The Effect of 131I Therapy on the Eradication of Helicobacter pylori in Patients with Thyroid Disorders: A Preliminary Study.

The leading cause of gastritis and its complications is Helicobacter pylori Radioactive iodine (131I) accumulates significantly in the stomach after consumption. On this basis, we decided to determine whether different doses of 131I in the stomach would be effective in eradicating the infection. Methods: All patients with hyperthyroidism or differentiated thyroid carcinoma who were referred for 131I treatment were invited to the study. A stool antigen test was conducted before consumption of 131I (0.15-5.5 GBq) and was repeated 2 mo later to detect H. pylori infection. Results: H. pylori positivity was found in 51.8% (14/27) of the patients. At 2 mo after treatment, 13 of the 14 patients with differentiated thyroid carcinoma or hyperthyroidism who had been identified as positive for H. pylori stool antigen before 131I administration were still positive, representing a nonsignificant eradication rate of 7.1%. Conclusion: Administration of 131I to patients with H. pylori did not show potential to eliminate the infection.

Predictive factors for the outcome of radioiodine therapy in patients with benign thyroid diseases.

PURPOSE: Radioiodine therapy (RIT) of benign thyroid diseases is an established therapy. This study aimed to identify factors predictive for outcome in patients with non-toxic goiter (NTG), unifocal (UFA), multifocal (MUFA) or diffuse autonomy (DISA) and Graves' disease (GD). METHODS: Retrospective analysis of 205 patients with benign thyroid disease (54 NTG, 46 MUFA, 24 DISA, 26 UFA, 55 GD) who underwent RIT. Follow up time was 12 months for determining treatment outcome. RESULTS: The type of disease was predictive for volume reduction after 12 months (NTS 66%, DISA 67%, MUFA 58%, UFA 51%, GD 71%, p<0.001) and post-treatment hypothyroidism (NTS 48%, DISA 33%, MUFA 15%, UFA 15%, p=0.006). Initial volume, intra-therapeutic uptake and intra-therapeutic half-life were independent prognostic factors for volume reduction 12 months after RIT. In patients with NTG, UFA, MUFA, DISA post-treatment hypothyroidism was significantly correlated with extent of volume reduction 12 months after RIT, achieved dose, higher pre-therapeutic TSH values and younger age. Two different strategies for pre-therapeutic dosimetry used in MUFA showed no differences regarding the therapeutic outcome. In GD, effective half-life, initial volume and Graves' ophthalmopathy were predictive for treatment failure. CONCLUSION: Reduction of thyroid volume and the percentage of hypothyroid patients one year after RIT was primarily dependent on the type of disease. In MUFA and DISA we could identify volume reduction after 3 months as a reliable predictor for hypothyroidism while in patients with GD a short intra-therapeutic half-life, a large pre-therapeutic volume and active Graves' ophtalmopathy were relevant predictors for treatment failure suggesting an intensified follow-up scheme in these patients.

[Guideline for Radioiodine Therapy for Benign Thyroid Diseases (6/2022 - AWMF No. 031-003)]. / DGN-Handlungsempfehlung (S1-Leitlinie): Radiojodtherapie bei benignen Schilddrüsenerkrankungen (Stand 6/2022 ­ AWMF-Registernummer: 031-003).

This version of the guideline for radioiodine therapy of benign thyroid disorders is an update of the version, which was published by the German Society of Nuclear Medicine (Deutsche Gesellschaft für Nuklearmedizin, DGN) in co-ordination with the German Society of Endocrinology (Deutsche Gesellschaft für Endokrinologie, DGE, Sektion Schilddrüse) and the German Society of General- and Visceral-Surgery (Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie, DGAV) in 2015. This guideline was harmonized with the recommendations of the European Association of Nuclear Medicine (EANM). According to the German "Directive on Radiation Protection in Medicine" the physician specialised in nuclear medicine ("Fachkunde in der Therapie mit offenen radioaktiven Stoffen") is responsible for the justification to treat with radioiodine. Therefore, relevant medical indications for radioiodine therapy and alternative therapeutic options are discussed within the guideline. This procedure guideline is developed in the consensus of an expert group. This fulfils the level S1 (first step) within the German classification of Clinical Practice Guidelines.

