131I Therapy Research Articles

Downregulation of miR-146b-3p Inhibits Proliferation and Migration and Modulates the Expression and Location of Sodium/Iodide Symporter in Dedifferentiated Thyroid Cancer by Potentially Targeting MUC20.

The dedifferentiation of differentiated thyroid cancer (DTC) is a challenging problem for radioactive iodine (131I) treatment, also known as radioiodine refractory differentiated thyroid cancer (RAIR-DTC). The purpose of this study was to further explore the mechanism of the redifferentiation of dedifferentiated thyroid cancer. Ineffective and effective groups of 131I therapy were analyzed and compared in both our clinical and TCGA samples. Whole-exome sequencing, mutation analysis, transcriptome analysis, and in vitro functional experiments were conducted. FLG, FRG1, MUC6, MUC20, and PRUNE2 were overlapping mutation genes between our clinical cases, and the TCGA cases only appeared in the ineffective group. The expression of miR-146b-3p target MUC20 was explored. The expression levels of miR-146b-3p and MUC20 were significantly increased, and the inhibition of miR-146b-3p expression significantly inhibited proliferation and migration, promoted apoptosis, regulated the expression and location of thyroid differentiation-related genes, and sodium/iodide symporter (NIS) in dedifferentiated thyroid cancer cells (WRO). Thus, miR-146b-3p potentially targets MUC20 participation in the formation of DTC dedifferentiation, resulting in resistance to 131I and the loss of the iodine uptake ability of DTC cancer foci, promoting refractory differentiated thyroid cancer. miR-146b-3p may be a potentially therapeutic target for the reapplication of 131I therapy in dedifferentiated thyroid cancer patients.

Is There Any Need for Adjusting 131I Activity for the Treatment of High Turnover Graves' Disease Compared to Normal Turnover Patients? Results from a Retrospective Cohort Study Validated by Propensity Score Analysis.

To compare 131I-therapy outcomes in high turnover and normal turnover Graves' disease patients and predict optimal first 131I activity for high turnover patients. Retrospective cohort design (1:2) validated by propensity score analysis. Cohort 1, high turnover (2-h RAIU/24-h RAIU ≥ 1), n = 104, and cohort 2, normal turnover (ratio < 1), n = 208, patients were compared for post 131I outcome. The cure was defined as a combined euthyroid and stable hypothyroid state following 131I treatment. Logistic regression analysis was used for identifying prognostic factors. The propensity score was applied; 77 matched pairs (1:1 ratio) of high and normal turnover patients were selected as a validation set. First 131I cure rates of 28% in high turnover and 66% in normal turnover groups (p = 0.001) were noted. The therapy cycles (median, 2 vs. 1) and cumulative 131I activity (median, 15 vs. 7mCi) were required to cure hyperthyroidism in cohort 1 and cohort 2, respectively. Age (> 44years), higher grade of goitre, and 2-h RAIU (> 37%) were associated with 131I therapy failure. The high turnover patients needed a factor of 1.5-2 times more 131I activity to achieve a similar cure rate compared to the normal turnover patients. The first-dose cure rate was 31% vs. 60% by propensity score analysis (n = 154), no way different (28% vs.66%) from the whole group of 312 patients. High turnover Graves' disease patients, if administered standard 131I activity, the outcomes shall be poor. To improve the success rate, 131I activity should be increased by 1.5 to 2 times in the high turnover patients. The online version contains supplementary material available at 10.1007/s13139-020-00674-3.

Salivary flow rate and radioactivity in saliva, blood and serum of benign and malignant thyroid patients after 131I therapy

Salivary flow rate and radioactivity in saliva, blood and serum of benign and malignant thyroid patients after 131I therapy

Early Quantification of Salivary Gland Function after Radioiodine Therapy.

