (131)I to reduce thyroid volume. Nine patients were pretreated with a single dose of 0.01 mg of rhTSH, and 9 patients, with 0.03 mg of rhTSH. Two control groups of 9 patients, matched for thyroid weight and 24-h radioactive iodide uptake, were not pretreated with rhTSH. The therapeutic dose of (131)I was aimed at being sufficient to result in retention of 3.7 MBq of (131)I per gram of thyroid tissue at 24 h. Thyroid radioactivity after (131)I administration was measured every 24 h for 3 d and on days 7, 10, 14, 21, and 28. A model of iodine biokinetics was used to estimate absorbed doses in organs. Protein-bound (131)I activity was measured at 1, 2, 3, 7, and 10 d and at 2, 3, and 4 wk after (131)I therapy. RESULTS: The administered activities were 1.5 times lower in the 0.01-mg rhTSH group and 1.9 times lower in the 0.03-mg rhTSH group than in the control groups. The absorbed dose in the thyroid was similar in the rhTSH-pretreated groups and in the control groups. In the organs of excretion (bladder) and uptake (stomach) of inorganic iodide, the absorbed doses were 2- to 3-fold lower in the pretreated groups than in the control groups. The effective dose equivalent outside the thyroid was considerably lower in the rhTSH-pretreated groups than in their respective control groups (1.6-fold in the 0.01-mg rhTSH group and 2.3-fold in the 0.03-mg rhTSH group). The time course of protein-bound (131)I activity in serum and the cumulated protein-bound (131)I activity in serum did not differ significantly between rhTSH-pretreated and control groups. CONCLUSION: (131)I therapy after pretreatment with a single, low dose of rhTSH, with the dose reduced according to the rhTSH-induced increase in 24-h radioactive iodide uptake, caused lower radiation-absorbed doses in extrathyroidal organs and tissues, especially bladder and stomach, and no significant increase in the release of (131)I-labeled thyroid hormones into the circulation of patients with nodular goiter. Thus, this mode of therapy can be recommended, especially when the dose of radioiodine to be administered without rhTSH pretreatment is high.     

131Ⅰ治疗Graves病783例疗效观察及影响因素分析

目的 观察131Ⅰ治疗甲状腺功能亢进症(甲亢)的疗效及分析影响因素.方法 Graves病患者783例,服用131Ⅰ前记录患者性别、年龄、病程、甲状腺肿大程度和性质、甲亢程度、服用抗甲状腺药(ATD)情况、甲状腺质量、有否结节、24h摄131Ⅰ率、131Ⅰ总剂量、每克甲状腺给予131Ⅰ剂量、血清甲状腺激素及甲状腺自身抗体水平,量化各指标值,治疗3、6、12及24个月后分别观察患者症状和体征的变化情况,按完全缓解(包括甲状腺功能减退症)、部分缓解进行评价.统计分析使用SAS8.2软件包,采用CMH卡方检验(CMHχ2)、Wilcoxon秩和检验及Logistic回归.结果 疗效与服用131Ⅰ后的时间存在线性关系(CMHχ2=69.21,P＜0.01);服用131Ⅰ12个月后甲状腺质量、急躁、易惊、食欲亢进、心悸等症状和体征均有明显的改善(P值均＜0.05);Logistic回归结果显示:年龄、甲状腺24 h摄131Ⅰ率、甲状腺质量、每克甲状腺组织131Ⅰ剂量、结节对疗效的影响有统计学意义(P值均＜0.05).结论 服用131Ⅰ后随访期内疗效较好,甲状腺质量、急躁、易惊、食欲亢进、心悸等症状和体征明显改善.对于年龄偏大、甲状腺24h摄131Ⅰ率高、甲状腺质量大、甲状腺有结节的患者,疗效较差,应适当增加服131Ⅰ剂量;反之,应减少.     

