131I Intake and Regulatory Compliance Following Administration of Capsular 131I Sodium Iodide for Treatment of Thyroid Disorders.

ABSTRACT: Intake of 131I by nuclear medicine technologists and physician Authorized Users was evaluated using bioassay data from administration of 131I sodium iodide in capsular form during a 5-year period. Maximum estimated annual intake of 131I sodium iodide, based on bioassay measurements performed at 24 hours post administration, ranged from 10.9 to 35.6 kBq for all staff. Intake by Authorized Users was higher than that by nuclear medicine technologists due to state requirement for Authorized Users to physically administer therapeutic dosages of radiopharmaceuticals. All intake values were less than 10% of the 131I thyroid ALI of 50 microcurie3 (1,850 kBq), indicating that monitoring may be discontinued for staff participating in routine administration of 131I capsules in which volatilization is not suspected. Elimination of bioassay performance has permitted more flexibility in patient scheduling and improved workflow and efficiency.

Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane-Sodium Iodide-Promoted Vorbrüggen Glycosylation.

By simple combination of water and sodium iodide (NaI) with chlorotrimethylsilane (TMSCl), promotion of a Vorbrüggen glycosylation en route to essential HIV drugs emtricitabine (FTC) and lamivudine (3TC) is achieved. TMSCl-NaI in wet solvent (0.1 M water) activates a 1,3-oxathiolanyl acetate donor for N-glycosylation of silylated cytosine derivatives, leading to cis-oxathiolane products with up to 95% yield and >20:1 dr. This telescoped sequence is followed by recrystallization and borohydride reduction, resulting in rapid synthesis of (±)-FTC/3TC from a tartrate diester.

El tratamiento paciente específico del hipertiroidismo con radioyodo: una oportunidad a la mejora / Radioiodine treatment of hyperthyroidism with patient-specific techniques: an improvement opportunity

Introducción: La aplicación de actividades fijas en el tratamiento del hipertiroidismo con I131 (yoduro de sodio, conocido también como radioyodo), es el método más usado en nuestro país, a pesar de la individualidad morfo-funcional que caracteriza esta afección. Sin embargo, no existe aún, un consenso internacional sobre la dosis más conveniente para cada caso, y por ende, los resultados no siempre son los deseados. Objetivo: Evaluar la aplicabilidad de varios métodos de cálculo de dosis paciente-específica para el tratamiento de hipertiroidismo con yoduro de sodio. Métodos: Se realizó un análisis de los resultados de varios métodos de cálculo de dosis recomendados internacionalmente a partir de la actividad fija prescrita en 10 pacientes, con el empleo de tecnologías y herramientas ya desarrolladas y disponibles en el país. Se evaluó la variabilidad inter-especialista y su impacto en la dosis planificada para el tratamiento. Resultados: El uso de la información incompleta de la biodistribución y farmacocinética del paciente produjo diferencias entre -42 por ciento y 37 por ciento de las dosis para el mismo paciente. El resultado de la comparación del método de cálculo recomendado por la Sociedad Europea de Medicina Nuclear, manejando la masa por gammagrafía-2D / 3D y por ultrasonido, arrojó diferencias no significativas entre sí. La variabilidad inter-especialista de las actividades prescrita mostró diferencias significativas, que arrojan sobre el mismo paciente, discrepancias entre 44Gy y 243Gy de las dosis terapéuticas a recibir, situación que puede comprometer el éxito del tratamiento y producir efectos secundarios no deseados. Conclusiones: Las técnicas dosimétricas paciente-específicas se pueden implementar satisfactoriamente en nuestro país. Las diferencias numéricas encontradas, especialmente la variabilidad inter-especialista, demuestran la no estandarización terapéutica, lo que apoya el uso de la farmacocinética paciente-específica pre terapéutica y la masa por gammagrafía-3D para planificar el tratamiento siempre que sean posible(AU)