Purpose of the Study:Radioiodine (I-131) is used as an effective noninvasive treatment for thyroid malignancies. Salivary gland is one of the most affected nontarget organs. The present study aims to perform early quantification of salivary gland function after I-131 therapy (RIT) for thyroid cancer considering I-131 down-scatter in the Tc-99m window.Materials and Methods:A total of 20 patients (6 males and 14 females) with differentiated thyroid carcinoma were enrolled in the study. Baseline dynamic salivary scintigraphy was performed in all patients using 185–370 MBq (5–10 mCi) Tc-99m pertechnetate. Posttherapy, salivary scintigraphy was performed 10–25 days after RIT in the range of 1.85–7.4 GBq (50–200 mCi). Time–activity curves obtained from the pre- and posttherapy dynamic salivary scintigraphy were used for semi-quantitative analysis. Uptake ratio (UR), ejection fraction (EF%), and maximum accumulation (MA%) were calculated by drawing regions of interest of individual parotid and submandibular glands over a composite image, after correcting for down-scatter from I-131 in the Tc-99m window. A paired t-test was used for comparison of the parameters obtained.Results:Significant changes were observed in UR and EF% of both parotid and submandibular glands (P < 0.05). No significant changes were found in the value of MA% of left parotid gland and both submandibular glands in the posttherapy scans in comparison to pretherapy scans (P > 0.05). However, significant difference was observed in the MA% of the right parotid gland (P = 0.025).Conclusion:Salivary gland function was found to deteriorate after RIT, with the parotid glands affected more than the submandibular glands.

123I Scan With Whole-Body Retention Measurement at 48 Hours for Simplified Dosimetry Before 131I Treatment of Metastatic Thyroid Cancer.

A previously published model (Atkins) allows for calculation of 131I maximum tolerated activity on the basis of 48-hour whole-body retention of 131I on a pretherapy diagnostic scan. Our practice uses iodine 123I for diagnostic imaging of metastatic thyroid cancer for staging before 131I therapy, with images typically acquired 24 hours after administration of the radiopharmaceutical. We explored the feasibility of an additional 123I whole-body scan and retention measurement at 48 hours, with application of the model to estimate maximum tolerated activity of radioiodine before 131I treatment of metastatic thyroid cancer.

The spectrum of 124I uptake in the lacrimal gland and nasolacrimal sac/duct on PET/CT imaging.

124I PET/CT in 31 DTC patients was performed at 2, 24, 48, 72, and 96 h after oral administration of 31.5 or 62.9 MBq (0.85 or 1.7 mCi) of 124I after either recombinant human thyroid-stimulating hormone injections or thyroid hormone withdrawal. All but two patients had a history of prior 131I therapy. Patterns of 124I uptake in the lacrimal glands and nasolacrimal sac/ducts (NLD) were assessed. A total of 173 individual 124I PET/CT scans (forming 35 sets of scans) were reviewed for 31 patients. Lacrimal glands were visualized bilaterally in only 4 patients. The focal mild uptake (grade 2), best seen on the 2-h images, was crescent-shaped and located in the lateral upper quadrant of the orbit. In contrast, the NLDs were identified in all patients (bilateral in 29 of 31 patients) with high focal uptake (grade 4) peaking on the 2- and 24-h timepoints; however, the overall pattern of uptake was variable. Of the 29 patients with prior 131I therapy, three patients had a relatively fixed and unchanging pattern of uptake on at least one side of the NLDs. In patients with DTC, 124I activity in the NLDs is more frequently visualized, more intense, more prolonged, and more variable than in the lacrimal glands. The lack of clearance may suggest possible obstruction or stasis of an NLD.

Prognostic value and dynamics of antithyroglobulin antibodies for differentiated thyroid carcinoma.

