99mTc-HYNIC/Cy7-Fab(Bevacizumab): su empleo como agente de imagen en mieloma múltiple / 99mTc-HYNIC/Cy7-Fab(Bevacizumab): its use as an imaging agent in Multiple Myeloma / 99mTc-HYNIC/Cy7-Fab (Bevacizumab): seu uso como agente de imagem em mieloma múltiplo

Introducción: el mieloma múltiple es un trastorno hematológico maligno y el segundo cáncer de la sangre más frecuente. El proceso de la angiogénesis tumoral es fundamental para el crecimiento y metástasis de muchos tipos de tumores, incluido en mieloma múltiple. Se sabe que la sobreexpresión del factor de crecimiento endothelial vascular se encuentra asociado a un mal pronóstico en esta patología, representando un blanco clave para la terapia anti-angiogénica en mieloma múltiple. El anticuerpo monoclonal Bevacizumab es capaz de unirse con gran afinidad al factor de crecimiento endothelial vascular bloqueando su acción. Objetivo: evaluar el Fab(Bevacizumab) marcado con 99mTc o Cy7 como potenciales agentes de imagen moleculares de la expresión de factor de crecimiento endothelial vascular en mieloma múltiple. Material y métodos: la expresión de factor de crecimiento endothelial vascular fue analizada mediante citometría de flujo en la línea celular huaman de mieloma múltiple, la MM1S. Fab(Bevacizumab) fue producido mediante digestión de Bevacizumab con papaína, conjugado a NHS-HYNIC-Tfa y radiomarcado con 99mTc. Se realizaron estudios de biodistribución y de tomografía computarizada por emisión del fotón simple. A su vez, Fab(Bevacizumab) fue marcado con Cy7 para obtener imágenes de fluorescencia in vivo hasta 96 horas. Resultados: el análisis por citometría de flujo en la línea celular MM1S reveló que la expresión de factor de crecimiento endothelial vascular es predominantemente intracelular. Los estudios de biodistribución y SPECT/CT del complejo 99mTc-HYNIC-Fab(Bevacizumab) mostraron una rápida eliminación sanguínea y una significativa captación a nivel renal y tumoral. Las imágenes por fluorescencia empleando Cy7-Fab(Bevacizumab) permitieron la visualización tumoral hasta 96 h p.i. Conclusiones: logramos visualizar la expresión de factor de crecimiento endothelial vascular in vivo en mieloma múltiple mediante el empleo del fragmento Fab del anticuerpo anti-VEGF (Bevacizumab) marcado con 99mTc y Cy7. Estos nuevos agentes de imagen molecular podrían ser empleados potencialmente en el ámbito clínico para la estadificación y el seguimiento de pacientes con mieloma múltiple, mediante la visualización radioactiva in vivo de la expresión de factor de crecimiento endothelial vascular en todo el cuerpo. La imagen óptica de estos trazadores mejoraría el muestreo tumoral y podría guiar la extirpación quirúrgica.

Introduction: Multiple myeloma is a hematologic malignancy and the second most common blood cancer. The process of tumor angiogenesis is central to the growth and metastasis of many types of tumors, including multiple myeloma. Overexpression of vascular endothelial growth factor is known to be associated with poor prognosis in this pathology, representing a key target for anti-angiogenic therapy in multiple myeloma. The monoclonal antibody Bevacizumab is able to bind with high affinity to vascular endothelial growth factor blocking its action. Objective: to evaluate 99mTc- or Cy7-labeled Fab(Bevacizumab) as potential molecular imaging agents of vascular endothelial growth factor expression in multiple myeloma. Methods: Vascular endothelial growth factor expression was analyzed by flow cytometry in the multiple myeloma huaman cell line, MM1S. Fab(Bevacizumab) was produced by digestion of Bevacizumab with papain, conjugated to NHS-HYNIC-Tfa and radiolabeled with 99mTc. Biodistribution and single photon emission computed tomography studies were performed. In turn, Fab(Bevacizumab) was labeled with Cy7 to obtain in vivo fluorescence images up to 96 hours. Results: Flow cytometry analysis in the MM1S cell line revealed that vascular endothelial growth factor expression is predominantly intracellular. Biodistribution and SPECT/CT studies of the 99mTc-HYNIC-Fab(Bevacizumab) complex showed rapid blood clearance and significant renal and tumor uptake. Fluorescence imaging using Cy7-Fab(Bevacizumab) allowed tumor visualization up to 96 h p.i. Conclusions: we were able to visualize vascular endothelial growth factor expression in vivo in multiple myeloma using the Fab fragment of the anti-VEGF antibody (Bevacizumab) labeled with 99mTc and Cy7. These new molecular imaging agents could potentially be employed in the clinical setting for staging and monitoring of patients with multiple myeloma by in vivo radioactive visualization of vascular endothelial growth factor expression throughout the body. Optical imaging of these tracers would improve tumor sampling and could guide surgical excision.