Introduction: Despite of its typical morpho-functional individuality, fixed activities remain as the most used method in Cuba for hyperthyroidism treatment with I (sodium iodide, also known as radioiodine). However, there is not yet an international consensus on the most convenient doses for each case, so, the results are not always the desired ones. Objective: To evaluate the applicability of various patient-specific dose calculation methods for the treatment of hyperthyroidism with sodium iodide. Methods: It was carried out an analysis in 10 patients of the results of some methods for dose calculation from the prescribed fixed activity recommended internationally, with the use of technologies and tools already developed and available in the country. The inter-specialist variability and its impact in the planned dose for the treatment were assessed. Results: The use of uncompleted biodistribution and pharmacokinetics information of the patient showed differences between -42 percent and 37 percent in the doses for the same patient. The outcome of the comparison of the calculation method recommended by the European Society of Nuclear Medicine managing the mass by 3D/2D gammagraphy and ultrasound, presented no significant discrepancies among them. The inter-specialist variability of prescribed activity was statistically significant, and it can produce in the same patient differences between 44Gy and 243Gy of the therapeutic doses, which could affect the treatment success and lead to unnecessary side effects. Conclusions: The patient´s personalized calculation methods can be satisfactorily applied in Cuba. The numeric differences found, especially inter-specialist variability, show the lack of therapeutic standardization, which supports the use of pre-therapeutic patient-specific pharmacokinetics and the mass by 3D-gammagraphy to plan the treatment when possible(AU)

Analysis of activity uptake, effective half-life and time-integrated activity for low- and high-risk papillary thyroid cancer patients treated with 1.11 GBq and 3.7 GBq of 131I-NaI respectively.

PURPOSE: To analyse the activity uptakes, effective half-lives and time-integrated activities, of relevance for remnant dosimetry, for patients treated for papillary thyroid cancer (PTC) with a different amount of activity of 131I-NaI. METHODS: Fifty patients were included. Of those, 18 patients had low-risk PTC and were treated with 1.11 GBq of 131I-NaI (Group 1), and 32 patients had high-risk PTC and were treated with 3.7 GBq (Group 2). Radioiodine was administered after total thyroidectomy and rhTSH stimulation. Two SPECT/CT scans were performed for each patient to determine the remnant activities and effective half-lives. RESULTS: Significantly higher values (p < 0.05) were obtained for Group 1 for the remnant activity at 7 d (medians 1.4 MBq vs 0.27 MBq), the remnant activity per administered activity at 2 d (0.35% vs 0.09%) and at 7 d (0.13% vs 0.007%), and the effective half-life (93 h vs 40 h). Likewise, the time-integrated activity coefficient was significantly higher for Group 1. The time-integrated activity did not differ significantly between the two groups (p > 0.05). CONCLUSIONS: We found a significant difference in the remnant activity per administered activity, the rate of washout from thyroid remnants, and the time-integrated activity coefficient between low-risk PTC patients treated with 1.11 GBq and high-risk PTC patients treated with 3.7 GBq. On the contrary, there was no such difference in the time-integrated activity. If remnant masses were also not statistically different (reasonable assumption for this monocentric study) no difference in time-integrated activity would imply no difference in remnant absorbed dose, of relevance for treatment efficacy and the risks of stochastic effects.

Captación de yoduro sódico 131I en un teratoma ovárico / Radioactive iodine 131I uptake in an ovarian teratoma

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Radionuclide Therapies in Molecular Imaging and Precision Medicine.

This article reviews recent advances and applications of radionuclide therapy. Individualized precision medicine, new treatments, and the evolving role of radionuclide therapy are discussed.

Whole-remnant and maximum-voxel SPECT/CT dosimetry in 131I-NaI treatments of differentiated thyroid cancer.

