RESUMO
INTRODUCTION: Radiosynovectomy (RS) with 90Y-hydroxyapatite (90Y-HyA) aims to control knee hemarthrosis in hemophiliac patients to prevent secondary arthropathy. However, knee RS using 153Sm-hydroxyapatite (153Sm-HyA) is considered less suitable due to the lower average soft tissue range and energy of 153Sm for large joints, such as the knees. PURPOSE: The objective of this investigation was to assess the efficacy and safety of knee RS with 153Sm-HyA, compared to 90Y-HyA. METHODS: Forty patients were prospectively assigned to undergo knee RS with 153Sm-HyA (n = 19) or with 90Y-HyA (n = 21). The frequency of hemarthrosis episodes before and after treatment were compared. RESULTS: After six months of knee RS, 153Sm-HyA and 90Y-HyA promoted a similar reduction of hemarthrosis episodes (50% and 66.7%, respectively). However, after 12 months of knee RS, the reduction of hemarthrosis episodes was significantly (p = 0.037) higher using 153Sm-HyA (87.5%) compared to 90Y-HyA (50.0%). This discrepancy was more pronounced (p = 0.002) for 153Sm-HyA compared to 90Y-HyA in adults/adolescents. CONCLUSION: Knee radiosynovectomy with 153Sm-HyA is safe, reduces hemarthrosis episodes after 12 months of treatments, especially in adults/adolescents and even with grades III/IV arthropathy, similar to 90Y-HyA. 90Y-HyA seems to promote better hemarthrosis control in small children.
Assuntos
Durapatita/química , Hemartrose/radioterapia , Articulação do Joelho/efeitos da radiação , Radioisótopos/química , Samário/química , Radioisótopos de Ítrio/química , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radioisótopos/efeitos adversos , Radioisótopos/uso terapêutico , Medição de Risco , Samário/efeitos adversos , Samário/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversos , Radioisótopos de Ítrio/uso terapêuticoRESUMO
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.
Assuntos
Cetuximab/farmacologia , Desferroxamina/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias de Cabeça e Pescoço/patologia , Imagem Molecular/métodos , Radioisótopos/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Zircônio/metabolismo , Animais , Apoptose , Proliferação de Células , Cetuximab/administração & dosagem , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Camundongos , Camundongos Nus , Compostos Radiofarmacêuticos/metabolismo , Sideróforos/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Distribuição Tecidual , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Estudos recentes têm demonstrado que o radiofármaco L, L-ECD-99mTc apresenta estabilidade in vitro e características favoráveis para o estudo da perfusäo cerebral. O presente trabalho descreve a obtençäo de conjuntos reativos liofilizados de L, L-ECD para pronta marcaçäo com 99mTc, compostos de 1mg de L,LECD, 0,125 mg de SnCl2.2H2O,24,0 mg de manitol e 0,36 mg de EDTA em pH 2,0-3,0. Os conjuntos reativos estéreis e apirogênicos apresentam estabilidade superior a 4 meses quando estocados em condiçöes ideais, mostrando-se estáveis após a marcaçäo por período superior a 4 h. Os estudos de distribuiçäo biológica em camundongos mostram rápido clareamento sanguíneo e a habilidade do complexo de atravessar a barreira hemato-encefálica. As captaçöes cardíaca e pulmonar säo inexpressivas e o complexo é eliminado pelas vias renal e intestinal. As imagens estáticas planares anterior e lateral mostram uma captaçäo intensa e persistente do complexo no cérebro do cachorro