Introdução: O mieloma múltiplo é uma malignidade hematológica e o segundo câncer de sangue mais comum. O processo de angiogênese tumoral é fundamental para o crescimento e a metástase de muitos tipos de tumores, incluindo o mieloma múltiplo. Sabe-se que a superexpressão do fator de crescimento endotelial vascular está associada a um prognóstico ruim no mieloma múltiplo, representando um alvo importante para a terapia antiangiogênica no mieloma múltiplo. O anticorpo monoclonal Bevacizumab é capaz de se ligar com alta afinidade ao fator de crescimento endotelial vascular e bloquear sua ação. Objetivo: avaliar o Fab(Bevacizumab) marcado com 99mTc ou Cy7 como possíveis agentes de imagem molecular da expressão do fator de crescimento endotelial vascular no mieloma múltiplo. Métodos: A expressão do fator de crescimento endotelial vascular foi analisada por citometria de fluxo na linha celular de mieloma múltiplo MM1S. O Fab(Bevacizumab) foi produzido pela digestão do Bevacizumab com papaína, conjugado com NHS-HYNIC-Tfa e radiomarcado com 99mTc. Foram realizados estudos de biodistribuição e tomografia computadorizada por emissão de fóton único. Por sua vez, o Fab(Bevacizumab) foi marcado com Cy7 para geração de imagens de fluorescência in vivo por até 96 horas. Resultados: A análise de citometria de fluxo na linha celular MM1S revelou que a expressão do fator de crescimento endotelial vascular é predominantemente intracelular. Os estudos de biodistribuição e SPECT/CT do complexo 99mTc-HYNIC-Fab(Bevacizumab) mostraram uma rápida depuração sanguínea e uma captação renal e tumoral significativa. A imagem de fluorescência usando Cy7-Fab(Bevacizumab) permitiu a visualização do tumor até 96 horas p.i. Conclusões: Conseguimos visualizar a expressão do fator de crescimento endotelial vascular in vivo no mieloma múltiplo usando o fragmento Fab do anticorpo anti-VEGF (Bevacizumab) marcado com 99mTc e Cy7. Esses novos agentes de imagem molecular poderiam ser usados no cenário clínico para o estadiamento e o monitoramento de pacientes com mieloma múltiplo, visualizando radioativamente a expressão do fator de crescimento endotelial vascular in vivo em todo o corpo. A geração de imagens ópticas desses traçadores melhoraria a amostragem do tumor e poderia orientar a excisão cirúrgica.

A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis / 中华医学杂志(英文版)

BACKGROUND@#Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA.@*METHODS@#Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48.@*RESULTS@#At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed.@*CONCLUSIONS@#This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.

Radiolabeling of cidofovir with technetium-99m and biodistribution studies

Radiolabeling cidofovir with technetium-99m (99mTc-CDV) is an innovative procedure that enables real-time monitoring of the drug. Essays were performed in vitro, showing high radiolabel stability within 24 h. Blood clearance, biodistribution studies, and scintigraphic images were performed in healthy mice in order to evaluate the profile of the drug in vivo. 99mTc-CDV showed biphasic blood circulation time and significant kidney uptake, indicating that 99mTc-CDV is preferentially eliminated by the renal route. Bones also showed important uptake throughout the experiment. In summary, cidofovir was successfully labeled with technetium-99m and might be used in further studies to track the drug.

Utilização de radiofármacos marcados com tecnécio 99m como potenciais marcadores na obtenção de imagens de perfusão miocárdica / Using technetium-99m-marked radiopharmaceuticals as potential markers in obtaining myocardial perfusion images

A Organização Mundial de Saúde (OMS) aponta as doenças cardiovasculares como a principal causa de morte no mundo, caracterizando um grave problema na saúde pública. Os três tipos de doenças que mais acarretam em óbito são: acidente vascular cerebral, seguido de infarto agudo do miocárdio e outras doenças isquêmicas do coração.Apesar dos avanços terapêuticos das últimas décadas, o infarto ainda apresenta altas taxas de mortalidade. Para as pessoas com doenças cardiovasculares ou com alto risco cardiovascular é fundamental o diagnóstico precoce da doença. A cintilografia de perfusão miocárdica é um método de investigação diagnóstica e prognóstico não invasivo de várias doenças cardiovasculares. Esse exame consiste na administração de um radiofármaco para obtenção de imagens de perfusão cardíaca. Dois traçadores marcados com Tecnécio-99m são amplamente utilizados na clínica, porém, esses dois radiofármacos não atendem aos requisitos de um agente de perfusão ideal, por sofrerem significativa excreção biliar, produzindo artefatos na imagem, o que pode inteferir um diagnóstico preciso, já que a qualidade é comprometida, e prolongando o tempo de obtenção da imagem após a administração do radiotraçador. Para superar essa lacuna, pesquisadores vêm estudando novos complexos catiônicos marcados com o Tecnécio. O objetivo desse artigo é fazer uma revisão, abordando a literatura sobre os radiofármacos que estão sendo estudados, suas vantagens e desvantagens sobre os traçadores já utilizados, e sobre sua potencial utilização na obtenção de imagem de perfusão cardíaca.

The World Health Organization (WHO) acknowledges cardiovascular diseases as the leading cause of death in the world, being regarded as a serious public health issue. The three types of diseases with the greatest mortality are: stroke, followed by acute myocardial infarction (AMI) and other ischemic heart diseases. Despite the therapeutic advances of the last decades, AMI still presents high mortality rates. Early diagnosis is essential for people with cardiovascular diseases or with a high cardiovascular risk. Myocardial perfusion scintigraphy is a method of diagnostic investigation and noninvasive prognosis of various cardiovascular diseases. This examination consists in the administration of a radiopharmaceutical drug to obtain images of cardiac perfusion. Two tracers labeled with Technetium-99m are widely used, however, these two radiopharmaceuticals do not meet the requirements of an ideal perfusion agent, because they have a high liver absorption, producing artifacts in the image, which can disrupt a precise diagnosis, since the quality is compromised, and prolonging the imaging time after administration of the radioisotope. To overcome this gap, researchers have been studying new cationic complexes marked with technetium. The objective of this article is to review the literature on the radiopharmaceuticals being studied, their advantages and disadvantages on the tracers already used, and their potential use in obtaining a cardiac perfusion image.

