Radioiodine Therapy For Thyroid Cancer Research Articles

High concordance in intuitive vs standardized assessment of whole-body scintigraphy after radioiodine therapy for thyroid cancer

High concordance in intuitive <i>vs</i> standardized assessment of whole-body scintigraphy after radioiodine therapy for thyroid cancer

Lacrimal and Salivary Gland Dysfunction Following Radioiodine Therapy for Thyroid Cancer

Lacrimal and Salivary Gland Dysfunction Following Radioiodine Therapy for Thyroid Cancer

Radioiodine therapy for thyroid cancer and dyfunction of the salivary and lachrymal glands in the start study: results at 6 months follow-up

Radioiodine therapy for thyroid cancer and dyfunction of the salivary and lachrymal glands in the start study: results at 6 months follow-up

Анализ результатов хирургического лечения пациентов с облитерацией слезоотводящих путей вследствие терапии радиоактивным йодом

Relevance. Nasolacrimal duct obstruction occurs in 9% of patients after radioiodine therapy for thyroid cancer. The surgical interventions used in this case have not been studied enough; indications for certain operations have not been developed. Purpose. To evaluate clinical efficacy of surgical treatment in patients with nasolacrimal duct obstruction due to radioactive iodine therapy. Material and methods. The outcomes of 47 surgeries in patients with secondary acquired nasolacrimal duct obstruction due to radioiodine therapy were analyzed, among them 30 cases of dacryocystorinostomy and 17 cases of recanalization of the tear ducts. In 15 cases, dacryocystorinostomy was supplemented by the formation of an anastomosis in the area of the Hasner's valve. A comparative analysis of the effectiveness of surgical intervention depending on the localization of obstruction was carried out. Results. Dacryocystorinostomy was effective in 90% of cases, recanalization of the tear ducts – in 13% of cases. The analysis revealed that in cases of obstruction at the level of the lacrimal sac, the success of dacryocystorinostomy was 100% (5 observations), with obstruction at the level of the middle part of the nasolacrimal duct – 85.7% (12 observations), with obstruction at the level of the Hasner's valve – 100% (6 observations). Recanalization of the tear ducts was characterized by success in 100% of cases (1 observation) with obstruction of the middle part of the nasolacrimal duct and in 6.3% of cases (1 observation) with obstruction at the level of Hasner's valve. Conclusion. Dacryocystorinostomy is an effective intervention in patients with secondary acquired nasolacrimal duct obstruction due to radioiodine therapy. Recanalization of the tear ducts is characterized by low efficiency. The analysis of the effectiveness of these interventions, considering the localization of obstruction of the tear ducts, showed that the effectiveness of surgical treatment may vary depending on the level of obstruction. In cases of anatomically low obstruction of the tear ducts, dacryocystorinostomy was supplemented by the formation of an anastomosis in the area of the Hasner's valve. Recanalization of the tear ducts was characterized by greater efficiency in cases where the level of obstruction of the tear ducts was higher than the Hasner's valve than directly at Hasner's valve. The choice of treatment tactics for patients with secondary acquired nasolacrimal duct obstruction due to radioiodine therapy should be differentiated depending on the localization of the tear duct obstruction. Key words: tear ducts, radioiodine, dacryocystorhinostomy, nasolacrimal duct intubation

Redifferentiation-facilitated radioiodine therapy in thyroid cancer.

Based on experimental data, the inhibition of the MAPkinase pathway in patients with radioiodine-refractory thyroid cancer was capable of inducing a redifferentiation. Preliminary data obtained in a small series of patients were encouraging and this strategy might become an alternative treatment in those patients with a druggable mutation that induces a stimulation of the MAP kinase pathway. This is an active field of research to answer many still unresolved questions.

Parathyroid Hormone Level Changes Following Radioiodine Therapy for Thyroid Cancer: A Prospective Observational Study