Background: The clinical value of antithyroglobulin antibodies (TgAb) as a tumor marker for differentiated thyroid cancer (DTC) is still controversial. Materials & methods: We studied 110 TgAb positive DTC patients who underwent total thyroidectomy and 131I therapies. Multivariate logistic regression was conducted to analyze the association between prognostic factors and disease outcomes. Results & conclusion: Pre-ablation TgAb levels and the changes of TgAb in 6-12 months after the first 131I therapy were risk factors for disease outcome in patients younger than 55, while extrathyroid extensionwas a risk factor in patients older than 55. The median TgAb half-life was 7.7monthsand the median time for TgAb positivity to become negative was 15.8months. The dynamics of TgAb within the first year after remnant ablation could predict disease outcome for DTC patients.

Sialographic Analysis of Radioiodine-Associated Chronic Sialadenitis.

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. Retrospective single-center case series. 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. 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). 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. 4 Laryngoscope, 131:E1450-E1456, 2021.

Measurement of Radiation Exposure to Caregivers of Patients with Thyroid Diseases Treated with Iodine-131: A Review

This review paper aimed to examine radiation safety issues related to relatives as well as caregivers of patients with thyroid diseases treated with radioiodine (I-131). During I-131 therapy for thyroid disorders such as hyperthyroidism, patients receiving I-131 doses (200-800 MBq) emit radioactive radiations which pose a prospective risk to other people. Critical groups are patients’ visitors and families, especially children. Following the updated international guidelines, the doses received by members of the public as a proportion of the therapy of a patient have been decreased. The public annual dose limits are 1 mSv, although higher doses are permitted for adults in the patient’s family, provided that the maximum 5 mSv is not surpassed for 5 years. Without compliance with the current recommendations, extended hospitalizations for patients are essential. Family members should therefore limit close interactions with an individual for some duration following thyroid therapy with I-131.

Perioperative diagnostics of patients referred for radioiodine therapy of differentiated thyroid carcinoma: referral center experience in an iodine-insufficient country

PurposeThe interdisciplinary “Martinique-Principles” of four international professional societies concerned with the patient management of differentiated thyroid cancer (DTC) patients were agreed upon. Differences in perioperative diagnostics can lead to differences in clinical decision founding regarding the treatment of thyroid carcinoma. Our aim was to analyze the perioperative diagnostics of patients referred for postoperative I-131 therapy of DTC.MethodsWe retrospectively examined the data of 142 patients who were referred to our center for the first course of postsurgical I-131 therapy. We extracted data on perioperative diagnostics.ResultsFine-needle biopsy (FNB) was performed in 27/142 patients. In 17 patients, FNB yielded findings suspicious of malignancy, in 3 patients a follicular lesion was reported. An intraoperative frozen section analysis was performed in 79/142 patients. 5/63 patients showed already a cytologically proven malignancy. In 10/79 patients, the frozen section had a nonmalignant result, although DTC was found on final assessment. In 2/79 patients, frozen section analysis was indecisive, although the final report confirmed DTC. In the remaining 67 patients, frozen section yielded DTC.ConclusionsThere is room for improvement in perioperative diagnostics surrounding thyroid surgery, currently many procedures are performed without adequate information on potential presence of thyroid cancer. More frequent use of FNB might be able to decrease the number of unnecessary thyroid surgeries, increased use of frozen section might decrease the number of second operations and might contribute to less discordance between experts in the field of DTC treatment.

Ablation therapy using a low dose of radioiodine may be sufficient in low- to intermediate-risk patients with follicular variant papillary thyroid carcinoma.

