RESUMO
To evaluate the effectiveness of a single intratumoral dose of Pirocarbotrat, a gelatin-protected charcoal suspension labeled with chromic [32P]pyrophosphate, studies of bioelimination, biodistribution and therapeutic action were carried out in rats, and the results obtained were compared with those of other 32P dispersions. We found that 78.3% of the treated tumors reduced size after 32 days of treatment. At that time, the total eliminated activity was 12.70 +/- 3.90% distributed in urine (8.30 +/- 1.80%) and feces (4.40 +/- 3.50%). Biodistribution studies demonstrate that 84.50 +/- 2.60% of the injected activity remained in the tumor, with no significant concentration in the rest of the organism. We conclude that Pirocarbotrat can be used as a safe agent for brachytherapy of solid tumors with beta particles.
Assuntos
Partículas beta/uso terapêutico , Braquiterapia , Difosfatos/uso terapêutico , Neoplasias Mamárias Experimentais/radioterapia , Radioisótopos de Fósforo/uso terapêutico , Animais , Carvão Vegetal , Feminino , Gelatina , Neoplasias Mamárias Experimentais/induzido quimicamente , Metilnitrosoureia , Ratos , Ratos Sprague-DawleyRESUMO
In order to evaluate the effectiveness of an intratumorally single dose of chromic [32P] phosphate for the treatment of solid tumors, studies of bioelimination, biodistribution, and therapeutic action were carried out. Only for comparative purposes were similar studies undertaken using a solution of sodium [32P] orthophosphate-gelatin. Results show that when sodium [32P] orthophosphate-gelatin was intratumorally injected, the percentage of total elimination, after 32 days of treatment, was equal to 85.90 +/- 8.70%, with a higher percentage in urine (64.50 +/- 13.70%) than in feces (21.40 +/- 4.50%). In biodistribution studies, the greater percentage was found in bone (15.54 +/- 2.21%), whereas only 2.51 +/- 0.39% remained in the tumor. When chromic [32P] phosphate was intratumorally injected, we found that the total elimination was equal to 51.70 +/- 6.90%, with a higher amount in feces (32.70 +/- 4.80%) than in urine (19.00 +/- 3.60%). Biodistribution studies demonstrated that 28.93 +/- 1.30% was still in the tumor and 19.01 +/- 1.30% of the injected activity was found in the liver. On the other hand, when therapeutic action was evaluated, no tumoral regression was observed. These results demonstrate that the colloid of chromic [32P] phosphate cannot be used in the treatment of solid tumors as it mobilizes from the injection point, delivering a high dose to the entire organism.
Assuntos
Adenocarcinoma/radioterapia , Neoplasias Mamárias Experimentais/radioterapia , Fosfatos/farmacocinética , Fosfatos/uso terapêutico , Radioisótopos de Fósforo/farmacocinética , Radioisótopos de Fósforo/uso terapêutico , Adenocarcinoma/metabolismo , Animais , Compostos de Cromo , Coloides , Feminino , Neoplasias Mamárias Experimentais/metabolismo , Taxa de Depuração Metabólica , Ratos , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
The purpose of this work is to study the physicochemical properties of Pirocarbotrat to explain its radiopharmacological behavior. We also studied a mixture of charcoal plus chromic [32P]phosphate and charcoal plus sodium [32P]orthophosphate only for comparative purposes. The results show that the mean diameter of the Pirocarbotrat particles was 2.5 microm with an homogeneous distribution, while the other products show an heterogeneous distribution of the particle sizes, with a mean size diameter between 0.5 and 0.9 microm. Hydrolysis studies with a solution of 0.1 N HCl and with sulfochromic mixture revealed that in Pirocarbotrat the 32P is strongly bound to the charcoal particles. Bioelimination studies of Pirocarbotrat show that the total eliminated activity was 12.70 +/- 3.90%, with a higher amount in urine (8.30 +/- 1.80%) than in feces (4.40 +/- 3.50%). When biodistribution studies of Pirocarbotrat were carried out, we found that the 84.50 +/- 2.60% of the activity remained in the tumor with almost null irradiation of the other organs under study. When therapeutic action was evaluated, we observed that the percentage of tumor regression was 78.3% for the tumors injected with Pirocarbotrat. The other dispersions under study showed different behaviors with high activity percentages distributed throughout the organism. These studies demonstrate that Pirocarbotrat has the best radiopharmacological properties to ensure irradiation of the tumor with the least concomitant irradiation of surroundings or other organs or tissues.