PURPOSE: To investigate the possible differences between SPECT/CT based whole-remnant and maximum-voxel dosimetry in patients receiving radio-iodine ablation treatment of differentiated thyroid cancer (DTC). METHODS: Eighteen DTC patients were administered 1.11 GBq of 131I-NaI after near-total thyroidectomy and rhTSH stimulation. Two patients had two remnants, so in total dosimetry was performed for 20 sites. Three SPECT/CT scans were performed for each patient at 1, 2, and 3-7 days after administration. The activity, the remnant mass, and the maximum-voxel activity were determined from these images and from a recovery-coefficient curve derived from experimental phantom measurements. The cumulated activity was estimated using trapezoidal-exponential integration. Finally, the absorbed dose was calculated using S-values for unit-density spheres in whole-remnant dosimetry and S-values for voxels in maximum-voxel dosimetry. RESULTS: The mean absorbed dose obtained from whole-remnant dosimetry was 40 Gy (range 2-176 Gy) and from maximum-voxel dosimetry 34 Gy (range 2-145 Gy). For any given patient, the activity concentrations for each of the three time-points were approximately the same for the two methods. The effective half-lives varied (R = 0.865), mainly due to discrepancies in estimation of the longer effective half-lives. On average, absorbed doses obtained from whole-remnant dosimetry were 1.2 ± 0.2 (1 SD) higher than for maximum-voxel dosimetry, mainly due to differences in the S-values. The method-related differences were however small in comparison to the wide range of absorbed doses obtained in patients. CONCLUSIONS: Simple and consistent procedures for SPECT/CT based whole-volume and maximum-voxel dosimetry have been described, both based on experimentally determined recovery coefficients. Generally the results from the two approaches are consistent, although there is a small, systematic difference in the absorbed dose due to differences in the S-values, and some variability due to differences in the estimated effective half-lives, especially when the effective half-life is long. Irrespective of the method used, the patient absorbed doses obtained span over two orders of magnitude.

Study of cytogenetic toxicity of low-dose radioiodine therapy in hyperthyroid patients using a micronuclei assay.

OBJECTIVE: Radioiodine, in low doses, has been used as a treatment modality for hyperthyroidism worldwide for a long time. However, there is little information available on the severity of cytotoxicity of radioiodine at these low doses. The present investigation aimed to study the cytogenetic toxicity of low-dose radioiodine in hyperthyroid patients using a cytokinesis-blocked micronuclei (MN) assay. MATERIALS AND METHODOLOGY: All of the patients received radioiodine in the form of sodium iodine (oral form). Blood samples of these patients were collected before therapy and 3 months after therapy, and lymphocytes were analysed for MN assay. RESULTS: Peripheral blood lymphocytes were analysed in 74 hyperthyroid patients (52 men, 22 women). The results indicated a positive relationship between age and the frequency of MN. However, there was no statistically significant difference in MN frequency at 3 months after therapy in comparison with that before therapy. CONCLUSION: This study showed that the cytogenetic damage produced by low-dose radioiodine was transient and reversible. Thus, patients can be motivated to undergo this safe and easy procedure as a modality of treatment for hyperthyroidism.

Sodium/iodide symporter gene transfection increases radionuclide uptake in human cisplatin-resistant lung cancer cells

The sodium/iodide symporter (NIS) is involved in iodide uptake and has been used for the diagnosis and treatment of thyroid cancer. Transfection of the NIS gene in A549 human lung cancer cells can induce radioactive iodine (131I) and radioactive technetium (99mTc) uptake. The aim of the present study was to assess the role of NIS in 99mTc and 131I uptake by the A549/DDP human cisplatin-resistant lung cancer cell line. To do so, recombinant adenovirus, adenovirus-enhanced green fluorescent protein-human NIS (Ad-eGFP-hNIS) and Ad-eGFP-rat NIS (Ad-eGFP-rNIS) vectors were established. These vectors were transfected into A549/DDP cells and xenograft tumors in nude mice. Assessment of 99mTc and 131I uptake was performed. Results showed that the transfection efficiency of Ad-eGFP-hNIS and Ad-eGFP-rNIS in A549/DDP cells was at least 90 % in all experiments, and that the uptake ability of 99mTc and 131I was highly enhanced (14–18 folds for 99mTc, and 12–16 folds for 131I). However, the radionuclide concentration in transfected NIS genes’ A549/DDP cells reached a plateau within 30–60 min, indicating that NIS transport led rapidly to 99mTc and 131I saturation in cells. In xenograft tumor models, uptake of 99mTcO4 − was obviously higher in the hNIS and rNIS groups compared with controls. In conclusion, these results support the hypothesis that A549/DDP cells can effectively uptake 99mTc and 131I when transfected with the hNIS and rNIS gene. The rNIS or hNIS gene could be used as an effective method for the effective delivery of radioactive products to specific tissues for imagery and/or treatment (AU)

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Exposure levels associated with Na(131)I thyroid cancer patients: correlation with initial activity and clinical physical parameters.