ObjectivesFollicular variant papillary thyroid carcinoma (FVPTC) is treated similarly to classical variant papillary thyroid carcinoma (cPTC). However, FVPTC has unique tumour features and behaviours. We investigated whether a low dose of radioiodine was as effective as a high dose for remnant ablation in patients with FVPTC and evaluated the recurrence of low-intermediate risk FVPTC.MethodsData from cPTC and FVPTC patients treated with I-131 from 2004 to 2014 were reviewed. Demographics, tumour behaviour, lymph node metastasis, and local recurrence data were compared between FVPTC and cPTC patients. Then, low-intermediate risk FVPTC patients were divided into low, intermediate, and high I-131 dose groups, and postoperative I-131 activities were analysed to evaluate the effectiveness of I-131 therapy for thyroid remnant ablation.ResultsIn total, 799 cases of FVPTC (n = 168) and cPTC (n = 631) treated with I-131 were identified. Patients with FVPTC had a larger primary nodule size than cPTC, but lymph node metastases and local recurrence were more prevalent in cPTC than in FVPTC. For the low-, intermediate-, and high-dose groups, success rates of ablation did not differ (82.0%, 80%, and 81.3%, respectively).ConclusionFVPTC differs from cPTC in behaviour. Low-dose ablation may be sufficient in FVPTC patients with low-intermediate disease risk.

Papillary Thyroid Carcinoma in Children: Clinicopathological Profile and Outcomes of Management.

We aim to analyze the clinicopathological profile and outcomes of management for children with papillary thyroid carcinoma (PTC). Relevant clinical data of children ≤ 18years of age managed for PTC between January 2006 and July 2018 as well as details of their follow-up till December 2019 were retrospectively collected and analyzed. There were 82 children with PTC that were managed during the study period. At presentation, 39 (47.6%) had cervical lymphadenopathy, while 9 (11%) had systemic metastasis. Majority of patients 39 (47.6%) underwent total thyroidectomy with a selective neck dissection, while total thyroidectomy alone was performed in 26 (31.7%). Following surgery, hypocalcemia was seen in 39 (47.6%): 28 (34.1%) were temporary, while 11 (13.4%) were permanent. Twenty-eight (34%) developed persistent disease after surgery and 131I therapy. Significant risk factors for persistence and metastatic disease were metastatic cervical lymph node at presentation (p = 0.002) and tumor size (p = 0.014), respectively. The mean duration of follow-up was 60.3 (range 12-150) months with a mean overall disease-free survival of 60months (95% CI 57.11, 77.95). Children with papillary thyroid cancers present with aggressive disease, 47.6% with cervical nodal metastasis and 11% with distant metastasis in this cohort. The rate of post-thyroidectomy hypocalcemia in this study is substantial, and efforts to reduce it are actively being pursued. The presence of metastatic cervical lymph node at presentation (p = 0.002) and tumor size (p = 0.014) were the only significant risk factors for persistent and metastatic disease, respectively, in this study.

Regional Hyperthermia Enhances Mesenchymal Stem Cell Recruitment to Tumor Stroma: Implications for Mesenchymal Stem Cell-Based Tumor Therapy

The tropism of mesenchymal stem cells (MSCs) for tumors forms the basis for their use as delivery vehicles for the tumor-specific transport of therapeutic genes, such as the theranostic sodium iodide symporter (NIS). Hyperthermia is used as an adjuvant for various tumor therapies and has been proposed to enhance leukocyte recruitment. Here, we describe the enhanced recruitment of adoptively applied NIS-expressing MSCs to tumors in response to regional hyperthermia. Hyperthermia (41°C, 1 h) of human hepatocellular carcinoma cells (HuH7) led to transiently increased production of immunomodulatory factors. MSCs showed enhanced chemotaxis to supernatants derived from heat-treated cells in a 3D live-cell tracking assay and was validated invivo in subcutaneous HuH7 mousexenografts. Cytomegalovirus (CMV)-NIS-MSCs were applied 6-48h after or 24-48h before hyperthermia treatment. Using 123I-scintigraphy, thermo-stimulation (41°C, 1 h) 24h after CMV-NIS-MSC injection resulted in a significantly increased uptake of 123I in heat-treated tumors compared with controls. Immunohistochemical staining and real-time PCR confirmed tumor-selective, temperature-dependent MSC migration. Therapeutic efficacy was significantly enhanced bycombining CMV-NIS-MSC-mediated 131I therapy with regional hyperthermia. We demonstrate here for the first time that hyperthermia can significantly boost tumoral MSC recruitment, thereby significantly enhancing therapeutic efficacy of MSC-mediated NIS gene therapy.

