Synthesis, Screening, and Evaluation of Theranostic Molecular CPCR4-Based Probe Targeting CXCR4.

Chemokines and chemokine receptors are indispensable to play a key role in the development of malignant tumors. As one of the most widely expressed chemokine receptors, chemokine (C-X-C motif) receptor 4 (CXCR4) has been a popular research focus. In most tumors, CXCR4 expression is significantly upregulated. Moreover, integrated nuclide diagnosis and therapy targeting CXCR4 show great potential. [68Ga]Ga-pentixafor, a radioligand targeting CXCR4, exhibits a strong affinity for CXCR4 both in vivo and in vitro. However, [177Lu]Lu-pentixather, the therapeutic companion of [68Ga]Ga-pentixafor, requires significant refinement to mitigate its pronounced hepatic biodistribution. The objective of this study was to synthesize theranostic molecular tracers with superior CXCR4 targeting functions. The Daudi cell line, which highly expressed CXCR4, and the MM.1S cell line, which weakly expressed CXCR4, were used in this study. Based on the pharmacophore cyclo (-d-Tyr-n-me-d-Orn-l-Arg-L-2-NAL-Gly-) (CPCR4) of pentixafor, six tracers were synthesized: [124I]I-1 ([124I]I-CPCR4), [99mTc]Tc-2 ([99mTc]Tc-HYNIC-CPCR4), [124I]I-3 ([124I]I-pentixafor), [18F]AlF-4 ([18F]AlF-NETA-CPCR4), [99mTc]Tc-5 ([99mTc]Tc-MAG3-CPCR4) and [124I]I-6 ([124I]I-pentixafor-Ga) and their radiochemical purities were all higher than 95%. After positron emission tomography (PET)/single-photon emission computed tomography (SPECT) imaging, the [124I]I-6 group exhibited the best target-nontarget ratio. At the same time, comparing the [68Ga]Ga-pentixafor group with the [124I]I-6 group, we found that the [124I]I-6 group had a better target-nontarget ratio and lower uptake in nontarget organs. Therefore, compound 6 was selected for therapeutic radionuclide (131I) labeling, and the tumor-bearing animal models were treated with [131I]I-6. The volume of the tumor site was significantly reduced in the treatment group compared with the control group, and no significant side effects were found. [124I]I-6 and [131I]I-6 showed excellent affinity for targeting CXCR4, and they showed great potential for the integrated diagnosis and treatment of tumors with high CXCR4 expression.

Cytotoxicity Enhancement in Osteosarcoma with Multifunctional I-131 Radiotherapeutic Nanoparticles: In Vitro Three-Dimensional Spheroid Model and Release Kinetics Modeling.

This novel radiolabeled chitosan nanoparticle, facilitated with curcumin, increased doxorubicin cytotoxicity and radiosensitivity to MG-63 osteosarcoma cells in a three-dimensional model. Delivery of the anti-epidermal growth factor receptor (EGFR) targeted carboxymethyl chitosan nanoparticles, directly labeled with Na131I (ICED-N), achieved deep tumor penetration in a three-dimensional model. Of three kinetic models, the Higuchi model more closely matched the experimental curve and release profiles. The anti-EGFR targeting resulted in a 513-fold greater targeting efficacy to MG-63 (EGFR+) cells than the control fibroblast (EGFR-) cells. The curcumin-enhanced ICED-N (4 × 0.925 MBq) fractionated-dose regime achieved an 18.3-fold increase in cell cytotoxicity compared to the single-dose (1 × 3.70 MBq) doxorubicin-loaded nanoparticle, and a 13.6-fold increase in cell cytotoxicity compared to the single-dose Na131I nanoparticle. Moreover, the ICED-N fractionated dose increased cells in the G2/M phase 8.78-fold, indicating the cell cycle arrest in the G2/M phase is associated with DNA fragmentation, and the intracellular damage is unable to be repaired. Overall, the results indicate that the fractionated dose was more efficacious than a single dose, and curcumin substantially increased doxorubicin cytotoxicity and amplified osteosarcoma cell radiosensitivity to Na131I.

Update on lacrimal apparatus dysfunction associated with differentiated thyroid cancer after I-131 therapy.

