Procedure guideline for iodine-131 whole-body scintigraphy for differentiated thyroid cancer (version 3)

Version 3 of the procedure guideline for (131)I whole-body scintigraphy (WBS) is the counterpart to the procedure guideline for radioiodine therapy (version 3) and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. (131)I WBS 3-6 months after (131)I ablation remains a standard procedure in an endemic area for thyroid nodules and the high frequency of subtotal surgical procedures. Follow-up without (131)I WBS is only justified if the following preconditions are fulfilled: low-risk group pT1-2, pN0 M0 with histopathologically confirmed pN0, (131)I uptake <2%, (131)I WBS during ablation without any suspicious lesion, stimulated thyroglobulin (Tg)-level 3-6 months after ablation <2 ng/mL, and absence of anti-thyroglobulin-antibodies with normal recovery-testing. If patients from the low-risk group show normal (131)I WBS 3-6 months after ablation and stimulated Tg is of <2 ng/mL, there will be no need for additional routine (131)I WBS. If patients from the high-risk group show normal (131)I WBS and stimulated Tg-level of <2 ng/mL 3-6 months after ablation, the follow-up care should include repeated stimulated Tg-measurements. If the Tg-level remains below 2 ng/mL, an additional (131)I WBS will be not necessary. The recommended intervals for stimulated Tg-testing are adapted to the prior intervals for (131)I WBS-testing in the high-risk group. Increased anti-thyroglobulin-antibodies or incomplete recovery-testing make an individual strategy of follow-up care necessary, which include (131)I WBS.     

131I治疗分化型甲状腺癌指南(2021版)

近几年有关分化型甲状腺癌(differentiated thyroid cancer,DTC)术后¹³¹I治疗理念、治疗手段、随访监测及评估体系不断更新,针对我国DTC的发病及诊治现状,中华医学会核医学分会组织专家委员会对《¹³¹I治疗分化型甲状腺癌指南(2014版)》进行了修订,制定了《¹³¹I治疗分化型甲状腺癌指南(2021版)》,以期进一步规范和指导我国¹³¹I治疗DTC的临床诊治行为。本指南的推荐级别见表1,证据强度分级见表2.     

Guidelines for radioiodine therapy of differentiated thyroid cancer

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 community on how to ablate thyroid remnant or treat inoperable advanced DTC or both employing large 131-iodine (¹³¹I) activities. Discussion  For this purpose, recommendations have been formulated based on recent literature and expert opinion regarding the rationale, indications and contraindications for these procedures, as well as the radioiodine activities and the administration and patient preparation techniques to be used. Recommendations also are provided on pre-RAIT history and examinations, patient counselling and precautions that should be associated with ¹³¹I iodine ablation and treatment. Furthermore, potential side effects of radioiodine therapy and alternate or additional treatments to this modality are reviewed. Appendices furnish information on dosimetry and post-therapy scintigraphy.     

Guideline for radioiodine therapy for benign thyroid diseases (version 3)

The version 3 of the guideline for radioiodine therapy for benign thyroid diseases presents first of all a revision of the version 2. The chapter indication for radioiodine therapy, surgical treatment or antithyroid drugs bases on an interdisciplinary consensus. The manifold criteria for decision making consider the entity of thyroid disease (autonomy, Graves' disease, goitre, goitre recurrence), the thyroid volume, suspicion of malignancy, cystic nodules, risk of surgery and co-morbidity, history of subtotal thyroidectomy, persistent or recurrent thyrotoxicosis caused by Graves' disease including known risk factors for relapse, compression of the trachea caused by goitre, requirement of direct therapeutic effect as well as the patient's preference. Because often some of these criteria are relevant, the guideline offers the necessary flexibility for individual decisions. Further topics are patients' preparation, counseling, dosage concepts, procedural details, results, side effects and follow-up care. The prophylactic use of glucocorticoids during radioiodine therapy in patients without preexisting ophthalmopathy as well as dosage and duration of glucocorticoid medication in patients with preexisting ophthalmopathy need to be clarified in further studies. The pragmatic recommendations for the combined use of radioiodine and glucocorticoids remained unchanged in the 3rd version.     