ObjectiveOur objective was to analyze the effect of radioiodine (RAI) therapy on parathyroid hormone (PTH) secretion. MethodsA total of 137 patients were included and divided into 2 groups based on pretherapy PTH levels. The residual thyroid tissue volume was classified into 4 grades (0-3), and a value of 0 indicated that there was no apparent residual tissue. We analyzed the PTH level changes among different time points in each group and the factors that could predict the PTH level changes. ResultsIn 113 patients with normal parathyroid gland function, the PTH level at baseline, 1 day, 7 days, 1 month, 3 months, and 6 months after RAI therapy did not show any significant difference; in 24 patients with decreased parathyroid gland function, the level of PTH immediately decreased after the implementation of RAI therapy but gradually returned to a pre-RAI therapy level within 6 months. On the seventh day after therapy, the mean value of PTH in patients with a residual thyroid tissue volume of extent of 0/1 was 8.0 ± 2.3 pg/mL, which was significantly higher than that in patients with a residual thyroid tissue volume of extent of 2/3 (P = .011). Similar phenomena were observed 1 month, 3 months, and 6 months after therapy. ConclusionRAI therapy had a significant transient adverse effect on parathyroid gland function in patients with decreased PTH secretion pretherapy, and the extent was associated with the amount of residual thyroid tissue.

Radioiodine therapy for thyroid cancer

Radioiodine therapy for thyroid cancer

HMGB1-mediated autophagy regulates sodium/iodide symporter protein degradation in thyroid cancer cells

BackgroundSodium/iodide symporter (NIS)-mediated iodide uptake plays an important physiological role in regulating thyroid gland function, as well as in diagnosing and treating Graves’ disease and thyroid cancer. High-mobility group box 1 (HMGB1), a highly conserved nuclear protein, is a positive regulator of autophagy conferring resistance to chemotherapy, radiotherapy and immunotherapy in cancer cells. Here the authors intended to identify the role of HMGB1 in Hank’s balanced salt solution (HBSS)-induced autophagy, explore NIS protein degradation through a autophagy-lysosome pathway in thyroid cancer cells and elucidate the possible molecular mechanisms.MethodsImmunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) were performed for detecting the expression of HMGB1 in different tissues. HMGB1 was knocked down by lentiviral transfection in FTC-133/TPC-1 cells. Autophagic markers LC3-II, p62, Beclin1 and autophagosomal formation were employed for evaluating HMGB1-mediated autophagy in HBSS-treated cells by Western blot, immunofluorescence and electron microscopy. Western blot, quantitative RT-PCR and gamma counter analysis were performed for detecting NIS expression and iodide uptake in HMGB1-knockdown cells after different treatments. The reactive oxygen species (ROS) level, ROS-mediated LC3-II expression and HMGB1 cytosolic translocation were detected by fluorospectrophotometer, flow cytometry, Western blot and immunofluorescence. HMGB1-mediated AMPK, mTOR and p70S6K phosphorylation (p-AMPK, p-mTOR & p-p70S6K) were detected by Western blot. Furthermore, a nude murine model with transplanted tumor was employed for examining the effect of HMGB1-mediated autophagy on imaging and biodistribution of 99mTcO4−. NIS, Beclin1, p-AMPK and p-mTOR were detected by immunohistochemical staining and Western blot in transplanted tumor samples.ResultsHMGB1 was a critical regulator of autophagy-mediated NIS degradation in HBSS-treated FTC-133/TPC-1 cells. And HMGB1 up-regulation was rather prevalent in thyroid cancer tissues and closely correlated with worse overall lymph node metastasis and clinical stage. HMGB1-knockdown dramatically suppressed autophagy, NIS degradation and boosted iodide uptake in HBSS-treated cells. Moreover, HBSS enhanced ROS-sustained autophagy and promoted the cytosolic translocation of HMGB1. A knockdown of HMGB1 suppressed LC3-II conversion and NIS degradation via an AMPK/mTOR-dependent signal pathway through a regulation of ROS generation, rather than ATP. Furthermore, these data were further supported by our in vivo experiment of xenografts formed by HMGB1 knockdown cells reverting the uptake of 99mTcO4− as compared with control shRNA-transfected cells in hunger group.ConclusionsActing as a critical regulator of autophagy-mediated NIS degradation via ROS/AMPK/mTOR pathway, HMGB1is a potential intervention target of radioiodine therapy in thyroid cancer.

The role of 124I PET/CT lesion dosimetry in differentiated thyroid cancer.