Clinical usefulness of intraoperative parathyroid hormone monitoring for primary hyperparathyroidism

PURPOSE: The availability of intraoperative parathyroid hormone (IOPTH) monitoring allows successful focused parathyroidectomy for primary hyperparathyroidism (pHPT). The objective of this study was to report our initial experience in IOPTH monitoring during parathyroid surgery for primary hyperparathyroidsim. METHODS: Between May 2011 and February 2013, 37 patients underwent focused parathyroidectomy due to pHPT. IOPTH monitoring based on Miami criteria was used to confirm complete excision of hyperfunctioning parathyroid gland during surgery. Medical records of patients were reviewed retrospectively. RESULTS: Preoperative mean maximal calcium level was 11.7 ± 0.9 mg/dL. Preoperative technetium (99mTc) sestamibi scan and ultrasonography identified 32 of 37 (86.5%) and 29 of 37 (78.4%) of abnormal parathyroid glands, retrospectively. Results of the 2 imaging modalities were discordant for 8 cases (21.6%). The mean pre-excision PTH level was 147.2 ± 201.5 pg/mL. At 5- and 10-minute post tumor resection, PTH levels were 65.3 ± 25.4 pg/mL and 47.5 ± 24.3 pg/mL, respectively. In all cases, IOPTH levels fell by at least 50% after removing all suspected abnormal glands. All patients had a successful return to normocalcemia after surgery (mean follow-up period: 60.2 ± 15.4 months). CONCLUSION: Surgeon could confirm complete excision of abnormal hyperfunctioning parathyroid glands by IOPTH monitoring during surgery for pHPT. IOPTH monitoring can maximize performance of successful focused para thyroidectomy for pHPT, especially when preoperative imaging results are discordant.

In vivo imaging of breast tumors by a 99mTc radiolabeled probe targeting microRNA-155 in mice models / 北京大学学报(医学版)

OBJECTIVE@#MicroRNA-155 (miR-155) is significantly highly expressed in breast cancer, lung cancer, liver cancer and other malignant tumors. This study was to design and construct a radiolabeled probe targeting miR-155 for in vivo imaging in breast cancer.@*METHODS@#Anti-miR-155 oligonucleotide (AMO-155) was chemically synthesized with 2' OMe modification. Its 5' end was linked with acetyl amine group. After chelated with a bifunctional chelator NHS-MAG3, AMO-155 was radiolabeled with 99mTc using stannous chloride. The serum stability was evaluated at cellular level. In vivo imaging was performed in MCF-7 tumor bearing mice after the administration of 99mTc radiolabeled AMO-155 and scramble control probes, respectively. Furthermore, the blocked imaging of tumor bearing mice was obtained after the injection of unlabeled AMO-155 2 hours ahead. MCF-7 and MDA-MB-231 tumor bearing mice with different expression level of miR-155 were imaged, respectively. Quantitative real-time PCR (qRT-PCR) was used to identify the expression level of miR-155 in the bearing tumors.@*RESULTS@#99mTc-AMO-155 was prepared with high radiolabeled efficiency (97%), radiochemical purity (greater than 98%), and radioactive specific activity (3.75 GBq/μg). 99mTc-AMO-155 was stable in fresh human serum for 12 hours. After the administration via tail vein, 99mTc-AMO-155 displayed significant accumulation in MCF-7 bearing tumors with high expression level of miR-155, whereas 99mTc-control showed little accumulation. After blocked with unlabeled AMO-155, the tumor could not be visualized clearly after the administration of 99mTc-AMO-155. Furthermore, 99mTc-AMO-155 could show the differential expression of miR-155 in vivo. MCF-7 tumor was shown with significantly higher radioactive accumulation than MDA-MB-231, based on its higher expression level of miR-155, which was verified by qRT-PCR.@*CONCLUSION@#99mTc-labeled AMO-155 with chemical modification showed good serum stability and in vivo tumor targeting ability. This study provides a potential probe for in vivo imaging of breast cancer.

Identification of the sentinel lymph node using hemosiderin in locally advanced breast cancer / Identificação do linfonodo sentinela utilizando hemossiderina em casos de câncer de mama localmente avançado

ABSTRACT Objective: to verify the agreement rate in the identification of sentinel lymph node using an autologous marker rich in hemosiderin and 99 Technetium (Tc99) in patients with locally advanced breast cancer. Methods: clinical trial phase 1, prospective, non-randomized, of 18 patients with breast cancer and clinically negative axilla stages T2=4cm, T3 and T4. Patients were submitted to sub-areolar injection of hemosiderin 48 hours prior to sentinel biopsy surgery, and the identification rate was compared at intraoperative period to the gold standard marker Tc99. Agreement between methods was determined by Kappa index. Results: identification rate of sentinel lymph node was 88.9%, with a medium of two sentinel lymph nodes per patients. The study identified sentinel lymph nodes stained by hemosiderin in 83.3% patients (n=15), and, compared to Tc99 identification, the agreement rate was 94.4%. Conclusion: autologous marker rich in hemosiderin was effective to identify sentinel lymph nodes in locally advanced breast cancer patients.