Assuntos
Adenocarcinoma/metabolismo , Carvão Vegetal/química , Neoplasias Mamárias Experimentais/metabolismo , Fosfatos/farmacocinética , Radioisótopos de Fósforo/farmacocinética , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/radioterapia , Animais , Carvão Vegetal/farmacocinética , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/radioterapia , Taxa de Depuração Metabólica , Metilnitrosoureia , Fosfatos/uso terapêutico , Radioisótopos de Fósforo/uso terapêutico , Ratos , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
With the purpose of studying the effectivity of an intratumoral single dose of chromic [32P] phosphate (Phosphocol) for the treatment of solid tumors, studies of bioelimination, biodistribution and therapeutic action were carried out in rats with experimental induced tumors. The results show that the percentage of total elimination is equal to 29.76 +/- 9.60% with a higher percentage in faeces 23.28 +/- 8.81% than in urine 6.48 +/- 2.11%. Biodistribution studies show that, 51.61 +/- 5.82% of the injected activity is found in the tumor while in organs with reticuloendothelial cells, the percentage of activity was 13.09 +/- 5.15% in liver and 2.88 +/- 1.23% in lung. On the other hand, when therapeutic action was evaluated, we found that the percentage of tumor regression (P.T.R) was 61.0% for the injected tumors. It is important to point out that 4 of the treated animals show bioelimination patterns in which the elimination rises suddenly at some time of the study. These results demonstrate that the use of this kind of colloids is not to be recommended for the treatment of solid tumors with moderated degree of vascularization, since its mobilization from the injection point may result in the consequent irradiation of different organs that are not under treatment.
Assuntos
Adenocarcinoma/radioterapia , Braquiterapia , Cromo/uso terapêutico , Neoplasias Mamárias Experimentais/radioterapia , Fosfatos/uso terapêutico , Animais , Cromo/análise , Cromo/farmacocinética , Coloides , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Fosfatos/análise , Fosfatos/farmacocinética , Ratos , Ratos Sprague-DawleyRESUMO
With the purpose of studying the effectivity of an intratumoral single dose of chromic [32P] phosphate with great particles for the treatment of solid tumors, studies of bioelimination, biodistribution and therapeutic action were carried out. Only for comparative purposes, similar studies were undertaken using a solution of sodium -32P- orthophosphate-gelatine. The results show that when sodium [32P] orthophosphate-gelatine is used, the percentage of total elimination is (85.90 +/- 8.70)% with a higher percentage in urine (64.50 +/- 13.70)% than in faeces (21.40 +/- 4.50)%. In biodistribution studies, the greater percentage is found in bone (15.54 +/- 2.21)% while only a (2.51 +/- 0.39)% remains in the tumor. When great particles chromic [32P]phosphate was intratumorally injected, we determined that the total elimination is equal (36.28 +/- 6.27)%, finding a higher amount in faeces (29.44 +/- 5.26)% than in urine (6.84 +/- 2.21)%. Biodistribution studies demonstrated that (49.82 +/- 5.41)% remains in the tumor and (9.63 +/- 4.89)% of the injected activity is found in the liver. On the other hand, when therapeutic action was evaluated, we observed that the percentage of tumor regression (P.T.R.) is 52.0% for the tumors injected with chromic [32P]phosphate and 0.0% for those injected with sodium [32P]orthophosphate-gelatine. These results show that the great particles colloid of chromic [32P]phosphate is not safe enough for the treatment of solid tumors, since it is mobilized from the injection point, delivering a high dose to the whole organism.