Zinc sulphate following the administration of iodine-131 on the regulation of thyroid function, in rats

Hyperthyroidism in men is often treated with high doses of iodine-131 ((131)I), which may induce radiation side effects to patients and their environment. These therapeutic doses of (131)I could be decreased, if the (131)I uptake of the thyroid gland of the patients could be increased. Zinc sulphate has been considered to exercise a protective role by maintaining the cellular integrity of the thyroid under various pathological states. The aim of our study was to study in Wistar rats whether zinc sulphate can after treatment of the thyroid gland with (131)I: a) increase the uptake of (131)I in the thyroid and b) stabilize the function of the follicular cells. If such a stabilization finally exists in men we could have favorable results like fewer cases of hypothyroidism after (131)I treatment of hyperthyroidism. To carry out these investigations, rats were divided into four groups comprising of eight animals each. Group I animals served as normal controls. Group II animals received a dose of 3.7 MBq of (131)I. Group III animals were supplemented with zinc (227 mg/L of drinking water) and animals in Group IV were given (131)I together with zinc sulphate as above. Our results showed that in Group II, serum levels of tetra-iodo-thyronine (T(4)) and tri-iodo-thyronine (T(3)) decreased significantly as a function of time following (131)I treatment. An increase in the levels of serum thyroid stimulating hormone (TSH) was noticed one week after (131)I treatment, becoming less pronounced with time. In Group II, thyroid uptake at 2h and at 24h was significantly decreased. In the same Group biological half life (T(biol)) of (131)I in the thyroid gland, was significantly elevated four weeks after the administration of (131)I and decreased eight weeks after. In Group IV animals, zinc sulfate after four weeks, induced normalization of elevated serum TSH levels and a further increase in the T(biol) of (131)I. After eight weeks in these animals, serum T(3) became normal and TSH remained at normal levels. Thyroid (131)I uptake at 2 and 24 h was increased as compared to Group II. Group III animals showed some increase in the levels of Na(+)K(+)ATPase and type 1,5'-deiodinase (5'-DI) as compared to normal rats of Group I. In conclusion, this study suggests the protective potential of zinc sulphate in the disturbed after (131)I treatment, thyroid function, thyroid hormones and TSH while the (131)I uptake was reduced. Thus, if this result is further confirmed, zinc sulphate may show to be a promising radioprotective agent for the thyroid gland.     

Relationship between cumulative radiation dose and salivary gland uptake associated with radioiodine therapy of thyroid cancer

AIM: To estimate the individual absorbed dose to the parotid and submandibular salivary glands in radioiodine therapy and its dependence from the previous cumulative therapy. METHODS: Fifty-five patients with differentiated thyroid carcinoma after thyroidectomy received 1-21 GBq (131)I using single activities of 1-6 GBq. The patients were stratified according to the cumulative activities into low-activity (1-2 GBq), middle-activity (3-7 GBq), and high-activity groups (9-21 GBq). The time-activity curves over the respective salivary glands were derived from multiple static calibrated images measured for each patient up to 48 h after ingestion of the radioiodine therapy capsule with a gamma camera. Manually drawn regions of interests were used to determine the background activities and the activities arising from the salivary glands. The gland volumes were determined by ultrasonography using appropriate volume models. RESULTS: The median absorbed dose per administered activity of each single parotid and submandibular gland was about 0.15 Gy.GBq (range, 0.1-0.3 Gy.GBq(-1)) and 0.48 Gy.GBq(-1) (range, 0.2-1.2 Gy.GBq(-1)), respectively. The maximum uptake of both gland types was significantly lower for the high-activity than for the low-activity groups and correlated with the mean cumulative administered activity of the activity groups. CONCLUSION: The iodine uptake of salivary glands is significantly reduced, whereas the absorbed dose per administered (131)I activity was not significantly decreased during the course of therapy. Comparing the well-known dose-effect relationships in external radiation therapy, the absorbed dose per administered (131)I activity is too low to induce comparable radiation damage, suggesting an inhomogeneous distribution of (131)I in human salivary glands.     

The effect of gadolinium contrast media on radioiodine uptake by the thyroid gland