RESUMO Objetivo: verificar a taxa de concordância na identificação do linfonodo sentinela utilizando um marcador autólogo rico em hemossiderina e o Tecnécio 99 (Tc99) em casos de câncer de mama localmente avançados. Métodos: ensaio clínico fase 1, do tipo prospectivo, não randomizado, em 18 pacientes portadoras de câncer de mama com axila clinicamente negativa em estádio T2=4cm, T3 e T4. As pacientes foram submetidas à injeção subareolar de um marcador autólogo rico em hemossiderina 48 horas antes do procedimento cirúrgico para biópsia do linfonodo sentinela, e sua taxa de identificação foi comparada, no intraoperatório, com o marcador radioativo Tc99 (padrão-ouro). A concordância entre os métodos foi estabelecida pelo índice de Kappa. Resultados: a taxa de identificação do linfonodo sentinela foi de 88,9%, com uma média de dois linfonodos sentinelas por paciente. O estudo identificou os linfonodos sentinelas corados com hemossiderina em 83,3% dos casos (n=15), quando comparados com a taxa de identificação do Tc99, tendo sido observada concordância em 94,4% dos casos estudados. Conclusão: o marcador autólogo rico em hemossiderina se mostrou eficaz na identificação do linfonodo sentinela em casos de câncer de mama localmente avançado.

Predictores clínicos y de imagen funcional con 99tecnecio - sestamibi para diferenciar el grado de malignidad en gliomas cerebrales / Clinical and functional image with 99tecnecio - sestamibi predictors to differentiate the grade of malignancy of brain gliomas

RESUMEN INTRODUCCIÓN: Los gliomas son los tumores primarios más frecuentes del Sistema Nervioso Central. La tomografia de Emisión de Fotón Único (SPECT) es una técnica de imagen funcional que nos permite acceder a información molecular y diferenciar los gliomas entre sí y de otras entidades nosológicas.. De ello depende la estrategia terapéutica a emplear y el pronóstico en estos pacientes. OBJETIVO: determinar la utilidad de las características clínicas de los pacientes al ingreso y de la SPECT cerebral con 99Tc-MIBI para diferenciar el grado de malignidad de los gliomas cerebrales. PACIENTES Y MÉTODOS: estudio observacional, descriptivo y prospectivo realizado en pacientes del Hospital Clínico Quirúrgico "Hermanos Ameijeiras" y del Hospital Universitario "General Calixto García" durante el período mayo 2012 - febrero 2015. La muestra quedó constituida por 102 pacientes con diagnóstico confirmado de glioma cerebral y con estudio de SPECT Cerebral con 99mTc-MIBI. RESULTADOS: Los principales síntomas y signos, así como el índice de Karnofsky al ingreso no mostraron diferencias significativas respecto al grado de malignidad de los gliomas cerebrales estudiados. Los pacientes con gliomas de alto grado se caracterizaron por una elevación de todos los índices tumorales, así como de la cuantificación de la actividad, concentración volumétrica del 99mTc-MIBI para ambas fases, aunque más marcado para la fase tardía e índice de retención. El Indice tumor corteza contralateral en fase tardía mostró una sensibilidad, especificidad, valor predictivo positivo y negativo de 98,9%, 94,0%, 63,0% y 99,0% respectivamente para diferenciar el grado de malignidad de los gliomas cerebrales. La razón fase tardía/fase temprana del índice tumor/corteza contralateral mostró valores de sensibilidad de 94,1%, especificidad de 98,5%, valor predictivo positivo de 98,7% y valor predictivo negativo de 98,8%. El índice de retención del radiofármaco tuvo una sen-sibidad de 99%, especificidad de 89%, y valores predictivos positivo y negativo de 95% y 99% respectivamente. CONCLUSIÓN: La combinación de: Indice tumor corteza contralateral en fase tardía, razón fase tardía/fase temprana del ÍNDICE tumor/corteza contralateral y el índice de retención del radiofármaco son los parámetros más útiles para predecir el grado de malignidad de los gliomas cerebrales utilizando la SPECT con 99mTc-MIBI.

SUMMARY INTRODUCTION: Gliomas are the most common primary tumors of the Central Nervous System. Single Photon Emission Tomography (SPECT) is a functional imaging technique that allows us to access molecular information and differentiate gliomas from each other and from other entities. It depends on the therapeutic strategy to be used and the prognosis in these patients. OBJECTIVE: To determine the utility of the clinical characteristics of patients on admission and of the brain SPECT with 99mTc-MIBI to differentiate the degree of malignancy of brain gliomas. Patients and methods: An observational, descriptive and prospective study carried out in patients from "Hermanos Ameijeiras" Hospital and "Calixto García" University Hospital during the period May 2012 to February 2015. The sample consisted of 102 patients with confirmed diagnosis of brain glioma and with study of Brain SPECT with 99mTc-MIBI. RESULTS: The main symptoms and signs, as well as the Karnofsky index on admission did not show significant differences regarding the degree of malignancy of the brain gliomas studied. Patients with high-grade gliomas were characterized by an elevation of all tumor indices as well as quantification of activity, volumetric concentration of 99mTc-MIBI for both phases, although more marked for the late phase and retention index. Tumor / contralateral cortex index in late phase showed a sensitivity, specificity, positive and negative predictive value of 98.9%, 94.0%, 63.0%, and 99.0% respectively to differentiate the degree of malignancy of brain gliomas. Late phase / early phase ratio of the tumor / contralateral cortex index showed sensitivity values of 94.1%, specificity of 98.5%, positive predictive value of 98.7%, and negative predictive value of 98.8%. Radiopharmaceutical retention index had a sensitivity of 99%, specificity of 89%, and positive and negative predictive values of 95% and 99% respectively. CONCLUSION: The combination of: Tumor / contralateral cortex index in late phase, late phase / early phase ratio of the tumor / contralateral cortex index, and radiopharmaceutical retention index are the most useful parameters for predicting the degree of malignancy of brain gliomas using SPECT with 99mTc-MIBI.