The EANM guideline on radioiodine therapy of benign thyroid disease.

This document provides the new EANM guideline on radioiodine therapy of benign thyroid disease. Its aim is to guide nuclear medicine physicians, endocrinologists, and practitioners in the selection of patients for radioiodine therapy. Its recommendations on patients' preparation, empiric and dosimetric therapeutic approaches, applied radioiodine activity, radiation protection requirements, and patients follow-up after administration of radioiodine therapy are extensively discussed.

[Radioiodine testing in clinical routine: Status in Germany 2021]. / Statuserfassung des Radiojodtests im klinischen Alltag in Deutschland 2021.

INTRODUCTION AND AIM: According to the German guideline on Radiation Protection in Medicine, the activity to be applied for radioiodine therapy of benign thyroid diseases is determined for each patient by means of the radioiodine test (RJT). The aim of this study is to record the different parameters of the RJT. MATERIAL AND METHODS: A web-based questionnaire was sent to all nuclear medicine departments in Germany via the DGN office. Parameters regarding tracer and activity, type of probe measurement, number and timing of measurements, use of fixed effective half-lives (eHWZ), calculation model and organ doses were requested. An assessment of continuous measurement of the thyroid iodine uptake over seven days by a wearable probe system was also requested. RESULTS: 38 of 94 facilities responded to the questionnaire. Major differences in RJT implementation were found concerning the parameters number and timing of measurements, probe-patient distance, use of fixed disease-specific eHWZ, and intended organ dose. Despite the DGN Guideline and DIN 6861-1, 74% of the facilities still use the simplified Marinelli formula from the DGN Recommendation of 1998. Only 8% have switched to the two-compartment model. 84% of the institutions expect that a wearable probe system could improve the calculation of the radioiodine activity necessary for treatment, but only 57% expect an improvement in the therapeutic outcome. CONCLUSIONS: The methodology of RJT in Germany is heterogeneous and still based on the "Marinelli method" in most institutions despite new guidelines and recommendations. A continuous measurement of the iodine kinetics using a wearable probe system could result in further improving the radioiodine test in addition to the newer calculation algorithms.

Population exposure-response model of 131I in patients with benign thyroid disease.

PURPOSE: The study aimed to explore the relationship of different exposure measures with 131I therapy response in patients with benign thyroid disease, estimate the variability in the response, investigate possible covariates, and discuss dosing implications of the results. METHODS: A population exposure-response analysis was performed using nonlinear mixed-effects modelling. Data from 95 adult patients with benign thyroid disease were analysed. Evaluated exposure parameters were: administered radioactivity dose (Aa) [MBq], total absorbed dose (ABD) [Gy], maximum of absorbed dose-rate (MXR) [Gy/h] and biologically effective dose (BED) [Gy]. The response was modelled as ordered categorical data: hyper-, eu- and hypothyroidism. The final model performance was evaluated by a visual predictive check. RESULTS: The probability of the outcome following 131I therapy was best described by a proportional-odds model, including the log-linear model of 131I effect and the exponential model of the response-time relationship. All exposure measures were statistically significant with p<0.001, with BED and ABD being statistically better than the other two. Nevertheless, as BED resulted in the lowest AIC value, it was included in the final model. Accordingly, BED value of 289.7 Gy is associated with 80% probability of successful treatment outcome 12 months after 131I application in patients with median thyroid volume (32.28 mL). The target thyroid volume was a statistically significant covariate. The visual predictive check of the final model showed good model performance. CONCLUSION: Our results imply that BED formalism could aid in therapy individualisation. The larger thyroid volume is associated with a lower probability of a successful outcome.

Improved Patient Dosimetry at Radioiodine Therapy by Combining the ICRP Compartment Model and the EANM Pre-Therapeutic Standard Procedure for Benign Thyroid Diseases.