Initial radiation exposure levels X (0) at 1 m from the navel of thyroid cancer patients were measured for 165 individuals at the time of ingestion. Some 61 patients had previously signed informed consent so only those patients could be assayed with regard to body parameters. While the activity was in the stomach, resultant X (0) values were seen to be linearly correlated with the total (131)I activity (A) given orally. Yet large differences in X (0) were seen; e.g., at A = 7.4 GBq, variations of a factor of four were found between the largest and smallest exposure rates. Correlation analyses were performed between normalized rate X (0)A-1 and several patient physical parameters. These included age, sex, height, weight, and BMI (body mass index). Only weight and BMI had significant linear correlation (p < 0.05) with normalized exposure rate. In the former case, the correlation coefficient ρ (weight) was -0.296 (p = 0.02). Using BMI as the independent variable, ρ (BMI) was -0.386 (p = 0.0021). With further analysis of the BMI variation, 95% confidence intervals could be determined at various BMI levels. For example, at 28 kg m(-2), the normalized rate varied between 0.039 and 0.0446 µGy h(-1) MBq(-1)-approximately a ±6.5% variation on the mean value of 0.0419 µGy h(-1) MBq(-1) at this BMI. Given such clinical information, differences in normalized exposure rate can be reduced to values on the order of ±10% or less for BMI values over the clinically relevant interval 20 to 40 kg m(-2).

A summary of the iodine supplementation study protocol (I2S2): a UK multicentre randomised controlled trial in preterm infants.

This paper summarises the study protocol for the randomised controlled trial of iodine supplementation in preterm infants. Iodine is essential for the synthesis of thyroxine, and thyroxine is essential for normal brain development in utero and for the first 2-3 years of life. The recommended iodine intake in parenteral nutrition regimens is 1 µg/kg/day and commercially available parenteral solutions for infants reflect these recommendations. In the absence of other iodine sources, infants are vulnerable to negative iodine balance and insufficiency. As many preterm infants are fed parenterally for prolonged periods with solutions which have been shown to be iodine-deficient, the I2S2 Trial was designed to establish whether iodine supplementation of preterm infants benefits neurodevelopment.

Experimental dry socket: microscopic and molecular evaluation of two treatment modalities / Alveolite experimental: análise microscópica e molecular de duas modalidades de tratamento

PURPOSE: To evaluate two treatment modalities of dry socket in rats and to discuss the first findings of the molecular analysis in this experimental model. METHODS: 84 rats underwent a tooth extraction were divided in 4 groups: I-uninfected socket (control), II-infected socket without any treatment, III-infected socket treated with irrigation of 2 percent sodium iodide and 3 percent hydrogen peroxide solution, IV-infected socket submitted to curettage, irrigation with physiological saline solution and fulfilled with metronidazole paste as base. The groups were subdivided in postoperative sacrifice periods: 6/15/28 days. A quantitative and a qualitative microscopic analysis was performed. Also, a quantitative analysis was performed using a RealTimePCR to evaluate the genes expression in the wound healing: Collagen Type I/COL-I, vascular endothelial growth factor/VEGF, osteocalcin/OCN, alkaline phosphatase/ALP, runt-related transcription factor 2/RUNX2 and tumor necrosis factor alpha/TNF-α. RESULTS: The group I showed higher bone formation, followed by groups IV, III, II respectively. The group II presented higher inflammatory infiltrate and the wound healing was delayed compared with other groups. It was obtained a significant positive correlation between bone neoformation and the expression of OCN and RUNX2, inflammatory infiltrate with TNF-α and a negative correlation between bone neoformation and TNF-α. CONCLUSION: No significant difference was found between the treatments.