PURPOSE: The most prevalent lacrimal apparatus dysfunctions associated with differentiated thyroid cancer(DTC) after I-131 therapy are dry eye and nasolacrimal duct obstruction(NLDO), leading to ocular discomfort and lower quality of life for patients. It is crucial to diagnose and manage lacrimal apparatus dysfunction associated with I-131 therapy for DTC. Therefore, this review aims to comprehensively summarize and analyze the advances in mechanisms and therapeutic options underlying lacrimal apparatus dysfunction induced by I-131 therapy for DTC. METHODS: A comprehensive search of CNKI, PubMed, and Wed of Science was performed from the database to December of 2023. Key search terms were "Thyroid cancer", "I-131", "Complications", "Dry eye", "Epiphora", "Tear", "Nasolacrimal duct" and "NLDO". RESULTS: The research indicates that I-131 therapy for DTC causes damage to the lacrimal glands and nasolacrimal duct system, resulting in symptoms such as dry eye, epiphora, and mucoid secretions. Moreover, recent research has focused on exploring relevant risk factors of the condition and experimental and clinical treatments. However, there is some controversy regarding the mechanisms involved, whether it is due to the passive flow of I-131 in tears, active uptake of I-131 by the sodium-iodide symporter (NIS) in the lacrimal sac and nasolacrimal duct, or secondary metabolic and hormonal disturbances caused by I-131. CONCLUSION: It is crucial for early detection and preventive measures by ophthalmologists and the need for further studies to elucidate the mechanisms underlying the disease.

Clinical conditions related to positive thymic uptake on I-131 post-therapeutic scans in thyroid cancer patients.

OBJECTIVE: Thymic uptake is a well-known cause of false-positives on I-131 post-therapeutic scans. This study identified the clinical conditions associated with thymic uptake on I-131 post-therapeutic scans in thyroid cancer patients. DESIGN: This was a retrospective study that investigated the clinical conditions associated with thymic uptake on I-131 post-therapeutic scans of patients obtained between January 2010 and December 2010. PATIENTS: Six hundred and eighty-five patients were included follwing a therapeutic dose of I-131 (3.7-9.25 GBq). METHODS: We reviewed the patients' clinical characteristics, including age, sex, histology, serum thyrotropin (TSH) stimulation regimen, prior history of RAI therapy, and labaratory parameters such as the serumTSH, thyroglobulin, and anti-thyroglobulin antibody. At follow-up, patients were assessed in terms of disease-free status, structural persistence, and biochemical disease. RESULTS: In total, 107 I-131 post-therapeutic scans (15.6%) evidenced thymic uptake. The mean age of the positive thymic uptake group was significantly lower than that of the negative group (p < .001). Significant indicators for thymic uptake were thyroid hormone withdrawal and a history of repeated radioactive iodine (RAI) therapy (p < .05). Logistic regression analysis showed that young age and a history of repeated RAI therapy correlated with thymic uptake (p < .001). At the end of follow-up, 487 patients (86.5%) were disease-free, 44 (7.8%) still had biochemical disease, and 32 (5.7%) showed structural persistence. Ten patients (11.5%) in the positive thymic uptake group and 22 (4.6%) in the negative thymic uptake group showed structural persistence. Five patients (5.7%) in the positive thymic uptake group and 39 (8.2%) in the negative thymic uptake group had biochemical disease. The final follow-up results of the two groups were statistically different. CONCLUSIONS: Thymic uptake tended to be more prominent in young patients with a history of repeated RAI therapy. Structural recurrence during follow-up was much more common in the positive thymic uptake group, while the incidence of biochemical recurrence during follow-up was higher in the negative thymic uptake group.

Chronic Myeloid Leukemia following Exposure to Radioactive Iodine (I131): A Systematic Review.