Radioactive iodine is commonly used for the treatment of different thyroid conditions since the 1940s. The EANM has developed a standard pre-therapeutic procedure to estimate patient specific thyroid uptake at treatment of benign thyroid diseases. The procedure which models the time dependent fractional thyroid uptake is based on a two-compartment fitting system, one representing the thyroid and the other the blood. The absorbed dose is however only estimated for the thyroid and not for any other organ in the body. A more detailed biokinetic model for iodine is given by the ICRP and includes an iodide transport in the whole body. The ICRP model has 30 different compartments and 48 transfer coefficients to model the biokinetics of iodide and to model different transfer for inorganic iodide and organic iodine. The ICRP model is a recirculation iodine model, and the optimization is performed on the whole model and not exclusively on the thyroid as in the EANM procedure. Combining the EANM method and the ICRP model gives both patient specific estimations of thyroid uptake and retention and include most organs in the body. The new software gives both an improved patient specific dosimetry for the thyroid and an estimation of the absorbed dose to non-target organs and tissues like kidneys, urinary bladder, stomach wall, and uterus. Using the method described in this paper, the repercussions on the daily routines will be minimal.

Gender differences in estimating I-131 thyroid uptake from Tc-99m thyroid uptake for benign thyroid disease.

OBJECTIVE: For radioactive Iodine-131 (131I) treatments of thyroid diseases, increased efficacy has been reported for personalized dosimetry treatments. The measurement of Iodine-131 thyroid uptake (131IU) is required in these cases. This study aims to investigate whether 99mTc thyroid uptake (99mTcU) may be used in place of 131IU for implementing personalised treatments. METHODS: A retrospective study of 152 benign thyroid disease 131I treatments was carried out during 2012-2020; 117 treatments were for female patients while 35 were for male patients diagnosed with either Graves' disease, multinodular goitre or toxic nodules. RESULTS: A statistically significant correlation was found between 131IU and 99mTcU data, with the data more correlated for male than female patients (r = 0.71 vs 0.38, p-value < 0.001). Patient age and time difference between the two respective uptake measurements significantly influenced the uptake correlation in females but not for the male cohort, although there was no significant difference between the parameters across gender. Thyroid diagnosis and hormone levels showed a significant correlation with uptakes in both genders. Estimating 131IU based on 99mTcU was shown to be predictive for male but not in female patients (R2 = 91% vs 16%). CONCLUSION: Estimating 131IU based on 99mTcU is not recommended for females at our centre. Males reported good correlation, but a larger sample would be needed for validation. ADVANCES IN KNOWLEDGE: The initial findings showed a significant gender difference in benign thyroid uptake parameters at our centre, highlighting the potential need for gender consideration when planning 131IU patient management and when reporting studies results.

Sialographic Analysis of Radioiodine-Associated Chronic Sialadenitis.

OBJECTIVES/HYPOTHESIS: To apply a novel sialography classification system to identify parotid and submandibular ductal findings following I-131 therapy and to assess correlates to dose and duration of symptoms. STUDY DESIGN: Retrospective single-center case series. METHODS: Patients who underwent sialography between February 2008 and February 2019 after previously receiving I-131 treatment were identified via a retrospective chart review. Their sialograms were systematically evaluated and scored by applying the Iowa parotid sialogram scale to also include submandibular gland analysis. RESULTS: From 337 sialograms, 30 (five submandibular, 25 parotid) underwent analysis. Ductal stenosis was identified in all sialograms and was graded as moderate (>50%-75%) in 7/30 cases and severe (>75%) in 15/30 cases. The distal (main) duct was narrowed in 23/30 cases. No association was identified between degree of ductal stenosis and I-131 dose (P = .39), age (P = .81), or time from I-131 therapy to sialogram (P = .97). CONCLUSIONS: The Iowa parotid sialogram scale was successfully applied to report abnormalities of the parotid and submandibular ductal system. The most common manifestation of I-131-associated sialadenitis was a severe stenosis within the distal salivary duct. No statistically significant association was found between degree of ductal stenosis and dose of I-131, age, or duration of symptoms. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1450-E1456, 2021.

Nuclear thyroidology in pandemic times: The paradigm shift of COVID-19.