Radioiodine therapy of thyroid cancer was the first successful radionuclide therapy in the treatments of cancer, although its clinical use is empirical and not based on precise dosimetry. 124I is a positron-emitting radionuclide and positron emission tomography/computed tomography (PET/CT) with 124I currently provides the most accurate estimation of the absorbed (radiation) dose to thyroid cancer lesions. In the application, serial 124I PET/CT scans are performed to determine the time uptake curves and to delineate the volumes of the lesions. The 124I data are then used to project the absorbed dose per unit administered 131I activity. The results are part of the decision-making process to individually guide treatment plans, in particular by tailoring the therapeutic 131I activity in radioiodine therapy. The aim of this review is to provide an overview of 124I PET/CT lesion dosimetry of differentiated thyroid cancer including: 1) an historical overview; 2) the general properties of 124I and its activity measurement; 3) the main factors impairing PET image quantification; 4) an optimized lesion dosimetry protocol used in our group to make this manuscript self-contained; as well as 5) a summary of important clinical studies.

Radiopharmaceutical Therapy.

Radiopharmaceutical therapy involves the use of radionuclides that are either conjugated to tumor-targeting agents (e.g., nanoscale constructs, antibodies, peptides, and small molecules) or that concentrate in tumors through natural physiological mechanisms that occur predominantly in neoplastic cells. In the latter category, radioiodine therapy of thyroid cancer is the prototypical and most widely implemented radiopharmaceutical therapy. In the category of radionuclide-ligand conjugates, antibody and peptide conjugates have been studied extensively. The efficacy of radiopharmaceutical therapy relies on the ability to deliver cytotoxic radiation to tumor cells without causing prohibitive normal tissue toxicity. After some 30 y of preclinical and clinical research, a number of recent developments suggest that radiopharmaceutical therapy is poised to emerge as an important and widely recognized therapeutic modality. These developments include the substantial investment in antibodies by the pharmaceutical industry and the compelling rationale to build upon this already existing and widely tested platform. In addition, the growing recognition that the signaling pathways responsible for tumor cell survival and proliferation are less easily and durably inhibited than originally envisioned has also provided a rationale for identifying agents that are cytotoxic rather than inhibitory. A number of radiopharmaceutical agents are currently undergoing clinical trial investigation; these include beta-particle emitters, such as Lu, that are being used to label antisomatostatin receptor peptides for neuroendocrine cancers and also prostate-specific membrane antigen targeting small molecules for prostate cancer. Alpha-particle-emitting radionuclides have also been studied for radiopharmaceutical therapy; these include At for glioblastoma, Ac for leukemias and prostate cancer, Pb for breast cancer, and Ra for prostate cancer. The alpha emitters have tended to show particular promise, and there is substantial interest in further developing these agents for therapy of cancers that are particularly difficult to treat.

我が国のRAI治療の現状―海外の現状との比較，RAI不応性の判定について

我が国のRAI治療の現状―海外の現状との比較，RAI不応性の判定について

Analysis of Iodine Content in Salts and Korean Sauces for Low-Iodine Diet Education in Korean Patients with Thyroid Cancer Preparing for Radioiodine Therapy.

A low-iodine diet is necessary in patients about to undergo radioiodine therapy for thyroid cancer to decrease the competitive absorption of ingested nonradioactive iodine. This study aimed to assess the iodine concentrations in salts and basic Korean sauces, and to provide fundamental data for guidelines on a low-iodine diet before radioiodine therapy. The iodine contents of refined salts, solar sea salts, fish sauces, and commonly used Korean sauces with added refined salt were determined by ICP-MS. The iodine content of refined salts was found to be very low (0.033±0.05μg/100g) compared with that of solar sea salts (434±73.6μg/100g). The iodine contents of Korean soy sauce, Korean soybean paste, Gochujang seasoned with refined salt were also very low (0.010, 0.044, 0.002μg/100g, respectively). However, the mean iodine contents of the shrimp and fish Jeots analyzed in this study were found to be 41.3 ± 4.2 and 24.8 ± 4.5μg/100g, respectively. This study is the first to investigate the iodine contents of the salts and basic sauces used in Korea. The results show that refined salts and Korean traditional sauces seasoned with them can be safely used in low-iodine diets before radioiodine therapy.

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

This study set out to investigate chromosomal damage in peripheral blood lymphocytes of thyroid cancer patients receiving 131I 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 4days after administration of 2-4GBq of 131I. 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 0.62Gy (95% CI: 0.44-0.77Gy) in the subgroup of patients treated one time and 0.67Gy (95% CI: 0.03-1.00Gy) 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.

Time course of Graves' orbitopathy after total thyroidectomy and radioiodine therapy for thyroid cancer.