Radionuclide Esophageal Transit Scintigraphy in Primary Hypothyroidism

BACKGROUND/AIMS: Esophageal dysmotility is associated with gastrointestinal dysmotility in various systemic and neuroregulatory disorders. Hypothyroidism has been reported to be associated with impaired motor function in esophagus due to accumulation of glycosaminoglycan hyaluronic acid in its soft tissues, leading to changes in various contraction and relaxation parameters of esophagus, particularly in the lower esophageal sphincter. In this study we evaluated esophageal transit times in patients of primary hypothyroidism using the technique of radionuclide esophageal transit scintigraphy. METHODS: Thirty-one patients of primary hypothyroidism and 15 euthyroid healthy controls were evaluated for esophageal transit time using 15–20 MBq of Technetium-99m sulfur colloid diluted in 10–15 mL of drinking water. Time activity curve was generated for each study and esophageal transit time was calculated as time taken for clearance of 90% radioactive bolus from the region of interest encompassing the esophagus. Esophageal transit time of more than 10 seconds was considered as prolonged. RESULTS: Patients of primary hypothyroidism had a significantly increased mean esophageal transit time of 19.35 ± 20.02 seconds in comparison to the mean time of 8.25 ± 1.71 seconds in healthy controls (P < 0.05). Esophageal transit time improved and in some patients even normalized after treatment with thyroxine. A positive correlation (r = 0.39, P < 0.05) albeit weak existed between the serum thyroid stimulating hormone and the observed esophageal transit time. CONCLUSIONS: A significant number of patients with primary hypothyroidism may have subclinical esophageal dysmotility with prolonged esophageal transit time which can be reversible by thyroxine treatment. Prolonged esophageal transit time in primary hypothyroidism may correlate with serum thyroid stimulating hormone levels.

Pelvic Insufficiency Fracture in Severe Osteoporosis Patient / 대한고관절학회지

PURPOSE: To evaluate clinical features and the effect of parathyroid hormone (PTH) on treatment outcomes of patients with pelvic insufficiency fractures. MATERIALS AND METHODS: Fifteen patients diagnosed with pelvic insufficiency fractures were evaluated retrospectively. All patients had osteoporosis with mean lumbar T score of −3.9 (range, −3.1 to −6.4) and the mean age was 76.5 years. In all cases, simple radiography and computed tomography was used for final diagnosis; additional magnetic resonance imaging and technetium bone scans were used to confirm the diagnosis in 2 and 6 patients, respectively. Initial conservative treatment was used in all cases; treatment with PTH was applied in 5 cases. Radiological follow-up was done every 4 weeks up to 6 months and every 3 months thereafter. Symptom improvement was measured using visual analogue scale (VAS) score. RESULTS: Fractures were located: i) sacrum and pubis (9 cases), ii) isolated sacrum (4 cases) and iii) isolated pubis (2 cases). One case showed fracture displacement and pain aggravation at 4 week follow-up which was treated with percutaneous sacro-iliac fixation using cannulated screws. Duration of bone union was significantly shorter in the patients who used PTH (P<0.05). VAS scores were also lower in the group treated with PTH; however, statistical significance was not reached. CONCLUSION: In patients with osteoporosis, a pelvic insufficiency fracture should be considered if pain is experienced in the pelvic area in the absence of major trauma. While nonoperatic has been shown to be sufficient for treatment, our study shows that PTH therapy shortens treatment period and could be a favorable treatment option.

Comparação da hemossiderina com o tecnécio-99 na identificação do linfonodo sentinela do câncer de mama. /Paulo Henrique Diógenes Vasques

INTRODUÇÃO E OBJETIVO: Atualmente, a Biopsia do Linfonodo Sentinela (BLS) substitui oesvaziamento axilar no estadiamento do câncer de mama inicial com axila clinicamentenegativa. O tecnécio 99 (Tc99) é o padrão ouro para identificação do Linfonodo Sentinela(LS) da mama. Os corantes azuis são uma opção menos onerosa e mais difundida no Brasil.Estes corantes são responsáveis pelas reações adversas e de hipersensibilidade que, emborararas, podem pôr em risco à vida dos pacientes. Há interesse na descoberta de novassubstâncias equivalentes e com menores efeitos colaterais às usadas na BLS. Aqui se avaliama segurança e a equivalência do uso da hemossiderina, em comparação ao tecnécio 99 (Tc99)na BLS no câncer de mama. A hemossiderina é um derivado da hemoglobina, identificada emestudo pré-clínico, que se mostrou eficaz na BLS da mama da cadela. O objetivo destapesquisa é avaliar a segurança e a potencial equivalência do uso da hemossiderina emcomparação com o Tc99 na BLS da mama humana...