Procedure guideline for iodine-131 whole-body scintigraphy for differentiated thyroid cancer (version 2)

The version 2 of the procedure guideline for iodine-131 whole-body scintigraphy for differentiated thyroid cancer is an update of the procedure guideline published in 1999. The following statements are added or modified: The two alternatives of an endogenous TSH-stimulation by the withdrawal of the thyroidal hormone medication and of an exogenous TSH-stimulation by the injection of the recombinant human TSH (rhTSH) have an equal sensitivity for the diagnostic use of radioiodine and for the measurement of thyroglobulin. Image acquisition under rhTSH is obtained approximately 48 h after the radioiodine administration, while an interval of about 72 h is preferred under endogenous TSH-stimulation. If iodine-negative metastases are expected, the feasibility of scintigraphy using (99m)Tc sestamibi or preferably positron emission tomography using (18)F-fluorodeoxyglucose should be considered. The sensitivity of FDG-PET is increased by TSH-stimulation. Before planning the iodine-131 scintigraphy the patient has to avoid iodine-containing medication and the possibility of additives of iodine in vitamin- and electrolyte-supplementation has to be considered.     

Procedure guideline for thyroid scintigraphy (version 3)

The version 3 of the procedure guideline for thyroid scintigraphy is an update of the procedure guideline previously published in 2003. The interpretation of the scintigraphy requires the knowledge of the patients' history, the palpation of the neck, the laboratory parameters and of the sonography. The interpretation of the technetium-99m uptake requires the knowledge of the TSH-level. As a consequence of the improved alimentary iodine supply the (99m)Tc-uptake has decreased; 100,000 counts per scintigraphy should be acquired. For this, an imaging time of 10 minutes is generally needed using a high resolution collimator for thyroid imaging.     

Procedure guideline for radioiodine test (version 2)

The version 2 of the procedure guideline for radioiodine test is an update of the guideline published in 1999. The following statements were added or modified: 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 iodide crystal, alternative 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 iodide in vitamin- or electrolyte-supplementation has to be considered.     

Procedure guideline for radioiodine therapy and 131iodine whole-body scintigraphy in paediatric patients with differentiated thyroid cancer

The procedure guideline for radioiodine ((131)I) therapy and (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 (131)I activity depends on the children's body weight. Radioiodine ablation in children with small papillary cancer (< or =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 (131)I ablation, the (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.     

Low-dose radioiodine therapy for patients with intermediate- to high-risk differentiated thyroid cancer

Annals of Nuclear Medicine - The efficacy of low-dose radioiodine therapy (RIT) for intermediate-risk or high-risk differentiated thyroid cancer (DTC) patients is controversial. Because of the...     

碘难治性分化型甲状腺癌的精准靶向治疗进展

甲状腺癌的发病率逐年上升,传统的治疗方法对于碘难治性分化型甲状腺癌的疗效有限。靶向治疗是近年来比较热门的新型治疗方法,在甲状腺癌的治疗上已取得一定研究成果。笔者就碘难治性分化型甲状腺癌的精准靶向治疗策略——药物靶向治疗、肽受体核素靶向治疗、局部精准治疗以及免疫治疗进行综述。     

Optimized 124I PET dosimetry protocol for radioiodine therapy of differentiated thyroid cancer.

