RESUMO
Glucocorticoid (GC) hormone has been commonly used to treat systemic inflammation and immune disorders. However, the side effects associated with long-term use of high-dose GC hormone limit its clinical application seriously. GC hormone that can specifically target the lung might decrease the effective dosage and thus reduce GC-associated side effects. In this study, we successfully prepared human lung-targeting liposomal methylprednisolone crosslinked with nanobody (MPS-NSSLs-SPANb). Our findings indicate that MPS-NSSLs-SPANb may reduce the effective therapeutic dosage of MPS, achieve better efficacy, and reduce GC-associated side effects. In addition, MPS-NSSLs-SPANb showed higher efficacy and lower toxicity than conventional MPS.
Assuntos
Fibrose Pulmonar Idiopática/tratamento farmacológico , Metilprednisolona/administração & dosagem , Metilprednisolona/farmacologia , Proteína A Associada a Surfactante Pulmonar/administração & dosagem , Proteína A Associada a Surfactante Pulmonar/farmacologia , Animais , Química Farmacêutica , Portadores de Fármacos/química , Ensaio de Imunoadsorção Enzimática , Humanos , Lipossomos/química , Pulmão/efeitos dos fármacos , Masculino , Camundongos , Camundongos Nus , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Anticorpos de Domínio Único/administração & dosagem , Anticorpos de Domínio Único/farmacologiaRESUMO
Accurate determination of human epidermal growth factor receptor 2 (HER2) expression is essential for HER2-targeted therapy in patients with cancer. HER2 expression in a complex environment, such as in a heterogeneous tumor, makes the precise assessment of the HER2 status difficult using current methods. In this study, we developed a novel 99mTc-labeled anti-HER2 single-domain antibody (99mTc-NM-02) as a molecular imaging tracer for the noninvasive detection of HER2 expression and investigated its safety, radiation dosimetry, biodistribution, and tumor-targeting potential in 10 patients with breast cancer. Our data showed that no drug-related adverse reactions occurred. The tracer mainly accumulated in the kidneys and liver with mild uptake in the spleen, intestines, and thyroid; however, only background tracer levels were observed in other organs where primary tumors and metastases typically occurred. The mean effective dose was 6.56 × 10-3 mSv/MBq, and tracer uptake was visually observed in the primary tumors and metastases. A maximal standard uptake value of 1.5 was determined as a reasonable cutoff for identifying HER2 positivity using SPECT/CT imaging. Our 99mTc-NM-02 tracer is safe for use in breast cancer imaging, with reasonable radiation doses, favorable biodistribution, and imaging characteristics. 99mTc-NM-02 SPECT imaging may be an accurate and noninvasive method to detect the HER2 status in patients with breast cancer.
Assuntos
Neoplasias da Mama/diagnóstico , Compostos Radiofarmacêuticos/administração & dosagem , Receptor ErbB-2/análise , Anticorpos de Domínio Único/administração & dosagem , Adulto , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Imagem Molecular/métodos , Compostos Radiofarmacêuticos/farmacocinética , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tecnécio , Distribuição TecidualAssuntos
Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/economia , Custos de Medicamentos , Pandemias/economia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/economia , Administração por Inalação , Animais , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/economia , Betacoronavirus/genética , COVID-19 , Camelídeos Americanos/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Doença pelo Vírus Ebola/tratamento farmacológico , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Humanos , Evasão da Resposta Imune/genética , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , SARS-CoV-2 , Anticorpos de Domínio Único/administração & dosagem , Anticorpos de Domínio Único/economia , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/uso terapêutico , Glicoproteína da Espícula de Coronavírus/imunologia , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência , Tratamento Farmacológico da COVID-19RESUMO
Acquired thrombotic thrombocytopenic purpura is a rare blood disorder with a high early mortality rate, if untreated. Standard of care plasma exchange and glucocorticoids have dramatically improved survival. However, additional advancements are necessary to further decrease mortality. Caplacizumab-yhdp (Cablivi®) is the first Food and Drug Administration-approved treatment indicated for adult patients with acquired thrombotic thrombocytopenic purpura, in combination with plasma exchange and immunosuppressive therapy. However, there are considerable risks associated with the use of caplacizumab and they must be weighed against the benefits of the medication.