BACKGROUND: Therapy-related leukemia is a term that describes the occurrence of leukemia following exposure to hematotoxins and radiation to emphasize the difference from leukemia that arises de novo. Many agents and host factors contribute to this entity of leukemias. Therapy-related acute myeloid leukemia has an extensive literature review in contrast to therapy-related chronic myeloid leukemia (t-CML). Radioactive iodine (RAI), an established agent in the management of differentiated thyroid carcinomas, has raised concern due to its possible carcinogenic effects. SUMMARY: In this article, we reviewed all the reports from the 1960s to date related to t-CML following RAI on Google Scholar and PubMed. We have identified 14 reports and found that most reports were for men under the age of 60 years with primary papillary thyroid carcinoma and mixed follicular-papillary thyroid carcinoma who developed t-CML mainly between 4 and 7 years after exposure to varying doses of I131. However, the mean dose was 287.78 millicuries (mCi). It was reported that a statistically significant increase in leukemia following RAI therapy (relative risk of 2.5 for I131 vs. no I131). Also, there was a linear relationship between the cumulative dose of I131 and the risk of leukemia. Doses higher than 100 mCi were associated with a greater risk of developing secondary leukemia, and most of the leukemias developed within the initial 10 years of exposure. The precise mechanism through which RAI provokes leukemia is largely unclear. A few mechanisms have been proposed. KEY MESSAGES: Although the risk for t-CML appears to be low based on current reports and does not represent a contraindication to RAI therapy, it should not be disregarded. We suggest including it in the risk-benefit discussion before initiating this therapy. Long-term follow-up for patients is advisable for those who received doses over 100 mCi with a complete blood count, possibly yearly, for the first 10 years. The new onset of significant leukocytosis post RAI exposure should raise the suspicion for t-CML. Further studies are needed to establish or refute a causal relationship.

Radiological study of a wastewater treatment plant associated with radioiodine therapy at a hospital in West Java, Indonesia.

Nuclear medicine (NM) services in Indonesia have rapidly developed due to the increasing number of patients, and this growth has been supported by standardized regulations in the field, including the management of solid waste generated. However, multiple reports indicate that licensing control does not regulate liquid waste disposal from patient excretions to protect personnel and the community from radiopharmaceutical exposure. One of the radiopharmaceuticals commonly used in NM and having the longest half-life among the radiopharmaceuticals used in NM is iodine 131(I-131). Thus, this study used a high-purity germanium detector to measure iodine-131 (I-131) activity in liquid waste from decay tanks, temporary collection channels, the hospital's wastewater treatment plant (WWTP) outlet, and six points around the NM service and liquid waste treatment unit. Concentration measurements in three decay tanks were carried out sequentially every 12 h for 3 d, corresponding to the therapy period. The results showed that the I-131 activity levels in the decay tanks and temporary collection channels, before being mixed with liquid waste from other units, were 95.9 × 106± 4.4 × 106Bq m-3.At the point where the liquid waste from other units was mixed, the activity level decreased significantly to 472 680 ± 22 160 Bq m-3, which was below the clearance level of 107Bq m-3. However, the recorded concentration exceeded the standard for environmental radioactivity at the hospital's WWTP outlet, namely 37 670 ± 2040 Bq m-3. The measurement results for I-131 in the air in the open space for two nuclear buildings was above the standard at 1.3 ± 0.27 Bq m-3. According to the RESRAD simulation, based on the initial dose taken from the liquid waste treatment outlet point, the accumulation of doses and the risk of cancer among workers and the community decreased within 3 months after the maximum exposure.

Outcomes of Radioactive Iodine (131I) Therapy among Hyperthyroid patients.

Objective: The present study aimed to assess the thyroid outcomes six-months after radioactive Iodine-131 therapy (RIT) among hyperthyroid patients and identify the factors associated with them. Methods: This retrospective observational study was conducted at the department of Nuclear Medicine and Molecular Imaging, Northwest General Hospital & Research Centre during 2013 to 2019. For the study purpose, the thyroid outcomes of 153 hyperthyroid patients were studied retrospectively for six months after RIT. The data was obtained from the medical records. Patient baseline characteristics, clinical features, laboratory investigations, results of thyroid imaging, and therapeutic investigations were acquired and recorded in a structured questionnaire. Results: Out of the 153 screened records of hyperthyroid patients, 19.6% became euthyroid, 9.2% remained hyperthyroid, and 25.5% developed hypothyroidism after six months of RIT. The observed remission rate by the end of six months was 80.95%. Three months post-RIT, gender and RAI doses had a significant effect on thyroid function. The frequency of hypothyroidism was higher among those treated with an RAI dose of ≤ 20 mCi (83.0%) than those treated with a higher dose > 20 mCi (17%). Moreover, most patients receiving > 20 mCi radioiodine became euthyroid (64.5%). Similar outcomes were observed after six months of the therapy, except gender was replaced by etiologies of hyperthyroidism (p=0.009). Conclusion: Radioactive iodine (131-I) therapy is effective for the treatment of hyperthyroidism. However, the appropriate dose is still debatable, as there was a high incidence of hypothyroidism post-therapy.