No difference in the outcome of metastatic thyroid cancer patients when using recombinant or endogenous TSH.

At present, recombinant TSH cannot be used for the treatment of metastatic differentiated thyroid cancer patients. The aim of this study was to evaluate if the type of TSH stimulation, recombinant or endogenous, had an impact on the outcome of these patients. We compared the outcome of two propensity score-matched groups of metastatic patients, stimulated by either only recombinant TSH (n = 43) or only endogenous TSH (n = 34). As expected from the matching procedure, the clinical-pathological features and the cumulative 131-I activities administered to the two groups were very similar. After 4 years of follow-up, 4% of patients were cured, 3% had biochemical disease and 93% had structural disease. However, 91% of patients obtained a clinical benefit from this therapy in terms of stabilization of the disease or complete remission or partial response. When considering the two groups separately, we did not find any difference in their outcome. When considering the response to 131-I therapy of the single type of metastases, 8% of lymph node metastases and 8% of lung metastases disappeared but none of the bone metastases. The response to 131-I therapy of the single type of metastases was similar when we looked at the two groups separately. This study shows (i) an overall clinical benefit of the 131-I therapy, since the majority of patients remained affected but with a stable disease, and (ii) that the preparation with either recombinant or endogenous TSH has no impact on the 131-I therapy efficacy and the outcome of our two groups of patients.

Radioiodine-131 therapy (RIT) in benign thyroid diseases: Personalized prescription based on objectives with optional use of pharmacological modulators

131I therapy (RIT) in benign thyroid diseases is the oldest and most currently used application of internal radiotherapy. With the new molecular 123I-TS images one may identify 15 presentations that can benefit from RIT. With three groups of activity determination corresponding to a dozen approaching protocols, several judgmental criteria (eu-, hypo-, hyperthyroidism, relapses etc.) and varying timeframes to assess the success, a “best method of activity calculation” makes little sense. Four clinical objectives must be first identified (goal): antitoxic (euthyroidism), ablative (hypothyroidism), reductive (to reduce a targeted volume) and preventive (to prevent progression from compensated to overt hyperthyroidism) 131I-RIT. A dose response relationship as regards the target volume reduction is firmly established in the short term (1-year) and explains the clinical outcome in Thyroid Functional Autonomy (TFA). In Grave's disease (GD), other factors may interfere that make the long-term function less predictable. Pharmacological modulators of 131I-RIT such as antithyroid drugs (ATDs) and LT3 must be skillfully handled. ATDs interfere with iodine kinetics, enhance the heterogeneity of the spatial dose deposition and diminish the accuracy of absorbed dose deposition, especially when using poorly controlled dosimetric approaches. Short LT3 administration suppresses TSH that allows direct targeting of the autonomously functioning thyroid tissue. The three main groups and variants of activity calculation are presented in detail. Calculating the activity allows a 50% average reduction in the 131I administered dose. Medical strategy should favour the informed patient's choice, after excluding the rare medical causes prompting discussion of an ablative approach. In TFA, low occurrence of hypothyroidism is the rule provided the treatment be given with a TSH<0.1mU/L, spontaneously or after LT3 suppression (compensated variety). In GD a long-term remission is rare (<30%) and should be thoroughly discussed since it leads to euthyroidism in approximately 50% after a 12-year follow-up. Depending on the etiology (GD/TFA) and the 4 clinical goals, 131I RIT planning is presented with optional choice of a patient adapted method of activity calculation and appropriate management of pharmacological modulators.

Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials.

A potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.

Micronuclei Formation upon Radioiodine Therapy for Well-Differentiated Thyroid Cancer: The Influence of DNA Repair Genes Variants.