INTRODUCTION AND OBJECTIVE: Sentinel Lymph Node Biopsy (SLNB) has currently replaced axillary dissection in early - stage breast cancer in clinically tumor - free patients. Technetium - 99 ( 99 Tc) is the gold standard for the identification of Breast Sentinel Ly mph Node (SLN). Blue dyes are a less expensive and widely used option in Brazil. These dyes are responsible for several adverse and hypersensitivity reactions that – although rare – ’ v at risk. There is an interest in the discovery of new equivalent substances with less side effects than those used in SLNB. This research assesses the safety and equivalence of the use of hemosiderin in SLNB in breast cancer compared to technetium - 99 ( 99 Tc). Hemosiderin is a hemoglobin derivate identifie d in a preclinical trial that has proven to be effective in the SLNB f f ’. Th f h h h f y equivalence of the use of hemosiderin in SLNB in human breast compared to the 99 Tc...

Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m

Background Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with 99mTc. Methods Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with 99mTc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2. 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values < 0.05). Results Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 μmol.L−1 (S. aureus) and 10.10 μmol.L−1 (E. coli). Thus, only the latter was radiolabeled with 99mTc. The radiochemical purity analysis of LyeTx I-K-HYNIC-99mTc showed that the optimal radiolabeling conditions (10 μg of LyeTx I-K-HYNIC; 250 μg of SnCl2. 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n= 3). However, RP-HPLC data suggested 99mTc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). Conclusions The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.(AU)

Sentinel node biopsy using blue dye and technetium99 in advanced gastric cancer: anatomical drainage and clinical application

Lymph node metastases are an independent prognosis factor in gastric carcinoma (GC) patients. Radical lymphadenectomy can improve survival but it can also increase surgical morbidity. As a principle, sentinel node (SN) navigation surgery can avoid unnecessary lymphadenectomy without compromising prognosis. In this pilot study, 24 patients with untreated GC were initially screened for SN navigation surgery, of which 12 were eligible. Five patients had T2 tumors, 5 had T3 tumors and 2 had T1 tumors. In 33% of cases, tumor diameter was greater than 5.0 cm. Three hundred and eighty-seven lymph nodes were excised with a median of 32.3 per patient. The SN navigation surgery was feasible in all patients, with a median of 4.5 SNs per patient. The detection success rate was 100%. All the SNs were located in N1 and N2 nodal level. In 70.9% of cases, the SNs were located at lymphatic chains 6 and 7. The SN sensitivity for nodal staging was 91.6%, with 8.3% of false negative. In 4 patients who were initially staged as N0, the SNs were submitted to multisection analyses and immunohistochemistry, confirming the N0 stage, without micrometastases. In one case initially staged as negative for nodal metastases based on SN analyses, metastases in lymph nodes other than SN were found, resulting in a 20% skip metastases incidence. This surgery is a reproducible procedure with 100% detection rate of SN. Tumor size, GC location and obesity were factors that imposed some limitations regarding SN identification. Results from nodal multisection histology and immunohistochemistry analysis did not change initial nodal staging.

Bone Scintigraphy in the Diagnosis of Rheumatoid Arthritis: Is There Additional Value of Bone Scintigraphy with Blood Pool Phase over Conventional Bone Scintigraphy?

We aimed to investigate the value of bone scintigraphy with additional blood pool phase (BSBP), compared with conventional bone scintigraphy (CBS), in the assessment of rheumatoid arthritis (RA). A total of 242 patients (43 males, 199 females; 14-78 years) with arthralgia, and underwent BSBP were retrospectively analyzed. On the first physical examination, active arthritis was found in 128 of the 242 patients. Clinical diagnosis was made by a rheumatologist on the basis of the 1987 American College of Rheumatology (ACR) criteria, which are considered to be the gold standard. The diagnostic performances and prognostic value of BSBP and CBS were analyzed in the total patients with arthralgia and in the patients with arthritis. The sensitivity of BSBP (84.2%, 80/95) were significantly higher than that of CBS (74.8%, 72/95) in the patients with arthralgia (P = 0.039). When BSBP was interpreted with the results of elevated/positive anti-CCP antibody, its accuracy over CBS also became significantly higher (86.0%, 208/242 vs. 83.1%, 201/242 respectively, P = 0.021). The diagnostic odds ratio of BSBP positivity was higher than CBS positivity in the patients with arthralgia (26.0, 12.9-52.4 vs. 21.1, 10.8-41.3) and with arthritis (12.0, 4.9-29.4 vs. 10.0, 4.2-23.4). Both BSBP and CBS appear to provide acceptable accuracy and comparable diagnostic performance for diagnosis of RA. However, in the patients with arthralgia, BSBP was found to be more sensitive than CBS and more accurate when interpreted with the result of anti-CCP antibody. This could help physicians diagnose RA in daily clinical practice.

Comparison between hemosiderin and Technetium-99 in sentinel lymph node biopsy in human breast cancer

PURPOSE: To assess the safety and potential equivalence of the use of hemosiderin compared to the Technetium-99 in sentinel lymph node biopsy in human breast cancer. METHODS: Non-random sample of 14 volunteer women diagnosed with breast cancer with primary tumors (T1/T2) and clinically tumor-free axilla were submitted to the identification of sentinel lymph node using hemosiderin obtained from autologous blood injected in the periareolar region 24h before surgery on an outpatient basis. Patients received preoperative subareolar intradermal injection of Technetium-99 in the immediate preoperative period. Patients were submitted to sentinel lymph node biopsy, with incision in the axillary fold guided by Gamma-Probe, dissection by planes until the identification of the point of maximum uptake of Technetium-99, identifying the marked nodes and their colors. All surgical specimens were sent for pathological and immunohistochemical study. RESULTS: The results showed no evidence of side effects and/or allergic and non-allergic reactions in patients submitted to SLNB with hemosiderin. The SLN identification rate per patient was 100%. SLNB identification rate per patient with hemosiderin was the same as that of Technetium, with a concordance rate of 100% between the methods. CONCLUSION: Hemosiderin is a safe dye that is equivalent to Technetium in breast sentinel lymph node biopsy.