A NEW HYPOTHESIS IN THE TREATMENT OF RECURRENT GLIOBLASTOMA MULTIFORME (GBM). PART 2: IS THERE AN ALTERNATIVE THERAPY OPTION IN RECURRENT GM WHEN ALL STANDARD TREATMENTS HAVE BEEN EXHAUSTED?

Glioblastoma multiforme (GBM) is the most aggressive and malignant brain tumor. The average survival time for a patient diagnosed with GBM, using standard treatment methods, is several months. Besides the routinely applied treatments such as neurosurgery, radiotherapy, and chemotherapy, progress is being made in the field of oncology, offering hope for improved treatment outcomes. New treatment methods include individualized multimodal immunotherapy (IMI) and modulated electro-hyperthermia. The coauthor of the above series of articles (parts 1 and 2) - A.Cz. presents the concept of a new, potentially breakthrough treatment option for recurrent GBM. A.Cz. was diagnosed with GBM in August 2021. Exhaustion of standard treatment methods, as well as immunotherapy and virotherapy, only provided temporary relief. Unfortunately, after a few months, the disease recurred. Having little to lose, A.Cz. accepted an ablative dose of 2960 MBq (80 mCi) of I131, based on available literature data. Three days before the administration of radioiodine therapy (RIT), A.Cz. prophylactically blocked the thyroid's ability to absorb the radioisotope. In June 2023, approximately 7 weeks after receiving single I131 dose, the MRI examination confirmed a 30% reduction in the tumor's size. Based on this, one can speculate that Iodine-131 therapy may be an alternative treatment option for GBM patients in the future. However, this hypothesis requires confirmation in further clinical studies.

Changes in Radiosensitivity to Gamma-Rays of Lymphocytes from Hyperthyroid Patients Treated with I-131.

This study investigated the peripheral blood lymphocytes (PBL) response to a dose of γ-rays in patients treated with radioiodine (I-131) for hyperthyroidism vs. healthy controls, to gain information about the individual lymphocytes' radio-sensitivity. Blood samples were taken from 18 patients and 10 healthy donors. Phosphorylated histone variant H2AX (γ-H2AX) and micronuclei (MN) induction were used to determine the change in PBL radio-sensitivity and the correlations between the two types of damage. The two assays showed large inter-individual variability in PBL background damage and in radio-sensitivity (patients vs. healthy donors). In particular, they showed an increased radio-sensitivity in 36% and 33% of patients, decrease in 36% and 44%, respectively. There was a scarce correlation between the two assays and no dependence on age or gender. A significant association was found between high radio-sensitivity conditions and induced hypothyroidism. PBL radio-sensitivity in the patient group was not significantly affected by treatment with I-131, whereas there were significant changes inter-individually. The association found between clinical response and PBL radio-sensitivity suggests that the latter could be used in view of the development of personalized treatments.

Recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal preparation for radioiodine ablation in differentiated thyroid cancer in children, adolescents and young adults.