Since its outbreak in Wuhan, China the SARS-CoV-2 has become a public health emergency of international concern, impacting all areas of daily life, including medical care. Although not in the front line nuclear medicine practice should adjust their standard operating procedures. The adaptations and the flexibility that nuclear thyroidology, among other fields of nuclear medicine, should show during the pandemic, must focus not only in minimizing the risk of infection to staff, patients, and family members, but also in controlling the transmission of the virus while continuing to provide health care services which do not jeopardize patients' prognosis and quality of life. Favorable prognosis and indolent symptoms of most cases of thyroid diseases, allows postponements and rescheduling as well as alternative procedures, provided that they are cautiously considered for each case individually. The objective of the current paper is to provide guidance on how diagnostic and therapeutic management of patients with thyroid diseases can be safely and effectively adjusted during pandemic, in nuclear medicine settings.

Incidence and risk factors for radioactive iodine-induced sialadenitis.

BACKGROUND: Radioactive iodine (131I) is one of the treatments of hyperthyroidism and differentiated thyroid carcinoma (DTC). Swelling of salivary glands are one of the possible side effects of this treatment, known as radioactive iodine-induced sialadenitis (RAIS). The prevalence of RAIS varies widely and no specific risk ratio has been established. OBJECTIVES: To determine the incidence of RAIS, analysing the epidemiological data and tumour- and treatment-related factors that may influence the development of the disease. MATERIAL AND METHODS: 197 patients who received radioiodine treatment between 2015 and 2017 were studied (76.6% women). The variables studied were age, gender, weight, height, and body mass index; presence of high blood pressure, dyslipidemia, diabetes, and thyroid diseases; cumulative radioiodine dose, presence of sialadenitis, affected salivary gland, and the time of onset. RESULTS: 14 patients developed sialadenitis (78.6% women), all with DTC. The incidence of sialadenitis was 3.4% overall and 6.3% among DTC patients. Furthermore, we found that higher cumulative radioiodine doses confer a greater risk of developing sialadenitis, with a hazard ratio of 1.009 (p = .001). No association was found between the epidemiologic data studied and sialadenitis. CONCLUSIONS: In this series, a dose-dependent relationship was found between radioiodine treatment and sialadenitis.

The effect of radioiodine treatment on the diseased thyroid gland.

Purpose: Radioiodine (I131) therapy is the treatment mainstay for several benign and malignant thyroid disorders, however I131 is known to cause DNA damage and liberation of thyroidal self-antigens inducing secondary immunoreactivity. The exact mechanisms underpinning cellular death and subsequent induction of autoimmune thyroid disease following I131 treatment have not yet been fully elucidated. This manuscript aims to review the literature concerning the effects of I131 on the thyroid gland.Conclusion: The effects of I131 on malignant thyroid cells appears to depend on absorbed dose with the literature demonstrating a clear initial delay in the triggering of apoptosis in response to I131-mediated cellular damage. Some studies also observed necrotic cellular death following high-dose I131 treatment. Liberation of thyroidal self-antigen following I131 treatment helps to explain phenomena such as the subsequent induction of autoimmune thyroid disease. The clinical utility of cytokines and autoantibodies for prognostication of hypothyroidism and treatment failure following I131 remains uncertain and further appropriately-powered studies are required to clarify their role. The potential role of other cell death mechanisms activated after treatment with I131 should also be explored in order to fully delineate the thyroidal response.

Thyroid stunning in radioiodine-131 therapy of benign thyroid diseases.

PURPOSE: Existence and cause of thyroid stunning was controversially discussed for decades but the underlying mechanism remains unclear. Numerous studies describe thyroid stunning in radioiodine-131 therapy (RIT) of differentiated thyroid carcinoma. However, there are no studies evaluating thyroid stunning in benign thyroid diseases caused by the radioiodine uptake test (RIUT). Therefore, the influence of pre-therapeutic tracer radiation dose on therapeutic iodine-131 uptake was evaluated retrospectively. METHODS: A total of 914 RIT patients were included. Exclusion criteria were anti-thyroid drugs, pre- and/or intra-therapeutic effective half-lives (EHL) beyond 8.04 days and externally performed RIUT or 24 h RIUT. All patients received RIUT 1 week before RIT. Thyroid volume was estimated via ultrasound. Tracer radiation dose to the thyroid was calculated retrospectively. The dependence of changes in the pre-therapeutic to the therapeutic extrapolated-maximum-131I-uptake (EMU) from the dose in RIUT was evaluated statistically. RESULTS: EMU in RIUT ranged from 0.10 to 0.82 (median: 0.35) and EMU in RIT ranged from 0.10 to 0.74 (median: 0.33). Averaged over the whole cohort the therapeutic EMU decreased significantly (2.3% per Gray intra-thyroidal tracer radiation dose). A disease-specific evaluation showed dose-dependent thyroid stunning from 1.2% per Gray in solitary toxic nodules (n = 327) to 21% per Gray in goiters (n = 135) which was significant for the subgroups of disseminated autonomies (n = 114), multifocal autonomies (n = 178) and goiters (p < 0.05) but not for Graves' diseases (n = 160) and solitary toxic nodules (p > 0.05). CONCLUSIONS: The presented data indicate for the first time a significant dependence of pre-therapeutic radiation dose on thyroid stunning in goiter and disseminated and multifocal autonomy. To achieve the desired intra-thyroidal radiation dose, RIT activity should be adapted depending on the dose in RIUT.