OBJETIVO: Avaliar duas modalidades de tratamento da alveolite em ratos e discutir os primeiros achados de uma análise molecular neste modelo experimental. MÉTODOS: 84 ratos foram submetidos a uma extração dentária e foram divididos em quatro grupos: I- alvéolo não infectado (controle), II- alvéolo infectado sem tratamento, III- alvéolo infectado tratado com irrigação de iodeto de sódio a 2 por cento e solução de peróxido de hidrogênio a 3 por cento, IV- alvéolo infectado submetido à curetagem, irrigação com solução salina fisiológica e preenchimento com pasta a base de metronidazol. Os grupos foram subdivididos em períodos de sacrifício pós-operatório: 6/15/28 dias. Uma análise quantitativa e qualitativa microscópica foi realizada. Além disso, uma análise quantitativa foi realizada utilizando RealTimePCR para avaliar a expressão de genes no reparo alveolar: o colágeno tipo I / COL-I, o fator de crescimento endotelial vascular / VEGF, osteocalcina / OCN, fosfatase alcalina / ALP, fator de transcrição runt relacionados 2 / RUNX2 e fator de necrose tumoral alfa / TNF-α. RESULTADOS: O grupo I mostrou maior formação óssea, seguido pelos grupos IV, III, II, respectivamente. O grupo II apresentou maior infiltrado inflamatório e a cicatrização foi atrasada em comparação com outros grupos. Foi obtida uma correlação positiva entre a neoformação óssea e a expressão de OCN e RUNX2, infiltrado inflamatório com TNF-α e uma correlação negativa entre a neoformação óssea e TNF-α. CONCLUSÃO: Nenhuma diferença significativa foi encontrada entre os tratamentos.

Experimental dry socket: microscopic and molecular evaluation of two treatment modalities.

PURPOSE: To evaluate two treatment modalities of dry socket in rats and to discuss the first findings of the molecular analysis in this experimental model. METHODS: 84 rats underwent a tooth extraction were divided in 4 groups: I-uninfected socket (control), II-infected socket without any treatment, III-infected socket treated with irrigation of 2% sodium iodide and 3% hydrogen peroxide solution, IV-infected socket submitted to curettage, irrigation with physiological saline solution and fulfilled with metronidazole paste as base. The groups were subdivided in postoperative sacrifice periods: 6/15/28 days. A quantitative and a qualitative microscopic analysis was performed. Also, a quantitative analysis was performed using a RealTimePCR to evaluate the genes expression in the wound healing: Collagen Type I/COL-I, vascular endothelial growth factor/VEGF, osteocalcin/OCN, alkaline phosphatase/ALP, runt-related transcription factor 2/RUNX2 and tumor necrosis factor alpha/TNF-α. RESULTS: The group I showed higher bone formation, followed by groups IV, III, II respectively. The group II presented higher inflammatory infiltrate and the wound healing was delayed compared with other groups. It was obtained a significant positive correlation between bone neoformation and the expression of OCN and RUNX2, inflammatory infiltrate with TNF-α and a negative correlation between bone neoformation and TNF-α. CONCLUSION: No significant difference was found between the treatments.

Sodium iodide associated to salicylic acid in the topical management of chronic oral candidiasis: a randomized trial.

Candidiasis is a relevant problem in oral medicine practice. We compared the antimycotic activity of nystatin with a solution of sodium iodide associated to salicylic acid (SISA) in the topical management of chronic candidiasis. Consecutive patients affected by chronic candidiasis were randomly allocated to SISA (group A) or nystatin (group B). VAS and swab scores were recorded at the beginning and at the end of the study while the healing index was evaluated at the end of the study only. Data were analyzed by STATA 10 MP. Forty patients (20 male, 20 female) were randomized. SIAS was as effective as nystatin in affecting VAS (p greater than 0.05) and swab score (p greater than 0.05). A statistically significant reduction (p less than 0.05) of healing index was observed in both groups. No side effects were reported. SISA topical application, shows a comparable efficacy to the nystatin in the management of chronic oral candidiasis. Its use could represent an adequate alternative to the nystatin above all in the cases of drug-resistance. Further large scale randomized trials are warranted to confirm these preliminary findings.

Could the treatment of differentiated thyroid carcinoma with 3.7 and 5.55 GBq of (131I)NaI, on an outpatient basis, be safe?