Iodine kinetics and lesion dose per administered 131I activity (LDpA) of differentiated thyroid cancer metastases were determined using 124I PET. These data were analyzed to derive an optimized dosimetry protocol. METHODS: We evaluated the time-activity-concentration curves of 37 lesions in 17 patients who had undergone thyroidectomies. LDpA determination involved 124I PET images acquired at 4, 24, 48, 72, and 96 h after intake of a capsule containing 20-40 MBq of 124I. A combination of a linear and a monoexponential or a monoexponential function only parameterized the time-activity-concentration curves. The LDpAs, calculated using data from all 5 PET time points, served as reference. The lesions were classified into 3 groups, according to potential for cure with 131I therapy: low (< or =5 Gy GBq(-1); n = 14), medium (between 5 and 10 Gy GBq(-1); n = 9), or high LDpAs (>10 Gy GBq(-1); n = 14). Using the reference approach, the differences in the empiric kinetic parameters within the LDpA groups were evaluated. The reference LDpAs were compared with those derived from only 2, 3, or 4 PET data points and from 1 adapted 2-point approach. Lin's concordance correlation coefficient (rho c) and the mean absolute percentage deviation in LDpAs were used to assess agreement between simplified and reference approaches. RESULTS: The effective 124I half-life, linear activity-concentration rate (alpha), and 24-h activity concentration (CpA) (the latter 2 per administered 124I activity) differed significantly among the LDpA groups (P < 0.05). LDpAs correlated with 24-h CpAs (r = 0.94, P < 0.001). Using the 4-, 24-, and 96-h measurements, a rho c value of greater than or equal to 0.90 was found, and the mean absolute percentage deviation was less than or equal to 16%. Similar statistical values were obtained for the adapted approach, which was based on 24- and 96-h PET data points only. CONCLUSION: Lesion classification into LDpA groups was feasible using a single PET scan at approximately 24 h. Because of the highly variable kinetics, 1 additional measurement at approximately 96 h was needed to obtain a sufficiently reliable LDpA estimate. The adapted 24-96-h approach appears to be the optimal 124I protocol and is a reliable simplification of the 5-point protocol.     

Respiratory distress caused by radioiodine therapy in patients with differentiated thyroid cancer

Respiratory distress accompanied by stridor is an uncommon complication of 131I radioiodine therapy for differentiated thyroid cancer that occurs within 48 hours of treatment. This report presents three cases with papillary thyroid carcinoma in which 131I therapy caused this acute complication. One of them had no apparent risk for this complication such as the existence of remnant thyroid tissue or laryngeal problems before the treatment. These cases remind physicians that 131I therapy is not a simple, riskless procedure.     

Results of radioiodine therapy in patients with pulmonary metastases of differentiated thyroid cancer

Factors affecting the effect of 131I treatment and survival after pulmonary metastases in patients with differentiated thyroid cancer, were studied. Between 1984-1999, pulmonary metastases was observed in 51 out of 153 patients with differentiated thyroid cancer at our institution. Of these 41 patients had papillary and 10 follicular thyroid cancer. There were 37 females and 14 males with mean age (+/- S.D.) of 50.5 +/- 19.0 years. These 51 patients were subjected to 131I therapy. The effect of 131I treatment and the prognostic values of the following variables were examined: sex, age at the time of 131I treatment, histologic type of cancer, size of pulmonary metastases on CT, total-body scintigraphy with 201Tl and 131I, serum thyroglobulin levels and presence of metastases in distant sites other than lung. The effect of 131I treatment was evaluated by means of changes in the number and size of metastatic shadows on chest CT and by serum thyroglobulin levels. The minimum duration of follow-up was 12 months. Therapeutic 131I dose scans revealed detectable uptake in 25 of 51 patients. Therapeutic 131I dose uptake was achieved more frequently in patients under 40 years of age and in those with follicular cancers. Of the 51 patients, 13 were evaluated to be treated successfully. Those under 40 years of age, with 131I uptake in the lung and presence of other metastases showed a good response to treatment than others. Follicular cancer showed a more significant association with coarse type of lung metastases (> 5 mm in diameter on chest CT) and good 131I uptake than papillary cancer. Of all the variables studied, the best prognosis for survival was demonstrated by increased 131I uptake in pulmonary metastases. These results indicate that age, 131I uptake and presence of other metastases are important factors in predicting the effect of 131I treatment for pulmonary metastases of differentiated thyroid cancer.     