Radioiodine therapy with 131I remains the mainstay of standard treatment for well-differentiated thyroid cancer (DTC). Prognosis is good but concern exists that 131I-emitted ionizing radiation may induce double-strand breaks in extra-thyroidal tissues, increasing the risk of secondary malignancies. We, therefore, sought to evaluate the induction and 2-year persistence of micronuclei (MN) in lymphocytes from 26 131I-treated DTC patients and the potential impact of nine homologous recombination (HR), non-homologous end-joining (NHEJ), and mismatch repair (MMR) polymorphisms on MN levels. MN frequency was determined by the cytokinesis-blocked micronucleus assay while genotyping was performed through pre-designed TaqMan® Assays or conventional PCR-restriction fragment length polymorphism (RFLP). MN levels increased significantly one month after therapy and remained persistently higher than baseline for 2 years. A marked reduction in lymphocyte proliferation capacity was also apparent 2 years after therapy. MLH1 rs1799977 was associated with MN frequency (absolute or net variation) one month after therapy, in two independent groups. Significant associations were also observed for MSH3 rs26279, MSH4 rs5745325, NBN rs1805794, and tumor histotype. Overall, our results suggest that 131I therapy may pose a long-term challenge to cells other than thyrocytes and that the individual genetic profile may influence 131I sensitivity, hence its risk-benefit ratio. Further studies are warranted to confirm the potential utility of these single nucleotide polymorphisms (SNPs) as radiogenomic biomarkers in the personalization of radioiodine therapy.

Can we safely reduce the administration of 131-iodine in patients with differentiated thyroid cancer? \u2013 experience of the Brugmann hospital in Brussels

Background131-iodine (131I) administration after surgery remains a standard practice in differentiated thyroid cancer (DTC). In 2014, the American Thyroid Association presented new guidelines for the staging and management of DTC, including no systematic 131I in patients at low-risk of recurrence and a reduced 131I activity in intermediate risk.The present study aims at evaluating the rate of response to treatment following this new therapeutic management compared to our previous treatment strategy in patients with DTC of different risks of recurrence.MethodsPatients treated and followed up for DTC according to the 2014-ATA guidelines (Group 2) were compared to those treated between 2007 and 2014 (Group 1) in terms of general characteristics, risk of recurrence (based on the 2015-ATA recommendations), preparation to 131I administration, cumulative administered 131I activity and response to treatment.ResultsIn total, 136 patients were included: 78 in Group 1 and 58 in Group 2. The two groups were not statistically different in terms of clinical characteristics nor risk stratification: 42.3% in Group 1 and 31% in Group 2 were classified as low risk, 38.5 and 48.3% as intermediate risk and 19.2 and 20.7% as high risk (P = 0.38). Two patients (one in each group) with distant metastases were excluded from the analysis.Preparation to 131I administration consisted in rhTSH stimulation in 23.4% of the patients in Group 1 and 100% in Group 2 (p < 0.001).131I was administered to 46/77 patients (59.7%) in Group 1 (5 at low risk of recurrence) and 38/57 patients (66.7%) in Group 2 (0 with a low risk). Among the patients treated by 131I, median cumulative activity was significantly higher in Group 1 (3.70GBq [100 mCi] range 1.11–11.1 GBq [30–300 mCi]) than in Group 2 (1.11 GBq [30 mCi], range 1.11–7.4 GBq [30–200 mCi], P < 0.001). Complete response was found in 90.9% in Group 1 vs. 96.5% in Group 2 (P = 0.20).ConclusionsUsing the 2015-ATA evidence-based guidelines for the management of DTC, meaning no 131I administration in low-risk patients, a low activity in intermediate and even high risk patients, and a systematic use of rhTSH stimulation before 131I therapy allowed us to reduce significantly the median administered 131I activity, with a similar rate of complete therapeutic response.