OBJECTIVE: Patients with thyroid cancer may require detailed anatomic imaging before 131I therapy. Imaging by contrast-enhanced CT is contraindicated because it may result in saturation of tissues with iodine, decreasing the avidity of thyroid or thyroid cancer cells to subsequent radioiodine for extended intervals. Gadolinium-enhanced MRI offers an alternative to CT for detailed anatomic imaging. However, it is not known whether gadolinium contrast affects uptake of iodine by the thyroid gland since lanthanides affect ion transport in a variety of ways. The objective of this project was to determine whether the gadolinium MRI contrast injection alters thyroid uptake of radioiodine. METHODS: Radioiodine uptake by the thyroid gland was measured at 6 h and 24 h after the oral administration of 100 microCi 123I-Na-I. Three to seven days later, a standard dose (20 mL) of Magnevist (gadolinium DTPA) was administered intravenously. Another capsule of 100 microCi 123I Na-I immediately was given orally, and 6-h and 24-h radioiodine uptake by the thyroid gland was again measured and compared to baseline values. RESULTS: There was no statistically significant difference in uptake of radioiodine uptake by the thyroid gland between baseline values and those acquired immediately after the administration of Magnevist. CONCLUSION: Contrast-enhanced MRI may be safely performed before contemplated determinations of thyroid uptake of radioiodine, 131I therapy for hyperthyroidism, and postsurgical 131I imaging and therapy for well-differentiated thyroid cancer.     

A study of the possibility of curing Graves' disease based on the desired reduction of thyroid mass (volume) as a consequence of 131I therapy: a speculative paper

PURPOSE: The possibility of predicting the final volume of Graves' disease thyroids submitted to 131I therapy could allow the physician to decide what activity to administer based on the desired volume reduction instead of on a fixed value of the thyroid radiation absorbed dose. In this paper the relationship between maximum uptake of 131I, fractional reduction of thyroid volume and outcome of Graves' disease is discussed. METHODS: The results are based on ultrasonography thyroid volume measurements before administration of therapy and at the moment of recovery from Graves' disease (thyroid stimulating hormone >0.3 microIU x ml(-1) in the absence of anti-thyroid drug therapy) and on measurements of 131I uptake in 40 patients. It is shown that the possibility of curing Graves' disease may be individually related to the final volume of the patient's thyroid. An equation is presented to calculate the 'optimal' final thyroid volume. RESULTS: A comparison between the traditional method, based on absorbed dose, and the final method, based on volume, has been carried out retrospectively. In the first case a median activity of 529 MBq has been administered; in the second, a median activity of 394 MBq (non-parametric Wilcoxon test, P<0.05) should be administered. The corresponding thyroid median absorbed doses are, respectively, 353 Gy and 320 Gy (non-parametric Wilcoxon test, P<0.02). CONCLUSION: A method to evaluate individually the 'optimal' final thyroid mass is presented and discussed. The method based on 'volume reduction' could probably reduce the activity and the thyroid absorbed dose compared to the method based on 'empirical' calculations, thus allowing the administration of 131I therapy to be optimized.     

Does thyroid stunning exist? A model with benign thyroid disease

With regard to the treatment of differentiated non-medullary thyroid carcinoma, there is controversy over whether radiation from a diagnostic radioiodine (131I) application really does have a suppressive effect on the uptake of subsequent therapeutic 131I (so-called thyroid stunning). However, inherent difficulties in exact remnant/metastatic tissue volumetry make it difficult to quantify how much diagnostic 131I is actually absorbed (absorbed energy dose) and hence to decide whether a threshold absorbed dose exists beyond which such stunning would occur. Since in benign thyroid disease the target volume can be readily quantified by ultrasonography, we sought to determine definitely whether stunning of thyroid cells occurs upon a second application of radioiodine 4 days following the first one. We therefore studied 171 consecutive patients with benign thyroid disease (diffuse goitre, Graves' disease, toxic nodular goitre) who received two-step 131I therapy during a single in-patient stay. For application of both calculated 131I activities we performed kinetic dosimetry of 131I uptake, effective half-life and absorbed dose. At the second application, patients showed significant stunning (a 31.7% decrease in 131I uptake, from 34.7% +/- 15.4% at first application to 23.7% +/- 12.3% at second application, P < 0.0005) without a significant difference in effective half-life (4.9 +/- 1.3 vs 5.0 +/- 1.7 days, P > 0.2). ANOVA showed that the extent of stunning was influenced significantly only by the absorbed energy dose at first application (F = 13.5, P < 0.0005), while first-application 131I activity, target volume, gender and thyroid function had no influence (all F < or = 0.71, all P > 0.4). There was no significant correlation between extent of thyroid stunning and first-application 131I activity ( r = 0.07, P > 0.3), whereas there was a highly significant correlation between thyroid stunning and first absorbed energy dose (r = 0.64, P < 0.00005), the latter correlation fitting a logarithmic model best. Multivariate factor analysis also revealed first absorbed energy dose to be the only decisive stunning factor. In conclusion, our study confirms that stunning exists in benign thyroid conditions and that it is a purely radiobiological inhibitory phenomenon related to absorbed dose.     