Procedure guideline for thyroid scintigraphy (version 2)

The version 2 of the procedure guideline for thyroid scintigraphy is an update of the procedure guideline published in 1999. The procedure guideline considers the current amendment of legislative rules (Richtlinie Strahlenschutz in der Medizin 2002). Indication and use of radiopharmaceuticals have to be confirmed by the specialist in nuclear medicine. Activities of 75 MBq technetium-99m, respectively of 10 MBq iodine-123 should not be exceeded without an individual justification. The interpretation of the scintigraphy requires the knowledge of the patients' history, the palpation of the neck, the laboratory parameters, and of the sonography. The interpretation of the technetium-99m uptake requires the knowledge of TSH concentration.     

A dose-effect correlation for radioiodine ablation in differentiated thyroid cancer

Purpose

The aim of this study was to determine the range of absorbed doses delivered to thyroid remnants, blood, and red marrow from fixed administrations of radioiodine and to ascertain whether the success of ablation is more dependent on these absorbed doses than on the administered activity.

Methods

Twenty-three patients received 3,000 MBq radioiodine following near-total thyroidectomy. The maximum absorbed dose to remnants was calculated from subsequent single photon emission tomography scans. Absorbed doses delivered to blood and red marrow were calculated from blood samples and from whole-body retention measurements. The protein bound iodine (PBI) was also calculated.

Results

Maximum absorbed doses to thyroid remnants ranged from 7 to 570 Gy. Eighteen of the 23 patients had a successful ablation. A significant difference was seen between the absorbed doses delivered to thyroid remnants, blood, and red marrow for those patients that had a successful ablation compared to those with a failed ablation (p?=?0.030, p?=?0.043 and p?=?0.048, respectively). The difference between the PBI values acquired at day 1 and day 6 were also indicative of response (p?=?0.074).

Conclusions

A successful ablation is strongly dependent on the absorbed dose to the thyroid remnant. Dosimetry-based personalized treatment can prevent both sub-optimal administrations, which entails further radioiodine therapy, and excessive administration of radioactivity, which increases the potential for radiation toxicity.     

Procedure guideline for radioiodine test (Version 3)

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.     

Cytokinesis-block micronucleus test in patients undergoing radioiodine therapy for differentiated thyroid carcinoma

Cytokinesis-blocked micronucleus assay (MNT) was applied in the peripheral blood lymphocytes of patients undergoing radioiodine-131 ((131)I) therapy for differentiated thyroid carcinoma (DTC) after thyroidectomy to assess the genotoxic risk of this therapy. The amount of administered (131)I activity varied from 3,330 to 4,030 MBq. Blood samples were taken immediately before (131)I administration and one month later, along with routine blood tests. Twenty-six patients underwent radioiodine ablation (RIA) or radioiodine therapy (RIT) after radical thyroidectomy. The aim of this therapy was to ablate residual thyroid tissue, to treat lymph node metastases and/or distant lung metastases. The amount of orally administered activity of (131)I ranged between 3,330 and 4,030 MBq according to the kind of therapy (RIA or RIT). In five patients the cytogenetic analysis was performed immediately before and one month after the second therapy which was given to them 6 months to 1 year after the first. Three patients were male and 23 female. The age of the patients ranged between 23 and 76 years (mean age: 48.6 years). Results show that after radioiodine therapy there is a significant increase in the frequency of micronuclei. Comparing the average frequency of micronuclei in the patients studied before and after (131)I, a more than doubling increase was found. Mean values +/- SD of the patients before and after (131)I therapy were 10.72 per thousand +/- 5.84 per thousandand 25.28 per thousand +/- 12.6 per thousand respectively. These findings indicate a genotoxic activity of (131)I therapy estimated after a period of one month.