OBJECTIVE: Recombinant human TSH (rhTSH) is commonly used to prepare patients for postoperative radioiodine (I-131) ablation after surgery for differentiated thyroid cancer (DTC). In adults, rhTSH is associated with equivalent oncologic efficacy in comparison to thyroid hormone withdrawal (THW), but its use has not been well studied in children. We aimed to measure time to disease progression after rhTSH stimulation vs. THW in paediatric patients under the age of 21 with DTC following total thyroidectomy. DESIGN: Retrospective cohort study (March 2001-July 2018). PATIENTS: Sixteen children and adolescents (75% female, median age, 17.4 years) who received rhTSH were compared to 29 historical controls (72% female, median age, 18.5 years) prepared with THW, followed for a median of 2.4 years (range, 0.5-14). MEASUREMENTS: Stimulated serum TSH concentrations prior to I-131 ablation and time to disease progression, as determined by a component outcome variable encompassing both structural and biochemical disease persistence/recurrence. RESULTS: No differences were observed in tumour characteristics and I-131 dose (median 2.3 [1.8-2.90] mCi/kg rhTSH) between groups. Patients who received rhTSH achieved a similar median stimulated TSH level (163 [127-184] mU/L), compared to those who underwent THW (136 [94.5-197] mU/L; p = .20). Both groups exhibited similar time to progression (p = .13) and disease persistence/recurrence rates (rhTSH 31% vs. THW 59%, p = .14). CONCLUSION: In this cohort of children and adolescents with DTC, we observed similar time to disease progression among those who received rhTSH or underwent THW prior to postoperative I-131 ablation.

Success rate of radioactive iodine treatment for children and adolescent with hyperthyroidism.

PURPOSE: To assess the success rate of first dose radioiodine for treatment of hyperthyroidism in children and adolescent. METHODS: This is a retrospective data analysis of children and adolescent with hyperthyroidism who received radioiodine (RAI) therapy from January 2013 to December 2017. Age, gender, family history of hyperthyroidism, duration of anti-thyriod drugs (ATDs) treatment, rapid turnover status, 2 h and 24 h I-131 radioiodine uptake (RAIU), thyroid volume, and treatment dose were also analyzed. The goal of RAI therapy was to achieve hypothyroidism within 3-6 months after treatment. Treatment result was evaluated at 6 months after treatment and divided into 2 groups: treatment success (hypothyroid and euthyroid) and treatment failure (hyperthyroid). The same parameters were compared between both groups. RESULTS: 32 hyperthyroid patients, 26 female with mean age at treatment of 13.84 ± 1.83 years. All patients had prior treatment with ATDs, with a median treatment duration of 32.5 months (range 2-108). The median estimated thyroid gland size was 24.62 g, range 9.29-72.8. RAI doses ranged from 4.1 to 29.9 mCi (median dose = 7.54 mCi). Significant difference in 24-h I-131 uptake and RI status was demonstrated. Successful treatment rate after single dose of therapeutic I-131 was 65.63%. CONCLUSION: With the I-131 dose of 220 µCi/g of thyroid tissue, successful treatment rate after single dose of therapeutic I-131 was 65.63%. RAI therapy with I-131 dose of 250-400 µCi/g of thyroid tissue might be suitable in patients with medical failure from ATDs. Possible role of RI as the predictor for RAI therapy failure are needed to investigate in both adult and children clinical settings.

Differentiated thyroid cancer patients potentially benefitting from postoperative I-131 therapy: a review of the literature of the past decade.

BACKGROUND: Since the last major review of literature on the benefit of I-131 therapy, the continued debate on postoperative radioiodine treatment (RIT) in differentiated thyroid carcinoma (DTC) has led to a number of further studies being published on this topic. AIM: The aim of the present paper is to report the results of an updated structured review of the literature pertaining to the prognostic benefits of postoperative RIT in DTC in terms of recurrence-free and disease-specific survival. METHODS: A systematic search of the literature was performed using the Medline and Cochrane Library database. The search period started in August 2007 and ended on December 6, 2017. Search terms used included "differentiated thyroid cancer" and "radioiodine therapy" amended by specific terms for recurrence/disease-free survival or overall and/or cancer-specific survival. Included in the search were systematic reviews, randomized clinical trials, or cohort studies consisting of both patients who underwent postoperative RIT and patients treated by surgery alone. RESULTS: Eleven retrospective cohort studies met the defined inclusion criteria and were included in the present review. Results of the studies were mixed, with some showing a benefit of RIT even in microcarcinoma whereas others showed no benefit at all. CONCLUSION: Literature published in the last decade offers data that support adjuvant postoperative RIT in DTC patients with a tumor diameter exceeding 1 cm. Therefore, at least until randomized prospective studies prove otherwise, the prescription of adjuvant I-131 treatment to all DTC patients with a primary tumor diameter exceeding 1 cm remains a reasonable option.