131I清除分化型甲状腺癌术后残留腺体的内照射吸收剂量与疗效的分析

目的 探讨131I清除DTC术后残留甲状腺组织（简称清甲）的内照射吸收剂量与疗效的相关性.方法 前瞻性分析2009年9月至2011年9月拟行清甲的72例DTC患者[男14例,女58例,年龄16～67（41±16）岁].在患者服用3.7 GBq 131I后采用连续显像法评估残留腺体的碘代动力学,利用超声测量残留腺体的质量,按照美国核医学会医用内照射剂量学委员会提出的内照射吸收剂量计算方法,计算残留腺体的吸收剂量.清甲治疗后6～9个月,判断疗效：若刺激状态下Tg＜l μg/L及颈部超声检查提示甲状腺床区无腺体组织残留,判断为清甲成功.清甲成功与未成功者组间比较采用两样本t检验.结果 72例患者的残留腺体24h摄碘率为0.9％～6.3％, 131I有效半衰期为12.0～146.4 h,腺体质量为1.0～6.9g,吸收剂量为23～2 197 Gy,24 h吸收剂量率为0.5～8.1 Gy/h.43例清甲成功者与29例清甲未成功者残留腺体的吸收剂量分别为（363±148） Gy和（341±167） Gy,差异无统计学意义（￡=15.097,P＞0.05）;24 h吸收剂量率分别为（3.7±2.1） Gy/h和（2.9±1.6） Gy/h,差异有统计学意义（t=7.908,P＜0.05）.结论 131I清甲残留腺体的吸收剂量率影响清甲疗效.     

甲状腺乳头状癌患者术后首次131I治疗后辐射剂量率的影响因素及出院时间的探讨

目的 探讨甲状腺乳头状癌(PTC)患者术后首次131I治疗后影响辐射剂量率降低的相关因素,并预估其住院隔离时间。方法 选取2015年5月至2018年11月于南方医科大学珠江医院住院并首次行131I治疗的PTC患者167例,其中男性43例、女性124例,年龄(37.14± 12.00)岁。将所有患者按治疗剂量分为高剂量组(63例)和低剂量组(104例),于治疗后24、48、72、96 h时测量距离患者1 m处的辐射剂量率,将治疗后患者体内滞留131I活度为400 MBq时的时间点定为出院时间。采用多重线性回归方法分析影响辐射剂量率降低的相关因素。组间比较采用两独立样本非参数检验或两独立样本t检验。结果 PTC患者首次行131I治疗后的辐射剂量率随时间推移迅速下降,高剂量组治疗后的24、48 h辐射剂量率[(70.62±34.45)、15.64 μSv/h]明显高于低剂量组[(11.27±5.13)、2.03 μSv/h],且差异均有统计学意义(t=-13.581、-7.952,均P <0.01)。81.0%(51/63)和90.5%(57/63)的高剂量组患者分别可在治疗48 h和72 h后出院,99%(103/104)的低剂量组患者可在治疗24 h后出院。多重线性回归分析显示,131I剂量和2 h摄碘率对高剂量组24 h辐射剂量率的影响有统计学意义(F=9.23,复相关系数R2=0.212,P<0.01),高剂量组24 h辐射剂量率与2 h摄碘率和131I剂量呈正相关;性别、24 h摄碘率和残甲法3对高剂量组48 h辐射剂量率的影响有统计学意义(F=34.45,复相关系数R2=0.622,P<0.01),48 h辐射剂量率与24 h摄碘率和残留甲状腺体积呈正相关,与性别呈负相关;131I剂量和24 h饮水量对低剂量组24 h辐射剂量率的影响有统计学意义(F=12.76,复相关系数R2=0.186 ,P<0.01),低剂量组24 h辐射剂量率与131I剂量呈正相关,与24 h饮水量呈负相关。结论 PTC术后患者首次131I治疗24 h后,影响其辐射剂量率降低的主要因素是服用131I的剂量,而48 h后的主要影响因素是24 h甲状腺摄碘率、残留甲状腺体积和性别。低剂量组和高剂量组平均住院时间分别为1 d和2 d左右。     

The absorbed dose to the blood is a better predictor of ablation success than the administered <Superscript>131</Superscript>I activity in thyroid cancer patients

Purpose  

The residence time of ¹³¹I in the blood is likely to be a measure of the amount of ¹³¹I that is available for uptake by thyroid remnant tissue and thus the radiation absorbed dose to the target tissue in ¹³¹I ablation of patients with differentiated thyroid cancer (DTC). This hypothesis was tested in an investigation on the dependence of the success rate of radioiodine remnant ablation on the radiation absorbed dose to the blood (BD) as a surrogate for the amount of ¹³¹I available for iodine-avid tissue uptake.     