Imaging features of an intraosseous arteriovenous malformation in the tibia

Primary intraosseous arteriovenous malformations (AVMs) are rare and have only been occasionally reported. We herein report a histologically proven case of primary intraosseous AVM in the tibia, which mimicked a fibrous tumour on radiography. This presentation carries a risk of triggering acute large haemorrhage through unnecessary biopsy. In intraosseous AVM, the magnetic resonance (MR) imaging features typical of a soft tissue AVM are absent, making diagnosis difficult. In this report, peculiar MR features in the presence of a connecting vessel between the normal deep venous system of the lower extremity and the tumour provide a clue for the early diagnosis of primary intraosseous AVM.

Efeito da fração não-oleosa doRicinus communisna biodistribuição comTecnécio-99m em camundongos / Effect of non-oily fraction ofRicinus communis on the bio distribution with Technetium-99m in mice

RESUMO Ricinus communisé uma planta pertence à família Euforbiaceae. A partir de seus frutos é extraído o óleo de rícino e outra fração altamente tóxica (fração não-oleosa). Neste estudo, foi avaliado o efeito da fração não oleosa de R. communis(FNORC) na biodistribuição do Tc-99m em camundongos sadios e em animais transplantados com Sarcoma-180 (S180). Para avaliação da biodistribuição do Tc-99m, o percentual de atividade radioativa total injetada (ATI%) foi mensurada utilizando um contador gama. Os resultados mostraram que, em animais sadios, houve aumento da captação do Tc-99m após o tratamento com FNORC pelos rins, cérebro e estômago. Apenas houve diminuição da absorção deste radioisótopo nos músculos. Em animais com tumor, houve redução significativa da captação do Tc-99m no coração, pulmões e tumor, e foi observado o aumento da captação apenas nos rins. Foi observada também a diminuição da concentração das proteínas plasmáticas totais em animais com tumor após tratamento com FNORC e atividade antitumoral significativa. Diante desses dados, conclui-se que fração não oleosa de R. communis possui atividade antitumoral significativa, porém altera a biodistribuição do Tc-99m, fato este que pode resultar em falhas nos processos de diagnóstico por imagem que utilizem este radioisótopo como marcador.

ABSTRACT Ricinus communis is a plant belonging to the Euforbiaceae family. From its fruits, it is extracted the castor oil and another highly toxic fraction (non-oily fraction). In this study, we evaluated the effect of the non-oily fraction of R. communis (NOFRC) on the bio distribution of Tc-99m in healthy mice and in animals transplanted with Sarcoma-180 (S180). To evaluate the bio distribution of theTc-99m, the percentage of the total injected radioactivity (% TIR) was measured through a gamma counter. There was an increase in the capitation of Tc-99m after the treatment with NOFRC in the kidneys, brain, and stomach of healthy animals. A decrease in the reception of this radionuclide was only found in the muscles. In animals with tumour, there was a significant reduction in the uptake of Tc-99m in the heart, lungs and tumour. An increase in the capitation was only observed in the kidneys. It was also observed a reduction in the total plasma protein concentration in animals with tumours after the treatment with NOFRC, besides significant antitumor activity. We concluded that there is antitumor activity in the NOFRC, but that it alters the biodistribution of Tc-99m, a fact which may result in failures in the diagnostic imaging process using this radioisotope as a marker.

Synthesis and preliminary evaluation of a new[99m]Tc labeled substance P analogue as a potential tumor imaging agent

Neurokinin 1 receptors [NK[1]R] are overexpressed on several types of important human cancer cells. Substance P [SP] is the most specific endogenous ligand known for NK1Rs. Accordingly,a new SP analogue was synthesized and evaluated for detection of NK[1]R positive tumors.[6-hydrazinopyridine-3-carboxylic acid [HYNIC]-Tyr[8]-Met[O][11]-SP] was synthesized and radiolabeled with 99mTc using ethylenediamine-N,N-diacetic acid [EDDA]and Tricine as coligands. Common physicochemical properties of radioconjugate were studied and in-vitro cell line biological tests were accomplished to determine the receptor mediated characteristics. In-vivo biodistribution in normal and tumor bearingnude mice was also assessed. The cold peptide was prepared in high purity [>99%] and radiolabeled with [99m]Tc at high specific activities [84-112GBq/ micro mol] with an acceptable labeling yield [>95%]. The radioconjugate was stable in-vitro in the presence of human serum and showed 44% protein binding to human serumalbumin. In-vitro cell line studies on U373MG cells showed an acceptable uptake up to 4.91 +/- 0.22% with the ratio of 60.21 +/- 1.19% for its specific fraction and increasing specific internalization during 4 h. Receptor binding assays on U373MG cells indicated a mean Kd of 2.46 +/- 0.43 nM and Bmax of 128925 +/- 8145 sites/cell. In-vivo investigations determined the specific tumor uptake in 3.36 percent of injected dose per gram [%ID/g] for U373MG cells and noticeable accumulations of activity in the intestines and lung. Predominant renal excretion pathway was demonstrated. Therefore, this new radiolabeled peptide could be a promising radiotracer for detection of NK[1]R positive primary or secondary tumors