Radioactive Iodine Therapy in Differentiated Thyroid Cancer: 2020 Update.

OBJECTIVE. The paradigm of theranostics is based on tailoring therapy for the purpose of optimizing outcomes. This principle is being applied to radioactive iodine therapy. Consequently, thyroid cancer therapy protocols are evolving. The purpose of this article is to promote a modern approach to radioiodine therapy. CONCLUSION. This article highlights guidelines and position statements, summarizes the prognostication systems of thyroid cancer, and reviews which prescribed activities of 131I.

Radioiodine treatment for graves' disease: a 10-year Australian cohort study.

BACKGROUND: Radioactive iodine (I131) is a common definitive treatment for Graves' Disease. Potential complications include worsening, or new development of Graves' eye disease and development of a radiation thyroiditis. The purpose of the present study was to assess outcomes of patients treated with I131 in an Australian tertiary centre over 10 years. METHODS: Data from 101 consecutive patients treated with I131 for a diagnosis of Graves' disease between 2005 to 2015 was collected and reviewed retrospectively. Baseline TSH receptor antibody titre, pre-treatment free thyroxine (FT4), technetium scan uptake, initial treatment, duration of treatment, reason for definitive therapy, complications, and time to remission (defined as euthyroidism or hypothyroidism after 12 months) were recorded. RESULTS: Of the 92 patients with adequate outcome data, 73 (79.3%) patients achieved remission with a single dose of I131. Of the remaining 19 patients, 12 had a second dose and became hypothyroid. TSH receptor antibody titre at diagnosis was significantly lower in the group that achieved remission with the first dose compared with those who did not (P = 0.0071). There was no difference in technetium uptake, I131 dose, duration of therapy or pre-treatment free thyroxine (FT4). I131 was complicated by development of eye disease in 3 patients and 1 (of 11 with pre-existing eye disease) had worsening eye disease. A clinically apparent flare of hyperthyroidism following I131 was evident in 8 patients (8.6%). CONCLUSION: Radioiodine is an effective therapy for Graves' Disease with few complications. The majority of patients achieve remission with a single dose. Those who require a second dose are more likely to have higher TSH receptor antibody titres at diagnosis. To the best of our knowledge, this is the first study to report outcomes from radioiodine treatment for Graves' disease in an Australian population.

Measuring the actual I-131 thyroid uptake curve with a collar detector system: a feasibility study.

Radionuclide therapy using I-131 is commonly used for the treatment of benign thyroid diseases. The therapeutic dose to be administered is calculated based on the type of disease, the volume of the thyroid, and the measured uptake percentage. This methodology assumes a similar biological half-life of iodine, whereas in reality a large variation in biological half-life is observed. More knowledge about the actual biological half-life of iodine for individual patients will improve the quantification of the delivered radiation dose during radioiodine therapy and could aid the evaluation of the success of the therapy. In this feasibility study we used a novel measurement device [Collar Therapy Indicator (CoTI)] to measure the uptake curve of patients undergoing I-131 radioiodine therapy. The CoTI device is a light-weight wearable device that contains two independent gamma radiation detectors that are placed in a collar. By comparing results of thyroid uptake measurements with results obtained with a gamma camera, the precision of the system is demonstrated. Additionally, for three patients the uptake curve is measured during 48 h of admission in the hospital. The presented results demonstrate the feasibility of the new measurement device to measure the uptake curve during radioiodine therapy.

Early and late adverse effects of radioiodine for pediatric differentiated thyroid cancer.