OBJECTIVES: The first objective of this study was to evaluate the radiological impact on relatives and the environment because of outpatient treatment of differentiated thyroid carcinoma with 3.7 and 5.55 GBq of (131I)NaI. The second objective was to determine, analyze, and evaluate whole-body radiation dose to caregivers, the production of contaminated solid waste, and the potentiality of radiation dose and surface contamination existing inside patients' households. METHODS: Twenty patients were treated on an outpatient basis, taking into consideration their acceptable living conditions, interests, and willingness to comply with medical and radiation-safety guidelines. The caregivers themselves, as well as the potentiality of the radiation dose inside patients' residences, were monitored with a thermo-luminescence dosimeter. Surface contamination and contaminated solid wastes were identified and measured by using a Geiger-Müller detector. RESULTS AND DISCUSSION: Twenty-six monitored individuals received accumulated effective radiation doses of less than 1.0 mSv, and only one 2.8 mSv, throughout the 7 days of measurement. The maximum registered value for the potential of radiation dose inside all living areas was 1.30 mSv. The monitored surface contamination inside patients' dwellings showed a mean value of 4.2 Bq/cm for all surfaces found to be contaminated. A total of 2.5 l of contaminated solid waste was generated by the patients with 3.33 MBq of all estimated activity. CONCLUSION: This study revealed that the treatment of differentiated thyroid carcinoma with 3.7 and 5.55 GBq of (131I)NaI, on an outpatient basis, can be safe when overseen by qualified professionals and with an adapted radiation-protection guideline. Even considering the radioiodine activity level and the dosimetric methodology applied here, negligible human exposure and a nonmeasurable radiological impact to the human environment were found.

Mudanças evolutivas no tratamento da doença de Graves com iodo radioativo: 12 anos de experiência em um hospital universitário / Changing trends in the treatment of Graves' disease with radioiodine: a 12-year experience in a university hospital

OBJETIVO: Avaliar a mudança no perfil e abordagem dos pacientes com doença de Graves submetidos a dose terapêutica de radioiodo. MATERIAIS E MÉTODOS: Avaliamos, retrospectivamente, 226 pacientesportadores de doença de Graves submetidos a dose terapêutica de radioiodo entre janeiro de 1990 e dezembro de 2001. O período de 12 anos foi dividido em três períodos de 4 anos para fins de análise estatística,sendo comparadas variáveis clínicas e laboratoriais nos períodos descritos. RESULTADOS: Constatamos que o número de pacientes encaminhados para a dose terapêutica, assim como o percentual de pacientes do sexo feminino (de 62% para 86%; p = 0,005), tiveram incremento significativo. Houve aumento significativo no percentual de pacientes em uso de metimazol previamente à dose terapêutica (de 9,1% para 35,6%;p = 0,03). A dose média de iodo administrada também teve incremento significativo (de 7,6 mCi para 12,7mCi; p = 0,000003), com reflexo direto em um maior percentual de pacientes curados (de 55,6% para 83,7%; p = 0,004) um ano pós-dose terapêutica. CONCLUSÃO: A dose terapêutica de radioiodo tem sido um método cada vez mais aceito nos pacientes com doença de Graves e a dose administrada tem sido cada vez maior, no intuito de cura permanente e diminuição das chances de recidiva.

OBJECTIVE: To evaluate the changes in clinical parameters and in the approach to patients submitted to radioiodine therapy for Graves' disease. MATERIALS AND METHODS: Dossiers of 226 patients submitted to radioiodine therapy for Graves' disease in the period between January 1990 and December 2001 were retrospectively evaluated. For the purposes of statistical analysis, the 12-year period was subdivided into three periods of 4 years, with a comparison of clinical and laboratory variables in these periods. RESULTS: The authors have observed that the total number of patients referred for radioiodine therapy as well as the percentage of female patients presented a significant increase (from 62% to 86%; p = 0.005). The percentage of patients pretreated with methimazole before radioiodine therapy increased significantly (from 9.1% to35.6%; p = 0.03). The mean radioiodine dose delivered has also presented a significant increase (from 7.6 mCi to 12.7 mCi; p = 0.000003) with a direct reflection on a higher percentage of patients cured one year after the radioiodine therapy (from 55.6% to 83.7%; p = 0.004). CONCLUSION: Radioiodine therapy has increasingly been accepted for treatment of patients with Graves' disease and the doses delivered have increased to achieve a permanent cure as well as a reduction of the chances of recurrence.