Whole-body (131)I washout in a patient with metastatic well-differentiated papillary thyroid carcinoma treated with repeated (131)I administration

We describe the case of a 37-year-old male patient suffering from papillary carcinoma of the thyroid gland with pulmonary metastases who after total thyroidectomy on 29/07/1998 was submitted to three treatments with high doses of (131)I and studied as to the whole body clearance of (131)I by measuring the dose rate of (131)I. The patient was referred to us for total ablation of post surgery remnant of thyroid tissue on 19/09/1998. Due to lymphadenic metastases and high Tg values: 450 ng/ml, he was purposely given therapeutically a high dose of 5146 MBq (131)I. On the whole body post-operative scintiscan that followed, a diffuse uptake of (131)I in the lungs and in the thyroid remnant was found. The patient was given 7307 MBq (131)I after 7 months and 5154 MBq of (131)I after another 10 months, because Tg was increased. Whole body scintiscan after the third treatment as mentioned above, showed poor uptake of (131)I in the thyroid gland area and in the lungs. No side effects were noticed, Tg fell to 4.5-7 ng/ml and the patient was in good condition with no abnormal findings on the X-rays or CT of the thorax. After iodine administration whole body measurements of the dose rate of the clearance of (131)I measured by an ionization chamber at a distance of 2 m from the thorax, were performed. For the first treatment effective half-lives of (131)I of the patient, as measured for the two components of the clearance curve, were 4.4 h and 16.8 h respectively. For the second and third treatment clearance curve had only one component and effective half-lives were 22.5 h and 11 h respectively. Remaining activity of (131)I at 48 h was for the first, second and third treatment: 13.3% (685 MBq), 22.8% (1670 MBq) and 4.2% (222 MBq) respectively. We do not know any similar case in the literature with whole body measurements of (131)I clearance in patients undergoing repeated (131)I treatment as above, especially with diffuse pulmonary uptake of (131)I indicating metastatic lesions after the first treatment of (131)I post total thyroidectomy. The interest of the above case also lies on the fact that there were three successive treatments with (131)I and three whole body (131)I measurements. Clearance rate indicated the need for additional treatment and the treatment followed was successful.     

Does thyroid stunning exist? A model with benign thyroid disease

With regard to the treatment of differentiated non-medullary thyroid carcinoma, there is controversy over whether radiation from a diagnostic radioiodine (¹³¹I) application really does have a suppressive effect on the uptake of subsequent therapeutic ¹³¹I (so-called thyroid stunning). However, inherent difficulties in exact remnant/metastatic tissue volumetry make it difficult to quantify how much diagnostic ¹³¹I is actually absorbed (absorbed energy dose) and hence to decide whether a threshold absorbed dose exists beyond which such stunning would occur. Since in benign thyroid disease the target volume can be readily quantified by ultrasonography, we sought to determine definitely whether stunning of thyroid cells occurs upon a second application of radioiodine 4 days following the first one. We therefore studied 171 consecutive patients with benign thyroid disease (diffuse goitre, Graves' disease, toxic nodular goitre) who received two-step ¹³¹I therapy during a single in-patient stay. For application of both calculated ¹³¹I activities we performed kinetic dosimetry of ¹³¹I uptake, effective half-life and absorbed dose. At the second application, patients showed significant stunning (a 31.7% decrease in ¹³¹I uptake, from 34.7%ᆣ.4% at first application to 23.7%ᆠ.3% at second application, P<0.0005) without a significant difference in effective half-life (4.9ǃ.3 vs 5.0ǃ.7 days, P>0.2). ANOVA showed that the extent of stunning was influenced significantly only by the absorbed energy dose at first application (F=13.5, P<0.0005), while first-application ¹³¹I activity, target volume, gender and thyroid function had no influence (all FА.71, all P>0.4). There was no significant correlation between extent of thyroid stunning and first-application ¹³¹I activity (r=0.07, P>0.3), whereas there was a highly significant correlation between thyroid stunning and first absorbed energy dose (r=0.64, P<0.00005), the latter correlation fitting a logarithmic model best. Multivariate factor analysis also revealed first absorbed energy dose to be the only decisive stunning factor. In conclusion, our study confirms that stunning exists in benign thyroid conditions and that it is a purely radiobiological inhibitory phenomenon related to absorbed dose.     

