RESUMEN
This study demonstrates high-efficiency sterilisation of single cancer cells in a SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio-immunotherapy with 5.5 MBq labelled antibody conjugate (1.11 GBq/mg) 2 days after an intravenous graft of 5.10(6) Daudi cells resulted in tumour-free survival for >120 days in 89% of treated animals. In contrast, all control mice (no treatment or treated with 5 or 300 micro g unlabelled rituximab) developed lymphoma disease. At the end of the study period, 28.4%+/-4% of the long-lived daughter activity remained in the body, of which 91.1% was located in bone tissue and 6.3% in the liver. A relatively high daughter radioactivity concentration was found in the spleen (12%+/-2%/g), suggesting that the killed cancer cells are mainly eliminated through the spleen. This promising preliminary in vivo study suggests that targeted alpha therapy with (149)Tb is worthy of consideration as a new-generation radio-immunotherapeutic approach.
Asunto(s)
Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales/uso terapéutico , Leucemia/metabolismo , Leucemia/radioterapia , Radioinmunoterapia/métodos , Partículas alfa/uso terapéutico , Animales , Anticuerpos Monoclonales de Origen Murino , Antineoplásicos/uso terapéutico , Apoptosis/efectos de la radiación , Línea Celular Tumoral , Supervivencia Celular/efectos de la radiación , Relación Dosis-Respuesta a Droga , Sistemas de Liberación de Medicamentos/métodos , Medicina Basada en la Evidencia/métodos , Femenino , Leucemia/tratamiento farmacológico , Ratones , Ratones SCID , Especificidad de Órganos , Radiofármacos/uso terapéutico , Reproducibilidad de los Resultados , Rituximab , Sobrevida , Distribución Tisular , Resultado del TratamientoRESUMEN
A straightforward quantitative method for gas chromatography-mass spectrometry determination of isosorbide 5-mononitrate (IS5MN) and its related impurities such as isosorbide (IS), isosorbide diacetate (ISDA) and isosorbide 2-acetate-5-nitrate (IS2A5N) in raw materials as well as in dosage formulations is developed. The recovery of these materials was found to be 100.4 +/- 2.4, 99.3 +/- 4.7, 97.8 +/- 5.2 and 100.1 +/- 3.1%, while the detection limits were 27.2, 1.26, 1.02 and 0.78 micrograms in dosage formulations for IS5MN, ISDA, IS2A5N, and IS, respectively. The applicability of the method was tested by analysing three different formulations of IS5MN.