The risk of cancer is relatively higher in Graves’ patients presenting simultaneously with thyroid nodules. Radioiodine (RAI) therapy recommended in high-risk differentiated thyroid carcinoma may be associated with worsening of a pre-existing Graves’ orbitopathy (GO) or developing a new onset. The impact of RAI therapy in patients with differentiated thyroid cancer on the course of a pre-exisiting GO has not been specifically investigated.The aim of this study is to assess the influence of RAI treatment administered for differentiated thyroid cancer on the course of a pre-existing GO.This is a retrospective multicenter study including 35 patients from the University Hospital of Clermont-Ferrand (7 patients) and Lyon-Est (6 patients) in France and from a literature review published as case reports or studies (22 patients).Seven patients exhibited a worsened pre-existing GO after total thyroidectomy followed by RAI treatment for thyroid cancer. Older men, those who initially presented with a lower clinical score of GO before RAI therapy, received higher doses of 131I especially when prepared with recombinant thyroid-stimulating hormone, and/or not prepared with glucocorticoids during RAI are at a higher risk to worsen their GO.This study is the first and complete study collection. We describe worsening of GO in 20% of patients after RAI treatment for thyroid cancer and determine a pool of predictive factors.

Therapy-related acute myeloid leukemia following radioactive iodine treatment for thyroid cancer.

Therapy-related acute myeloid leukemia (t-AML) associated with radioiodine treatment (RAI) is emerging as an important clinical entity with the rise in incidence of thyroid cancer. We conducted an electronic search of MEDLINE and EMBASE, and also searched reference lists of articles and abstracts from conference proceedings for case reports and review articles on t-AML following radioiodine therapy. A total of 37 patients with acute myeloid neoplasms following radioiodine treatment were analyzed. The median RAI dose was 324 mCi, and median age was 47.5 years with M/F ratio of 1:3. Latency period was 1-4 years, and the median time from RAI exposure to diagnosis of t-AML was 2.9 years. FAB M2 and M3 were the two most common t-AML subtypes reported. Seventy-one percent of the cases that reported cytogenetic abnormalities were classified as unfavorable. The most commonly reported abnormalities were del 5q and t(15:17). Survival outcomes were not reported due to lack of patient-level data. T-AML following radioiodine therapy for thyroid cancer appears to have a shorter latency period than other types of t-AML, which is an important consideration for post-therapy surveillance. Reporting of cases and outcomes will help provide data for further research. Identifying biomarkers that help risk-stratify patients prior to therapy and specific genetic-guided therapies may help improve outcomes.

Modulation of thyroidal radioiodide uptake by oncological pipeline inhibitors and Apigenin.

Targeted radioiodine therapy for thyroid cancer is based on selective stimulation of Na+/I- Symporter (NIS)-mediated radioactive iodide uptake (RAIU) in thyroid cells by thyrotropin. Patients with advanced thyroid cancer do not benefit from radioiodine therapy due to reduced or absent NIS expression. To identify inhibitors that can be readily translated into clinical care, we examined oncological pipeline inhibitors targeting Akt, MEK, PI3K, Hsp90 or BRAF in their ability to increase RAIU in thyroid cells expressing BRAFV600E or RET/PTC3 oncogene. Our data showed that (1) PI3K inhibitor GDC-0941 outperformed other inhibitors in RAIU increase mainly by decreasing iodide efflux rate to a great extent; (2) RAIU increase by all inhibitors was extensively reduced by TGF-β, a cytokine secreted in the invasive fronts of thyroid cancers; (3) RAIU reduction by TGF-β was mainly mediated by NIS reduction and could be reversed by Apigenin, a plant-derived flavonoid; and (4) In the presence of TGF-β, GDC-0941 with Apigenin co-treatment had the highest RAIU level in both BRAFV600E expressing cells and RET/PTC3 expressing cells. Taken together, Apigenin may serve as a dietary supplement along with small molecule inhibitors to improve radioiodine therapeutic efficacy on invasive tumor margins thereby minimizing future metastatic events.

The Nuclear Medicine Therapy Care Coordination Service: A Model for Radiologist-Driven Patient-Centered Care

We developed a longitudinal care coordination service to proactively deliver high-quality and family-centered care in patients receiving radioiodine therapy for thyroid cancer. In an iterative, multidisciplinary team manner, a pretherapy consultation service, which included scripted interactions, documentation, and checklists for quality control, evolved over time into a robust patient-centered longitudinal care coordination nuclear medicine service. Radiation safety precautions, the rationale for therapy, and management of patient expectations were addressed through the initial consultation, and discharge and posttreatment care were managed during subsequent follow-up. The patient-physician relationship created during longitudinal nuclear medicine therapy care is one tool to help counteract the growing commoditization of radiology. This article describes the process that the nuclear medicine specialists in our department established to enhance radiologist value by providing both exceptional thyroid cancer treatment and continuity of care.