Radiation Field Strengths Near Cylindrical Volume Sources Via Point-source Correction Factors.

Due to the ease with which the radiation field strength is determined for a point source, the field strength emanating from radiopharmaceutical therapy patients is sometimes estimated by using the point source approximation with a correction factor. It is inevitable that the correction factor will occasionally be used under conditions that do not precisely match those for which the factor was originally derived. The difficulty is that the boundary of the correction factor's domain of acceptability is usually unclear. The purpose of this paper is to address this issue. The patient is modeled as a cylinder containing the radionuclide administered to the patient. From first principles, the expression for converting the radiation field strength of an unshielded point source to that of the extended cylindrical volume source is derived. This expression is analytically separated into the component depicting geometric dispersion of the source material into the volume and the component depicting self-absorption (absorption characteristics of I in water are used). These components, along with their composite, are presented showing their dependence on patient size, distance from the patient, and various dispersion patterns of the source material within the patient. Correlation of theory and measurement is demonstrated, and a conceptual grasp is conveyed regarding field strength variations around volume sources with changes in shape, size, distance, and other parameters. Using data presented, the radiation field strength emanating from a radiopharmaceutical therapy patient can be estimated from the point source approximation and customized for patient size and presumed internal radionuclide distribution.

Investigation of factors influencing radioiodine (131I) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach.

PURPOSE: Radioiodine (131I) therapy is the common treatment option for benign thyroid diseases. The objective of this study was to characterize 131I biokinetics in patients with benign thyroid disease and to investigate and quantify the influence of patients' demographic and clinical characteristics on intra-thyroidal 131I kinetics by developing a population model. METHODS: Population pharmacokinetic analysis was performed using a nonlinear mixed effects approach. Data sets of 345 adult patients with benign thyroid disease, retrospectively collected from patients' medical records, were evaluated in the analysis. The two-compartment model of 131I biokinetics representing the blood compartment and thyroid gland was used as the structural model. RESULTS: Results of the study indicate that the rate constant of the uptake of 131I into the thyroid (ktu) is significantly influenced by clinical diagnosis, age, functional thyroid volume, free thyroxine in plasma (fT4), use of anti-thyroid drugs, and time of discontinuation of therapy before administration of the radioiodine (THDT), while the effective half-life of 131I is affected by the age of the patients. Inclusion of the covariates in the base model resulted in a decrease of the between subject variability for ktu from 91 (3.9) to 53.9 (4.5)%. CONCLUSIONS: This is the first population model that accounts for the influence of fT4 and THDT on radioiodine kinetics. The model could be used for further investigations into the correlation between thyroidal exposure to 131I and the outcome of radioiodine therapy of benign thyroid disease as well as the development of dosing recommendations.

Theranostic radiopharmaceuticals: established agents in current use.