Assuntos
Adenocarcinoma/radioterapia , Compostos de Cromo/uso terapêutico , Neoplasias Mamárias Experimentais/radioterapia , Fosfatos/uso terapêutico , Animais , Compostos de Cromo/administração & dosagem , Compostos de Cromo/farmacocinética , Fezes/química , Feminino , Injeções , Fosfatos/administração & dosagem , Fosfatos/farmacocinética , Ratos , Ratos Sprague-Dawley , Indução de Remissão , Resultado do Tratamento , Urina/químicaRESUMO
With the purpose studying the effectivity of an intratumoral single dose of chromic [(32)P] phosphate with great particles for the treatment of solid tumors, studies of biolimination, biodistribution and therapeutic action were carried out. Only for comparative purpose, similar studies were undertaken using a solution of sodium [(32)P] orthophosphategelatine. The results show that when sodium [(32)P] orthophosphategelatine is used, the percentage of total elimination is (85.90+8,70) per cent with a higler percentage in urine (64.50+13.70) per cent than in faeces (21.40+4.50) per cent. In biodistribution studies, the greater percentage is found in bone (15.54+2.21) per cent while only a (2.51+0.39) per cent remains in the tumor. When great particles chromic [(32)P] phosphate was intratumorally injected, we determined that the total elimination is equal (36.28+6.27) per cent, finding a higler amount in faeces (29.44+5.26) per cent than in urine (6.84+2.21) per cent. Biodistribution studies demonstrated that (49.82+5.41) per cent remains in the tumor and (9.63+4.89) per cent of the injected activity is found in the liver. On the other hand, when therapeutic action was evoluted, we observed that the percentage of tumor regression (P.T.R) is 52.0 per cent for the tumors injected with chromic [(32)P] phosphate and 0.0 per cent for those injected with sodium [(32)P] orthophosphate-gelatine. These results show that the great particles colloid of chromic [(32)P] phosphate is not safe enough for the tratment of solid tumors, since it is mobilezed from the injection point, delivering a high dose to the whole organism.
Assuntos
Animais , Ratos , Feminino , Adenocarcinoma/radioterapia , Compostos de Cromo/uso terapêutico , Neoplasias Mamárias Experimentais/radioterapia , Fosfatos/uso terapêutico , Radioisótopos de Fósforo/uso terapêutico , Sódio/uso terapêutico , Compostos de Cromo/administração & dosagem , Compostos de Cromo/farmacocinética , Coloides , Fezes/química , Injeções , Fosfatos/administração & dosagem , Fosfatos/farmacocinética , Radioisótopos de Fósforo/administração & dosagem , Radioisótopos de Fósforo/farmacocinética , Ratos Sprague-Dawley , Indução de Remissão , Sódio/administração & dosagem , Sódio/farmacocinética , Resultado do Tratamento , Urina/químicaRESUMO
Diez pacientes con diagnóstico de aplasia medular adquirida (AM) recibieron globulina antilinfocitaria (GAL) como tratamiento. Dos pacientes eran niños de dos yocho años de edad y el resto eran adultos con una media de 32 años (rango 16-56). El intervalo medio desde el diagnóstico hasta el inicio del tratamiento fue de 5,38 meses (rango 1-20. Cinco pacientes tenían antecedentes de contacto con benceno, organofosforado y piroxicam/ampicilina. Otro paciente tenía diagnóstico ce hemoglobinuria paroxística nocturna. En los cuatro restantes no se pudo determinar la etiología. Nueve pacientes habían recibido tratamiento previamente, seis con corticoides y andrógenos y res sólo con corticoides, sin respuesta. La GAL fue administrada bajo internación, en dosis de 10-20 mg/Kg/día durante cuatro días endos pacientes y en el resto durante ocho días. Entre el séptimo y el décimo día de comenzado el tratamiento, todos los pacientes desarrollaron enfermedad del suero, que fue controlada con prednisona. A los tres meses, tres pacientes tuvieron respuesta completa, y tres pacientes respuesta parcial. Cuatro pacientes no respondieron y de ellos tres fallecierom dos por sepsis y uno por hemorragia intracerebral. Nuestros resultados demuestran una respuesta completa o parcial en el 60% de los pacientes tratados con GAL, por lo que concluimos que la GAL es una opción terapéutica eficaz para el tratamiento de la AM severa o moderada en ausencia de posibilidad de transplante de médula ósea