In vitro and in vivo response of PSMA-617 radiolabeled with CA and NCA lutetium-177.

The PSMA-targeted radionuclide therapy has been explored since 2015 with radioisotope lutetium-177, whose ß- emission range is adequate for micrometastases treatment. This radioisotope is obtained by two different production routes that directly affect the specific activity of lutetium-177 (non-carrier added and carrier added) and, consequently, the specific activity of radiopharmaceuticals, like 177Lu-PSMA-617. The influence of the specific activity of lutetium-177 on the properties of the radiopharmaceutical PSMA-617 was evaluated through pre-clinical studies. The in vitro study pointed to a lower constant of dissociation with non-carrier added lutetium-177 due to the difference in the specific activity. However, competition and internalization assays resulted in similar results for both lutetium-177. Based on these pre-clinical experiments, the total in vitro tumor cell binding and tumor uptake in vivo were similar, with no influence of the specific activity of the 177Lu-PSMA-617. Regardless the specific activity did not directly affect tumor uptake, the tumor/non-target organs ratios were higher for the radiopharmaceutical labeled with carrier added lutetium-177, which had the lowest specific activity.

89Zr-DFO-Cetuximab as a Molecular Imaging Agent to Identify Cetuximab Resistance in Head and Neck Squamous Cell Carcinoma.

Background: Despite the improvement in clinical outcomes for head and neck squamous cell carcinoma (HNSCC) as the result of cetuximab, patients may present with or develop resistance that increases tumor recurrence rates and limits clinical efficacy. Therefore, identifying those patients who are or become resistant is essential to tailor the best therapeutic approach. Materials and Methods: Cetuximab was conjugated to p-NCS-Bz-DFO and labeled with 89Zr. The resistance model was developed by treating FaDu cells with cetuximab. Western blotting (WB) and specific binding assays were performed to evaluate epidermal growth factor receptor (EGFR) expression and 89Zr-DFO-cetuximab uptake in FaDu cetuximab-resistant (FCR) and FaDu cetuximab-sensitive (FCS) cells. Positron emission tomography imaging and biodistribution were conducted in NU/NU nude mice implanted with FCR or FCS cells. Results: Cetuximab was successfully radiolabeled with 89Zr (≥95%). Binding assays performed in FCR and FCS cells showed significantly lower 89Zr-DFO-cetuximab uptake in FCR (p < 0.0001). WB suggests that the resistance mechanism is associated with EGFR downregulation (p = 0.038). This result is in agreement with the low uptake of 89Zr-DFO-cetuximab in FCR cells. Tumor uptake of 89Zr-DFO-cetuximab in FCR was significantly lower than FCS tumors (p = 0.0340). Conclusions: In this work, the authors showed that 89Zr-DFO-cetuximab is suitable for identification of EGFR downregulation in vitro and in vivo. This radiopharmaceutical may be useful for monitoring resistance in HNSCC patients during cetuximab therapy.

Development of radioimmunoconjugate for diagnosis and management of head-and-neck subclinical cancer and colorectal carcinoma

ABSTRACT Scientific innovations in diagnostic methods are important drivers of cancer control and prevention. Noninvasive imaging of the epidermal growth factor receptor (EGFR) in head-and-neck squamous, cell carcinoma and colorectal cancer could be valuable to select patients for EGFR-targeted therapy, as well as to monitor the efficacy and occurrence of resistance to immunotherapy. In order to develop the first Brazilian radioimmunoconjugate for diagnosis, Cetuximab has been conjugated to p-SCN-Bn-DTPA chelator and radiolabeled with Indium-111. The conjugation methodology was optimized using different mAb:DTPA molar ratios, time was then reduced for immunoconjugate preparation, besides the protein recovery' percentage increased after purification (m = 83.8 ± 0.91 %). The stability of Cetuximab-DTPA at - 20 oC was evaluated for six months, and its integrity was greater than 90% (m =93.9 ± 1.5%, N = 24). The radioimmunoconjugate with specific activity of 185 MBq/mg showed radiochemical purity above 95% (m=96.8 ± 1.31 %, N = 15). We conclude that the radioimmunoconjugate 111In-DTPA-cetuximab is stable and may be applied to the diagnosis of EGFR-positive tumors.

A FDG-18F na distinção de placa aterosclerótica: inovação em tecnologia PET/CT / FDG-18F in differentiating atherosclerotic plaque: innovation in PET/CT technology

A composição da placa aterosclerótica, em contrapartida ao grau de estenose arterial, parece ser o determinante crítico da vulnerabilidade e trombogenicidade da placa. O fluordesoxiglucose (FDG-18F), pode ser usado para obter imagensda atividade celular inflamatória de forma não invasiva através da tecnología PET. O objetivo principal do presente estudo foi averiguar a viabilidade da tecnologia FDG-18F PET na avaliação do processo inflamatório instalado nas placas ateroscleróticas, e, dessa forma, promover a distinção de placas ateroscleróticas através da relação entre acúmulo do radiofármaco e as características funcionais da lesão aterosclerótica. Estudo epidemiológico prospectivo, duplo cego randomizado, transversal foi realizado em cinco pacientes, seis controles e, os mesmos, foram submetidos ao exame diagnóstico FDG-18F PET/CT. Os valores de suv em artérias carótidas e veias jugulares do próprio paciente e o comparativo com o grupo controle foram correlacionados através de uma avaliação qualitativa do coeficiente de correlação de pearson. Através de um estudo descritivo comparativo inter-grupos na carótida direita observa-se que 64.9% da média dos valores de SUV corresponde aos pacientes em estudo. Na análise efetuada intra-grupo da carótida direita com a jugular direita dos pacientes em estudo, observou-se um valor médio de SUV 26.2% superior na artéria carótida. No grupo controle, a diferença entre os níveis médios de captação do FDG-18F foi inferior a 10%. Através da endarterectomia, foi possível realizar um estudo anátomo patológico e, dessa forma, identificar a presença de conteúdo inflamatórionas carótidas avaliadas, caracterizando assim placas instáveis. A tecnologia FDG-18F PET mostrou-se exequível favorecendo uma boa correlação histopatológica entre o processo inflamatório instalado nas placas ateroscleróticas e os níveis mensurados de SUV.