The High Proportion of Painless Thyroiditis as a Cause of Thyrotoxicosis in Korea / 대한갑상선학회지

BACKGROUND AND OBJECTIVES: The most common cause of thyrotoxicosis is Graves' disease (GD), while painless thyroiditis (PT) comes in second. In Korea, the treatment of choice for GD is antithyroid drugs (ATDs). Since most cases of PT spontaneously improve, an accurate diagnosis is very important for the proper management of patients presenting with thyrotoxicosis. MATERIALS AND METHODS: Ninety-nine thyrotoxic patients were routinely checked with 99m Technetium (99mTc) thyroid scan except in pregnant or lactating women. We assessed the patients' clinical characteristics, serum levels of free T4 (FT4), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb), thyrotropin-binding inhibitory immunoglobulin (TBII), and findings of 99mTc thyroid scan. RESULTS: Among the 99 thyrotoxic patients, 69 were diagnosed with GD and 30 had PT. All of the patients with GD, diagnosed by scan, improved clinically and the thyroid hormone returned to normal with ATDs. All patients with PT improved spontaneously without ATDs. TPOAb and TGAb were positive in 13 (43.3%) and 20 (66.7%) patients with PT, respectively. TPOAb and TGAb were positive in 45 (65.2%) and 44 (63.8%) patients with GD, respectively. TBII was positive in only 73.5% of GD, and was entirely negative in the PT group. Mean FT4 level in GD was higher than in PT, but some patients with PT showed the highest level of FT4. CONCLUSION: PT accounted for a very high proportion of thyrotoxicosis in this study. All parameters investigated such as age, sex, goiter size or nature, level of FT4, TPOAb or TGAb, and TBII were unable to differentiate GD from PT. Considering the increased proportion of PT in the current study, we recommend routine thyroid scan in all thyrotoxic patients except in pregnant or lactating women.

Factors associated with reporting of abuse against children and adolescents by nurses within Primary Health Care / Fatores associados à notificação de maus-tratos em crianças e adolescentes realizada por enfermeiros na Atenção Primária à Saúde / Factores asociados a la notificación del maltrato en niños y adolescentes realizada por enfermeros en la Atención Primaria a la Salud

OBJECTIVE: to analyze the factors associated with the underreporting on the part of nurses within Primary Health Care of abuse against children and adolescents. METHOD: cross-sectional study with 616 nurses. A questionnaire addressed socio-demographic data, profession, instrumentation and knowledge on the topic, identification and reporting of abuse cases. Bivariate and multivariate logistic regression was used. RESULTS: female nurses, aged between 21 and 32 years old, not married, with five or more years since graduation, with graduate studies, and working for five or more years in PHC predominated. The final regression model showed that factors such as working for five or more years, having a reporting form within the PHC unit, and believing that reporting within Primary Health Care is an advantage, facilitate reporting. CONCLUSION: the study's results may, in addition to sensitizing nurses, support management professionals in establishing strategies intended to produce compliance with reporting as a legal device that ensures the rights of children and adolescents. .

OBJETIVO: analisar os fatores associados à notificação de maus-tratos em crianças e adolescentes, realizada por enfermeiros que atuam na Atenção Primária à Saúde. MÉTODO: estudo transversal, realizado com 616 enfermeiros. Foi utilizado um questionário contendo dados sociodemográficos, formação profissional, instrumentação e conhecimento sobre o tema, identificação e notificação de casos de maus-tratos. Análises bivariada e multivariada por regressão logística foram realizadas. RESULTADOS: predominaram enfermeiros do sexo feminino, na faixa etária entre 21 e 32 anos, não casados, com cinco ou mais anos de formado, com pós-graduação e com cinco ou mais anos de trabalho. O modelo logístico final evidenciou que fatores como tempo de trabalho de cinco ou mais anos, a unidade de saúde possuir a ficha de notificação, saber para onde encaminhar os casos, não ter medo de envolvimento legal e achar vantajosa a notificação na atenção primária facilitam a efetivação do ato notificatório. CONCLUSÃO: os resultados desta pesquisa, além de sensibilizar os enfermeiros para o problema, poderão ser utilizados pelos profissionais da gestão na orientação de estratégias para o cumprimento da notificação como dispositivo legal de garantia dos direitos de crianças e adolescentes. .

OBJETIVO: analizar los factores asociados a la notificación de maltrato en niños y adolescentes realizado por enfermeros que actúan en la Atención Primaria a la Salud. MÉTODO: estudio transversal realizado con 616 enfermeros. Fue utilizado un cuestionario conteniendo datos sociodemográficos, formación profesional, instrumentación y conocimiento sobre el tema, identificación, y notificación de casos de maltrato. Análisis bivariado y multivariado por regresión logística. RESULTADOS: predominaron enfermeros del sexo femenino, en la franja etaria de 21 a 32 años, no casados, con cinco o más años de graduación, con postgraduación y con cinco o más años de trabajo. El modelo logístico final evidenció que factores como tiempo de trabajo de cinco o más años, la unidad de salud poseer ficha de notificación, saber para donde encaminar los casos, no tener miedo de involucramiento legal y encontrar ventaja en la notificación en la atención primaria, son aspectos que facilitan la efectividad del acto de la notificación. CONCLUSIÓN: los resultados de esta investigación, además de sensibilizar a los enfermeros para el problema, podrán ser utilizados por profesionales de la gestión en la orientación de estrategias para el cumplimiento de la notificación como dispositivo legal de garantía de los derechos de niños y adolescentes. .