Radiation safety in the management of patients undergoing radioactive iodine ablation therapy.

High-dose radioiodine therapy for thyroid cancer poses risks to healthcare workers, family members, and the public. Oncology nurses can effectively manage these risks by employing the three key principles of time, distance, and shielding.

A novel hNIS/tdTomato fusion reporter for visualizing the relationship between the cellular localization of sodium iodide symporter and its iodine uptake function under heat shock treatment.

The function of membrane-localized sodium iodide symporter (NIS) determines the efficacy of radioiodine therapy in thyroid cancer. Here, we describe a dual mode reporter fused with human NIS (hNIS) and a red fluorescent protein named tandem dimeric Tomato (tdTomato) for the in vitro and in vivo imaging of hNIS protein expression, localization, and iodide uptake function. Human cervical epithelial adenocarcinoma cell line (HeLa)-hNIS/tdTomato cells were established by transducing a fusion gene expressing hNIS/tdTomato under the control of a cytomegalovirus promoter. Fluorescence imaging, confocal microscopy, and an 125I uptake assay were performed to validate the integrity of the fusion protein. Actinomycin D and cycloheximide were used to block newly synthesized hNIS proteins. In vivo images were acquired using a gamma camera and a Maestro fluorescence imaging device. The fluorescence intensity of membrane-localized hNIS and 125I uptake both were increased after heat shock. Scintigraphy and fluorescence imaging indicated specific accumulation of the hNIS/tdTomato fusion protein in xenografted tumors, supporting the utility of this system for in vivo monitoring of hNIS expression and activity. We developed a novel hNIS/tdTomato dual mode reporter that enables visualization of the expression, localization, and iodine uptake function of hNIS in vitro and in vivo.

Chewing-gum stimulation did not reduce the absorbed dose to salivary glands during radioiodine treatment of thyroid cancer as inferred from pre-therapy (124)I PET/CT imaging.

BackgroundThe goal of this prospective study was to estimate the absorbed (radiation) doses to salivary glands in radioiodine therapy of thyroid cancer under chewing-gum stimulation using 124I positron emission tomography (PET)/computed tomography (CT) imaging.MethodsDuplex ultrasonography was conducted in three test persons for visual comparison of the glandular blood flow with three different stimulation types (no stimulation, chewing tasteless gum base, sucking on lemon slices). Ten patients with newly diagnosed differentiated thyroid cancer received 124I PET/CT dosimetry after thyroidectomy and prior to radioiodine therapy. Patients underwent a series of three 124I PET/CT scans (4, 24, and ≥96 h after administration of 23 MBq 124I). They were instructed to chew gum base (tasteless) approximately 20 min after ingesting the 124I-containing capsule in the course of the first day. Absorbed doses per administered 131I activity to the salivary glands were calculated and compared with the previously published results of the lemon-juice stimulation and non-stimulation groups.ResultsThe sonograms in the three test persons showed that glandular blood perfusion by lemon-juice stimulation was clearly increased compared with non-stimulation or chewing of gum base. The sonogram comparison between the chewing-gum stimulation and non-stimulation demonstrated a minor increase of blood flow for the gum base-stimulated salivary glands. The mean ± standard deviation of the absorbed dose per activity under chewing-gum stimulation for the submandibular and parotid glands (within parentheses) was 0.22 ± 0.09 Gy/GBq (0.22 ± 0.08 Gy/GBq). Compared with the absorbed doses of the non-stimulation group, 0.24 ± 0.08 Gy/GBq (0.21 ± 0.05 Gy/GBq), those of the chewing-gum stimulation group showed no significant change (P > 0.60), but the absorbed doses of the lemon-juice stimulation group, 0.35 ± 0.14 Gy/GBq (0.33 ± 0.09 Gy/GBq), were significantly higher (P < 0.04) than those of the chewing-gum stimulation group.ConclusionsThe results suggest that salivary flow induced by chewing gum base does not cause a significant reduction of the salivary gland absorbed dose compared with that in the non-stimulation group. The increased blood flow appears to be a decisive factor causing the increased 131I absorbed doses in the lemon-juice stimulation group.