BACKGROUND: Radioiodine-131 (I131) therapy for differentiated thyroid cancer (DTC) is generally a safe and effective treatment, but it has some potential side effects, which have been well described in adults but less analyzed in children. Our aim was to describe early and late adverse events of radioactive I131 in pediatric patients. METHODS: All consecutive patients ≤18 years treated for DTC in the period 1980-2015 were retrospectively analyzed for early and late side effects of radioiodine. Early side effects include nausea/emesis, radiation thyroiditis, sialadenitis, dry mouth, and transient bone marrow (BM) suppression. Late complications include permanent salivary gland dysfunction, permanent BM suppression, pulmonary fibrosis, second cancers, and fertility problems. RESULTS: One hundred five pediatric patients were treated with I131 for DTC in our department for a total amount of 302 radioiodine treatments. In total, 127 early complications were recorded: 44 episodes of nausea/emesis; 30 sialoadenitis, 24 thyroiditis, 18 dry mouth, and 11 transient BM suppression. Early side effects were correlated with the amount of radioactivity administered in any treatment. Twelve children developed ≥1 late complication for a total of 20 complications: two permanent salivary gland dysfunction, four permanent BM suppression, five pulmonary fibrosis, four second malignancies, and five fertility alterations. Late events, except fertility alterations, were correlated with the number of therapies and cumulative activities of I131. CONCLUSIONS: In conclusion, early side effects of I131 are associated with the amount of administrated activities of each treatment, while the late effects are correlated with the number of treatments and cumulative activities of radioiodine, except for fertility problems.

Incidence of Hypothyreoidism after Radioactive Iodine-I131 Treatment in Dependance of Hyperthyreoidism Etiology and Therapy Dose.

INTRODUCTION: Consensus hasn't been yet achieved about optimal dose quantity that could prevent post therapy hypothyroidism, thus dosing approach varies among different centers. I131 doses can be fixed or calculated, although treatment outcomes don't differ significantly according to recent acknowledgments. AIM: Determination of the incidence of hypothyroidism after radioiodine treatment (I131) in dependence of hyperthyroidism etiology and quantity of applied doses. MATERIALS AND METHODS: The study included 100 patients which have had radioiodine treatment, with a three year post-treatment follow up. The study was conducted at the Nuclear Medicine Department, University Clinical Center of Sarajevo. Data were provided from the patient medical histories. Research is designed as a retrospective, descriptive study. All data were analyzed using Microsoft Excel and the statistical program SPSS 13.0. RESULTS: After the three year follow up, incidence of hypothyroidism within patients with Graves' disease was 89.5%, with diffuse goiter 50%, with toxic adenoma (TA) 26.8%, and with multinodulare goitre (MNG) 57.1%. Hypothyreoidism in patients with diffuse goiter, Graves' disease and TA was mostly developed after I131 therapy with a dose quantity of 10.1-15 mCi and in MNG patients after RAI therapy with applied doses of 15.1-20 mCi. CONCLUSION: The hypothyroidism incidence rate is the highest among patients with Graves' diseases and the lowest among the TA patients. It's mostly developed after dose quantity of 10.1-15mCi and it is rare at dose quantity less than 5mCi. 50% of hypothyroidism were developed among patients with diffuse goiter, Graves'disease.

Long-term outcomes of (131)Iodine mIBG therapy in metastatic gastrointestinal pancreatic neuroendocrine tumours: single administration predicts non-responders.

BACKGROUND: (131)Iodine (I131)-metaiodobenzylguanidine (mIBG) is a radionuclide-based treatment option for metastatic gastrointestinal-pancreatic neuroendocrine tumours (GEP NET). This study aimed at identifying prognostic indicators of long-term outcome based on initial evaluation following a first mIBG treatment (7400 MBq) in a patient cohort with such tumours, with a secondary aim of evaluating progression-free survival (PFS) and overall survival (OS) following mIBG therapy. METHODS: Retrospective review of the hospital records was performed to identify a cohort of 38 adult patients who underwent (131)Iodine-mIBG therapy over a 9-year period for metastatic GEP NETs and neuroendocrine tumours with an unknown primary. Treatment response was evaluated based on radiological criteria (RECIST1.1), biochemical markers [serum Chromogranin A (CgA)/urinary 5HIAA] and symptomatic response at clinical follow-up, all evaluated at 3-6 months from first mIBG treatment. Progression-free survival (PFS) and overall survival (OS) from the first mIBG treatment were recorded. RESULTS: At 3-6 months following a single mIBG therapy, 75%, 67%, and 63% of patients showed either a partial response (PR) or stable disease (SD) on radiological, biochemical, and symptomatic criteria, respectively. Complete response (CR) was not seen in any patient. OS from the date of diagnosis and from the first therapy was 8 years +/-1.1 (95% CI 5.7 to 10.2 years) and 4 years+/-0.69 (95% CI 2.6-5.3 years), respectively. Twenty-nine percent of patients were alive at 10 years. Significant survival advantage was seen in patients with SD/PR as compared to those who had progressive disease (PD) for each of these three criteria. CONCLUSION: Biochemical, radiological (RECIST 1.1) and symptomatic assessment of disease status at 3 to 6 months after first I131-mIBG therapy stratifies patients with a poor prognosis. This can be used to identify patients who may benefit from alternative strategies of treatment.