Impact of radiocontaminants in commercially available iodine-123: dosimetric evaluation

Iodine-123 (123I) is considered by some to be the radionuclide of choice for thyroid scintigraphy because of its ideal physical and biological characteristics and low radiation absorbed dose to the thyroid. However, commercially available 123I (p,2n) and (p,5n) have radiocontaminants. The MIRD formalism was used to estimate the absorbed dose to the thyroid for various age groups receiving recommended administered activities at the time of delivery and at two half-lives assuming radiocontamination levels specified by the suppliers. The calculations demonstrate that an 131I uptake with a technetium-99m scan at the time of delivery results in less absorbed dose to the thyroid than an 123I (p,2n) scan and uptake. At two half-lives the absorbed dose triples and becomes equivalent to the dose from an 131I scan. The absorbed dose from an 123I (p,5n) scan at two half-lives is higher than that of an 123I (p,2n) scan at the time of delivery. Iodine-123 capsules should not be decayed down in order to obtain a recommended pediatric administered activity. There appears to be no dosimetric advantage of commercially available 123I for thyroid scintigraphy for adults or most children.     

Iodide kinetics and dosimetry in vivo after transfer of the human sodium iodide symporter gene in rat thyroid carcinoma cells.

Transfer of the human sodium iodide symporter (hNIS) has been proposed as a new principle of cancer gene therapy. This study evaluates the iodide kinetics and dosimetry of iodide in hNIS-expressing thyroid carcinoma cells under optimized conditions. METHODS: Using a bicistronic retroviral vector for the transfer of the hNIS and the hygromycin resistance gene, hNIS-expressing rat thyroid carcinoma cell lines were generated. Afterward, Na(125)I uptake and efflux were determined in genetically modified and wild-type cells in the presence or absence of modulators of iodide transport. In addition, the (131)I distribution in thyroid-ablated nude mice bearing wild-type and genetically modified thyroid carcinomas was monitored after intraperitoneal administration of (131)I with and without coadministration of lithium carbonate. RESULTS: hNIS-expressing cell lines accumulated up to 49 times more iodide than did noninfected cells, with a maximal iodide uptake after 30 min of incubation. However, a 90% efflux of the radioactivity occurred 20 min after replacement of the medium. In mice, the hNIS-expressing tumors accumulated up to 23 and 19.5 times more iodide than did the wild-type tumors in lithium-treated and control animals, respectively. However, efflux of the radioactivity was also observed in vivo: After 24 h, hNIS-expressing tumors lost 82.5% and 80.4% of the initial activity. Dosimetric calculations showed that 1,650 MBq of (131)I per square meter resulted in 5.4 and 5.2 Gy in hNIS-expressing tumors and 0.24 and 0.26 in wild-type tumors. CONCLUSION: Transduction of the hNIS gene in rat thyroid carcinoma cells induces iodide transport, which is associated with rapid efflux. Application of (131)I in clinically relevant amounts did not result in therapeutically useful absorbed doses in hNIS-expressing tumors in vivo, even under optimized conditions of thyroid ablation and treatment with lithium carbonate.     