ANALYSIS OF THE SALIVARY BIOCHEMISTRY OF TWO PATIENTS AFTER RADIOIODINE TREATMENT

Introduction: Salivary gland damage such as xerostomia and sialadenitis is one of the most frustrating complications after radioactive iodine (131I) therapy. Objective: This study aimed to evaluate salivary flow rate, pH, and salivary composition in patients exposed to 131I. Study Design: Two patients diagnosed with thyroid carcinoma had total thyroidectomy and 131I exposure in 2013 and 2015, respectively, and were evaluated by unstimulated whole saliva (UWS). After collection, the sample was weighted and the salivary flow rate was calculated. The pH analysis was determined by means of Digimed 2-D portable pH meter, total protein concentration in the saliva was assessed by the Lowry method, and amylase was determined by the Bellavia method. Results: The doses of radioiodine were 118.8 mCi for patient 1 and 152.3 mCi for patient 2. Regarding salivary pH, patient 1 was at 6.9 and patient 2 at 6.2. Total protein and alpha amylase was (15 000 ug/mL and 2870 mg/mL ) in patient 1 and (10.78 ug/mL and 2377 mg/mL) in patient 2. When comparing healthy saliva to the saliva after 131I, a significant decrease was noted in all parameters. Patients exposed to 131I present with salivary alterations even after years of treatment, which has an effect on their quality of life. Introduction: Salivary gland damage such as xerostomia and sialadenitis is one of the most frustrating complications after radioactive iodine (131I) therapy. Objective: This study aimed to evaluate salivary flow rate, pH, and salivary composition in patients exposed to 131I. Study Design: Two patients diagnosed with thyroid carcinoma had total thyroidectomy and 131I exposure in 2013 and 2015, respectively, and were evaluated by unstimulated whole saliva (UWS). After collection, the sample was weighted and the salivary flow rate was calculated. The pH analysis was determined by means of Digimed 2-D portable pH meter, total protein concentration in the saliva was assessed by the Lowry method, and amylase was determined by the Bellavia method. Results: The doses of radioiodine were 118.8 mCi for patient 1 and 152.3 mCi for patient 2. Regarding salivary pH, patient 1 was at 6.9 and patient 2 at 6.2. Total protein and alpha amylase was (15 000 ug/mL and 2870 mg/mL ) in patient 1 and (10.78 ug/mL and 2377 mg/mL) in patient 2. When comparing healthy saliva to the saliva after 131I, a significant decrease was noted in all parameters. Patients exposed to 131I present with salivary alterations even after years of treatment, which has an effect on their quality of life.

Targeting poor proteasomal function with radioiodine eliminates CT26 colon cancer stem cells resistant to bortezomib therapy

We tested the hypothesis that tumor response to conventional bortezomib (BTZ) treatment is enhanced by targeted radiotherapy of resistant cancer stem cells (CSCs) that have characteristically poor proteasome function. This was accomplished by augmenting 131I uptake through expression of a sodium-iodide symporter (NIS) fusion protein that accumulates in cells with low proteasome activity. The NIS gene fused with the C-terminal of ornithine decarboxylase degron (NIS-cODC) was cloned. Stably expressing CT26/NIS-cODC cells and tumorsphere-derived CSCs were evaluated for NIS expression and radioiodine uptake. CT26/NIS-cODC cells implanted into mice underwent PET imaging, and tumor-bearing mice were treated with BTZ alone or with BTZ plus 131I. CT26/NIS-cODC cells accumulated NIS protein, which led to high radioiodine uptake when proteasome activity was inhibited or after enrichment for stemness. The cell population that survived BTZ treatment was enriched with CSCs that were susceptible to 131I treatment, which suppressed stemness features. Positron emission tomography and uptake measurements confirmed high 124I and 131I uptake of CT26/NIS-cODC CSCs implanted in living mice. In CT26/NIS-cODC tumor-bearing mice, whereas BTZ treatment modestly retarded tumor growth and increased stemness markers, combining 131I therapy suppressed stemness features and achieved greater antitumor effects. The NIS-cODC system offer radioiodine-targeted elimination of CSCs that are tolerant to proteasome inhibition therapy.