Although use of the term "theranostic" is relatively recent, the concept goes back to the earliest days of nuclear medicine, with the use of radioiodine for diagnosis and therapy of benign and malignant thyroid disease being arguably the most successful molecular radiotherapy in history. A diagnostic scan with 123I-, 124I-, or a low activity of 131I-iodide is followed by therapy with high activity 131I-iodide. Similarly, adrenergic tumours such as phaeochromocytoma and neuroblastoma can be imaged with 123I-metaiodobenzylguanidine and treated with 131I-metaiodobenzylguanidine. Bone scintigraphy can be used to select patients with painful bone metastases from prostate cancer who may benefit from treatment with beta- or alpha-particle emitting bone seeking agents, the most recent and successful of which is 223Ra radium chloride. Anti-CD20 monoclonal antibodies can be used to image and treat non-Hodgkins lymphoma, though this has not been as commercially successful as initially predicted. More recently established theranostics include somatostatin receptor targeting peptides for diagnosis and treatment of neuroendocrine tumours with agents such as 68Ga-DOTATATE and 177Lu-DOTATATE, respectively. Finally, agents which target prostate-specific membrane antigen are becoming increasingly widely available, despite the current lack of a commercial product. With the recent licensing of the somatostatin peptides and the rapid adoption of 68Ga- and 177Lu-labelled prostate-specific membrane antigen targeting agents, we have built upon the experience of radioiodine and are already seeing a great expansion in the availability of widely accepted theranostic radiopharmaceuticals.

Outcome After Radiation Therapy for Langerhans Cell Histiocytosis Is Dependent on Site of Involvement.

PURPOSE: To characterize the efficacy and safety of radiation therapy in a contemporary Langerhans cell histiocytosis (LCH) cohort and to explore whether there are sites at higher risk for local recurrence. PATIENTS AND METHODS: Between 1995 and 2015 we identified 39 consecutive LCH patients who were treated primarily with radiation therapy. Patients were staged by single/multisystem involvement and established risk organ criteria. In 46 irradiated lesions, clinical and radiologic responses were evaluated at multiple time points after radiation therapy. Patient demographics, treatment, and local failure were compared by site of lesion. RESULTS: Median age at radiation therapy was 35 years (range, 1.5-67 years). Twelve patients had multisystem involvement, and of those, 5 patients had disease in organs considered to be high risk. The following sites were irradiated: bone (31), brain (6), skin (3), lymph node (3), thyroid (2), and nasopharynx (1). Median dose was 11.4 Gy (range, 7.5-50.4 Gy). At a median follow-up of 45 months (range, 6-199 months), local recurrence or progression was noted in 5 of 46 lesions (11%). There were no local failures of the 31 bone lesions evaluated, whereas the 3-year freedom from local failure in the 15 non-bone lesions was 63% (95% confidence interval 32-83%; P=.0008). Local failures occurred in 2 of 3 skin lesions, in 2 of 6 brain lesions, and 1 of 3 lymph node lesions. Deaths were recorded in 5 of 39 patients (13%), all of whom were adults with multisystem disease. CONCLUSION: Radiation therapy is a safe and effective measure for providing local control of LCH involving the bone. Whereas bone lesions are well controlled with low doses of radiation, disease in other tissues, such as the skin and brain, may require higher doses of radiation or additional treatment modalities.

Molecular radiotheragnostics in thyroid disease.

Molecular radiotheragnostics directly links nuclear medicine diagnostic imaging to therapy. The imaging study is used to detect a specific molecular target associated with a disease process. A radiotherapeutic molecule with a similar biodistribution to the diagnostic agent can then be used to deliver targeted therapy.Molecular radiotheragnostics have been applied to manage both benign and malignant thyroid disease since the 1940s. The specific molecular pathway targeted is the sodium/iodide symporter (NIS) located on the basolateral membrane of the thyroid follicular cell. Radiolabelling of iodide or a similar ion allows targeting of the NIS system with radiopharmaceuticals for imaging (123I-radioiodine and 99mTc-pertechnetate) and treatment (131I-radioiodine) by virtue of their gamma ray and beta-particle emissions, respectively.Scintigraphic imaging directly guides 131I-radioiodine treatment planning to maximise therapeutic benefit while minimising adverse reactions, in a personalised medicine approach.

Design and implementation of a mobile gamma spectrometry system to in vivo measure the accumulated activity of 131I in patients with thyroid diseases.

The design and implementation of a mobile gamma spectrometry system to in vivo measure the accumulated activity of 131I in whole body and thyroid of patients with thyroid diseases are presented in this work. This system may be used for both pre-therapeutic and post-therapeutic dosimetry calculations. It consists of a detector and a movable support that allows its movement from one place to another.