Streamlining the imaging of clinically suspected pheochromocytoma: using urine metanephrines to decrease imaging costs.

PURPOSE: To improve the cost efficiency of the imaging evaluation of clinically suspected pheochromocytoma by using 24-hour fractionated urine metanephrine (FUM) results. METHODS: A retrospective review of I-123 meta-iodo-benzyl-guanidine single photon emission tomography (SPECT) computed tomography (CT) studies performed at our institution between January 2007 and February 2011 for clinically suspected pheochromocytoma was performed. SPECT-CT results from 70 patients were compared with results from 24-hour FUM analysis (within 2 months of SPECT-CT) and with relevant CT or magnetic resonance imaging studies (within 6 months of SPECT-CT). An imaging algorithm was developed to maximize cost efficiency without altering the final imaging interpretation. Actual imaging costs for the studied cohort were compared with the expected costs if this algorithm had been applied. RESULTS: If the 24-hour FUMs were normal, then all the SPECT-CT studies were negative (16/70). Eighty-seven percent of patients with abnormal total metanephrine had a positive SPECT-CT. If the total metanephrine was normal but 1 or more of the metanephrine fractions were abnormal, then 39%-58% of the SPECT-CT studies were positive. Within this subgroup, none had a positive SPECT-CT if a CT or magnetic resonance image was negative or benign. The actual imaging costs averaged CAD$2833.19 per patient for this cohort. Applying a streamlined imaging algorithm guided by 24-hour FUM analysis would result in an average imaging cost of CAD$1225.97 per patient without an expected change in the final imaging impression. CONCLUSION: By using 24-hour FUM results to streamline imaging, considerable cost savings per patient (56.7%) can be attained without a change in the final overall imaging interpretation.

Correlation between remnant thyroid gland I-131 uptake and serum thyroglobulin levels: can we rely on I-131 whole body scans?

BACKGROUND: I-131 treatment (RAI) decision relies heavily on serum thyroglobulin (Tg) levels, as higher Tg levels are assumed to be correlated with higher I-131 uptake. Tg elevation, negative iodine scintigraphy (TENIS) definition is becoming more clinically relevant as alternative treatment methods are available. This study examined the correlation between Tg levels with I-131 uptake in remnant thyroid gland to evaluate the reliability of serum Tg levels in predicting I-131 uptake. METHODS: From March 2012 to July 2019, 281 papillary thyroid cancer patients treated with 150 mCi RAI were retrospectively enrolled. Early (2nd day) and Delayed (7th day) post-RAI whole-body scan (WBS) neck counts were correlated with clinical and pathologic findings. Patients with normal neck ultrasound and undetectable level of serum Tg (< 0.2 ng/mL) and thyroglobulin antibody (TgAb) (< 10 IU/mL) were defined as ablation success within 2 years after I-131 ablation. RESULTS: Thyroid gland weight, tumor size and thyroiditis were independent factors of preoperative serum Tg levels. Serum off-Tg levels correlated with Early and Delayed WBS neck counts, and thyroiditis pathology contributed to lower neck counts in both Early and Delayed WBSs. In multivariable analysis, Delayed WBS neck count, serum off-Tg and off-TgAb were significant factors for predicting ablation success. CONCLUSION: I-131 uptake and retention in remnant thyroid gland correlates with serum off-Tg levels, thyroiditis, and ablation success in thyroid cancer patients receiving high-dose I-131 therapy. Semi-quantitative I-131 analysis with Early and Delayed WBSs provides additional information in evaluating ablation success, with the potential application for metastasis treatment response evaluation.