^131I-美妥昔单抗联合动脉内化疗栓塞治疗原发性肝癌的内照射吸收剂量估算

目的对^131I-美妥昔单克隆抗体（简称单抗）联合动脉内化疗栓塞（TACE）治疗原发性肝癌患者器官的内照射吸收剂量进行估算。方法21例患者肝动脉内按体质量注入^131I-美妥昔单抗（27．75MBq／kg）和混合化疗药物的碘化油乳剂。用1计数仪测量5min和0．5,2,4,24,48,72,120,168h血样和尿样的放射性。用SPECT仪行4或5次全身扫描。用感兴趣区图像处理法计算主要器官和全身放射性活度占给予放射性活度的百分数（％ID）,SPSS12．0软件拟合时间-％ID曲线,计算累积活度,依据医学内照射辐射剂量学（MIRD）方法和血液间接法计算器官和红骨髓的内照射吸收剂量,计算肿瘤／非肿瘤放射性比值。结果^131I-美妥昔单抗的平均剂量为1．89（1．47～223）GBq／次。显像示放射性主要浓聚于肝区肿瘤组织,随时间延长,甲状腺后期有放射性浓聚,体内其他组织未见明显放射性分布。器官吸收剂量（12例）：肝（3．19±1．01）Gy,脾（3．65±2．41）Gy,甲状腺（3．61±2．40）Gy,肺（0．97±0．23）Gy,肾（0．96±0．35）Gy,全身（0．57±1．55）Gy,红骨髓（0．55±0．09）Gy（7例）。肿瘤／肝放射陛比值（7例）：3h为2．88±1．11,64h为2．15±0．53,120h为1．81±0．39,168h为1．64±0．39。结论依据MIRD方法计算获得了主要器官、红骨髓和全身内照射吸收剂量,这对更好评价疗效、不良反应和制订个体化方案有重要意义。     

Iodine-131 uptake and turnover rate vary over short intervals in Graves' disease

From a Dutch questionnaire, it was apparent that nearly all institutions used percentage of radioiodine uptake for calculation of the radioiodine dose in Graves' disease. Although there is a general belief that fluctuations in radioiodine uptake may occur, with few exceptions relatively long intervals were accepted between the uptake measurement and the actual therapy dose. With the aim of optimizing the pretherapeutic work-up, we evaluated the stability of iodine uptake over time in patients with Graves' disease who were referred for 131I therapy. 131I uptake was measured in 300 consecutive patients for the calculation of the required 131I therapy dose; data were complete for 291 patients (97%). After discontinuing thyroid medication for 3 days, standardized thyroid probe measurements were performed 5 and 24 h after ingestion of a capsule containing 0.37 MBq 131I-NaI. Measurements were performed at the time of scintigraphic diagnosis (test 1), as well as immediately before 131I therapy (test 2). The time interval between test 1 and test 2 ranged from 2 to 421 (median 40) days. A relative increase or decrease greater than 10% between tests 1 and 2 occurred in 180 of 291 cases (62%) at 5 h and in 158 of 291 patients (54%) at 24 h. These changes were not related to the interval between the tests or to initial uptake values, thyroid mass, gender or age. Rapid turnover of radioiodine (5 h/24 h uptake ratio > 1) was noted in 17% of the patients during test 1 and in 15% during test 2. Rapid turnover was persistent (present in both tests 1 and 2) in only 9%. We conclude that patients with Graves' disease show considerable changes in 131I uptake over relatively short periods of time, and the turnover rate of 131I in this condition is not constant.     

Self-stunning in thyroid ablation: evidence from comparative studies of diagnostic 131I and 123I

Twenty-six patients who had undergone recent surgery for differentiated thyroid cancer were investigated using iodine-131 iodide (120 MBq). Uptake in the thyroid bed was measured at 3 days using a dual-head gamma camera. An ablation activity of 131I iodide (4,000 MBq) was administered 3-38 (median 14) days later and uptake in the thyroid bed measured once or twice, 1-3 days post therapy. For measurements post therapy, the gamma camera was operated in the high-count rate mode with appropriate correction factors to compensate for any count loss. A further 16 patients were given iodine-123 iodide (200 MBq) as the diagnostic agent and uptake was measured at 24 h. The ablation activity was administered 5-47 (median 19) days later and uptake again measured at 24 h. In some cases, a further measurement of uptake was made within the period 1-3 days post therapy. Reduced uptake of the therapeutic administration ( P<0.001) was observed in all 26 patients given diagnostic 131I, with a median value of 32.8% (range 6%-93%) of the uptake in the diagnostic study. In the patients given diagnostic 123I, reduced uptake of the ablative radioiodine was observed in 15 of the 16 patients ( P<0.001), and overall the median value was 58.8% (range 17%-130%) of the diagnostic uptake. In one case the uptake post therapy was increased. The stunning observed in the group given 123I was significantly less ( P<0.001) than in the group given 131I. In the patients given diagnostic 131I, stunning appeared to increase in severity the longer the time interval between the diagnostic and therapeutic radionuclides, for intervals up to 25 days. Thereafter, there seemed to be some recovery of uptake capability. Overall there was no evidence of a large rapid loss of radionuclide from the thyroid bed 1-3 days post therapy. The stunning observed using 123I could not be explained by errors in the estimation of relative uptake due to different tissue absorption of the 131I and 123I photons, nor by the radiation dose delivered by the 123I. However, the ablative 131I itself may cause stunning because the cumulated activity, over the first few hours of uptake, is not insignificant when compared with all the cumulated activity from a diagnostic administration of 131I. The resultant radiation dose to the thyroid remnant, as the therapeutic radioiodine is being taken up, may be sufficient to inhibit the uptake process, thus leading to a reduction in maximum uptake when compared with that of a diagnostic activity of radioiodine.     