An ethological approach to the study of behavioral disorders provides key information on functionalaspects of behavior that characterize certain pathologies. The purpose of this study was to describe non-verbal behavioral units presented by a group of 14 women with social phobia (SP) and a control groupof 13 women during a clinical interview and to evaluate the possible differences between these twogroups. The 19 behavior units were selected with the index of concordance between the observers tauKendall = 0.795 (p = 0.000). People with SP supported the way they spoke with their hands and placedtheir hands on their legs, in comparison with the control group. People with SP nodded more often,touched their faces, pressed their lips, licked their lips and touched their hair more frequently than thecontrol group. The article suggests that a systematic evaluation of non-verbal behavior may be impor-tant in conducting a full evaluation of patients with SF in a clinical environment, and may contribute toevaluating the efficiency of the treatment.

A FDG-18F na distinþÒo de placa aterosclerótica: inovaþÒo em tecnologia PET/CT / FDG-18F in differentiating atherosclerotic plaque: innovation in PET/CT technology

A composiþÒo da placa aterosclerótica, em contrapartida ao grau de estenose arterial, parece ser o determinante crítico da vulnerabilidade e trombogenicidade da placa. O fluordesoxiglucose (FDG-18F), pode ser usado para obter imagensda atividade celular inflamatória de forma nÒo invasiva através da tecnología PET. O objetivo principal do presente estudo foi averiguar a viabilidade da tecnologia FDG-18F PET na avaliaþÒo do processo inflamatório instalado nas placas ateroscleróticas, e, dessa forma, promover a distinþÒo de placas ateroscleróticas através da relaþÒo entre acúmulo do radiofármaco e as características funcionais da lesÒo aterosclerótica. Estudo epidemiológico prospectivo, duplo cego randomizado, transversal foi realizado em cinco pacientes, seis controles e, os mesmos, foram submetidos ao exame diagnóstico FDG-18F PET/CT. Os valores de suv em artérias carótidas e veias jugulares do próprio paciente e o comparativo com o grupo controle foram correlacionados através de uma avaliaþÒo qualitativa do coeficiente de correlaþÒo de pearson. Através de um estudo descritivo comparativo inter-grupos na carótida direita observa-se que 64.9% da média dos valores de SUV corresponde aos pacientes em estudo. Na análise efetuada intra-grupo da carótida direita com a jugular direita dos pacientes em estudo, observou-se um valor médio de SUV 26.2% superior na artéria carótida. No grupo controle, a diferenþa entre os níveis médios de captaþÒo do FDG-18F foi inferior a 10%. Através da endarterectomia, foi possível realizar um estudo anátomo patológico e, dessa forma, identificar a presenþa de conteúdo inflamatórionas carótidas avaliadas, caracterizando assim placas instáveis. A tecnologia FDG-18F PET mostrou-se exequível favorecendo uma boa correlaþÒo histopatológica entre o processo inflamatório instalado nas placas ateroscleróticas e os níveis mensurados de SUV. (AU)

An ethological approach to the study of behavioral disorders provides key information on functionalaspects of behavior that characterize certain pathologies. The purpose of this study was to describe non-verbal behavioral units presented by a group of 14 women with social phobia (SP) and a control groupof 13 women during a clinical interview and to evaluate the possible differences between these twogroups. The 19 behavior units were selected with the index of concordance between the observers tauKendall = 0.795 (p = 0.000). People with SP supported the way they spoke with their hands and placedtheir hands on their legs, in comparison with the control group. People with SP nodded more often,touched their faces, pressed their lips, licked their lips and touched their hair more frequently than thecontrol group. The article suggests that a systematic evaluation of non-verbal behavior may be impor-tant in conducting a full evaluation of patients with SF in a clinical environment, and may contribute toevaluating the efficiency of the treatment.(AU)

Cardiovascular risk factors in children and adolescents living in an urban area of Southeast of Brazil: Ouro Preto Study.

This study aims to identify risk factors for cardiovascular disorders in schoolchildren living in Ouro Preto City, Brazil. A cross-sectional study was carried out in a population-based sampling of schoolchildren (6-14 years old), randomly selected and stratified by the proportion of students according to age and gender in each schools of the city. Biochemical, clinical and anthropometric variables as well as physical activity and family history were used in a logistic regression model for obesity or arterial hypertension. Out of 780 schoolchildren sampled, the risk of obesity was greater in subjects presenting high triglyceride and low high density lipoprotein-cholesterol levels, and those whose parents were obese, while the risk of hypertension was high in obese subjects and those who presented low birth weight. It was observed that 44.4% of the schoolchildren were exposed to two or three cardiovascular disease (CVD) risk factors and 8.2% were exposed to four or six factors. These findings should be considered in preventive measures to reduce the future risk for CVD among schoolchildren in Brazil.