Reduced iodide transport (stunning) and DNA synthesis in thyrocytes exposed to low absorbed doses from 131I in vitro.

Thyroid stunning refers to reduced uptake of (131)I in the thyroid tissue (or tumor) during radioiodine ((131)I) therapy compared with the uptake measured after the previous administration of (131)I for diagnostic purposes. The phenomenon is clinically important, as it can potentially lead to the undertreatment of thyroid cancer or to unnecessarily high absorbed doses in critical organs. Previous clinical and experimental studies indicated that thyroid stunning is absorbed dose dependent. The aim of this study was to investigate the effects of (131)I irradiation on (125)I(-) transport and cell proliferation at low absorbed doses in vitro. METHODS: Primary cultured porcine thyroid cells were grown to form a confluent monolayer of epithelial cells on a filter in a bicameral culture system. The cells were continuously irradiated with (131)I in the culture medium for 48 h to obtain 0.0015-1.5 Gy. At 3 d after irradiation was stopped, the transepithelial iodide transport capacity was evaluated by measuring (125)I(-) transport from the basal chamber compartment to the apical chamber compartment. The effect of (131)I irradiation on DNA synthesis was estimated by pulse labeling with (3)H-thymidine of both subconfluent and confluent cells irradiated with up to 9 Gy. Total DNA content was measured to quantify cell numbers. RESULTS: A statistically significant reduction in (125)I(-) transport was seen at absorbed doses of >or=0.15 Gy, with a 50% reduction at 1.5 Gy, compared with the results observed for nonirradiated control cells. (3)H-Thymidine incorporation was already statistically significantly reduced at absorbed doses of 0.01-0.1 Gy, but 0.15-0.3 Gy did not affect DNA synthesis. However, absorbed doses of >or=1 Gy again resulted in reduced DNA synthesis. A 50% reduction was obtained at 4 Gy. Total DNA measurements revealed a statistically significant reduction in cell numbers at 8 Gy. CONCLUSION: The lowest absorbed dose from (131)I that reduced iodide transport was 0.15 Gy. Because stunning was found at low absorbed doses, it might occur for (131)I treatment not only of thyroid cancer but also of thyrotoxicosis. On the basis of differences in dose responses, radiation-induced thyroid stunning and cell cycle arrest may be independent phenomena.     

Radiopharmacokinetics and radiation absorbed dose calculations from 131I-meta-iodobenzylguanidine (131I-MIBG)

In connection with clinical 131I-MIBG studies of patients with suspected pheochromocytoma and adrenomedullary hyperplasia quantitative biokinetic data have been collected in order to improve the present estimations of absorbed dose to various organs and tissues. Whole-body profiles as a function of time were measured with a whole-body counter. The retention in the total body and in the thyroid gland could be derived from the measured whole-body profiles by summing up the corresponding values. The retention of 131I-MIBG could not be exactly measured for further organs from the whole-body profiles in man. For this reason animal studies were performed with mice. The biokinetic animal data were transferred to man in form of the cumulative activity for the various organs. The mean absorbed dose for selected organs per injected activity unit was calculated using the concept of absorbed fractions (MIRD method) taking into account the radioactivity within the remaining body. Except for both the adrenal medulla and the thyroid gland the absorbed doses for all the other selected organs are in a range from 0.108 mGy MBq-1 for the testes to 0.176 mGy MBq-1 for the lungs. The absorbed dose to the thyroid gland amounts to the considerable value of 5.69 mGy MBq-1 although the thyroid gland was blocked. The greatest absorbed dose was estimated for the normal adrenal medulla with 18.67 mGy MBq-1.