RESUMO
This work was designed to compare sentinel lymph node (SLN) uptake of 99mTc-labelled human serum albumin colloid (99mTc-HSAC), 99mTc-labelled antimony sulphur colloid (99mTc-SC) and a 99mTc-labelled dextran 70 solution (99mTc-Dx) and their selectivity in the identification of this node in the right rear footpad (RRF) of normal mice and tumour bearing mice. Radiopharmaceutical uptake in the SLN (popliteal lymph node) and the lumbar lymph node (LLN), the second lymphatic node station from RRF, were measured at different time points post-intradermal or intratumoural injection into the RRF of NIH normal mice and of Balb/c mice harbouring the murine mammary tumour M2. 99mTc-HSAC uptake in the SLN was significantly higher than LLN uptake. The 99mTc-SC demonstrated high uptake in SLN, but accumulation in LLN was also high. 99mTc-Dx showed low uptakes in both SLN and LLN. The intradermal injection resulted in a more effective radiopharmaceutical accumulation in SLN than did the intratumoural inoculation. Data also show that increments in tumour volume reduced radiopharmaceutical uptake in the SLN. Our results show that 99mTc-HSAC exhibits the highest uptake in the SLN combined with the smallest amounts of radiopharmaceutical passing through to the LLN. Therefore, 99mTc-HSAC appears to be the best radiopharmaceutical for sentinel node detection.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Antimônio , Dextranos , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Albumina Sérica , Compostos de Tecnécio , Adenocarcinoma/patologia , Animais , Antimônio/farmacocinética , Dextranos/farmacocinética , Feminino , Humanos , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos , Compostos de Organotecnécio/farmacocinética , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Biópsia de Linfonodo Sentinela , Albumina Sérica/farmacocinética , Compostos de Tecnécio/farmacocinética , Distribuição TecidualRESUMO
The anti-carcinoembryonic B2C114 monoclonal antibody was radiolabeled with 99mTc by a direct method and quality control tested in vitro by instant thin layer chromatography, gel column scanning and cellulose acetate electrophoresis and assessed in vivo for radioimmunodetection on a murine spontaneous mammary carcinoma. The optimal results of percent 99mTc bound to protein were obtained at a dithiothreitol:antibody molar ratio ranging from 800:1 to 1000:1 and at a methylene diphosphonate:stannous fluoride weight ratio of 4.3:1. Although cysteine removed up to 18% of the label during the first 4 h, the stability of the tracer appeared to be excellent in human serum at 37 degrees C and when challenged with DTPA. 99mTc-labeled B2C114 demonstrated good and specific in vivo tumor targeting.
Assuntos
Anticorpos Monoclonais , Marcação por Isótopo/normas , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Compostos de Organotecnécio , Animais , Anticorpos Monoclonais/farmacocinética , Antígeno Carcinoembrionário/imunologia , Humanos , Marcação por Isótopo/métodos , Neoplasias Mamárias Experimentais/diagnóstico , Camundongos , Camundongos Endogâmicos BALB C , Controle de Qualidade , Cintilografia , Distribuição TecidualRESUMO
Two anti-CEA antibodies, B2C114 and IORCEA1, were radiolabeled with 99mTc by two direct methods (mercaptoethanol and ascorbic acid reduction), and the radio-immunoimaging properties of B2C114 were assessed in mice bearing an M3-reactive tumor. The labeling efficiency was greater than 90% as measured by ITLC in saline, methylethylketone and with serum albumin impregnated sheets using ethanol: water: NH4OH (2:5:1). The label was stable to challenge with excess DTPA, and in the case of ascorbic acid reduction, serum analysis showed that 10-15% of the radioactivity was lost during incubation. In vitro studies demonstrated that the radiolabeled antibodies retained their immunoreactivity. Biodistribution studies in normal Balb/c mice showed that the pattern of uptake was quite similar for both antibodies. Biodistribution of the 99mTc-B2C114 and image studies in the animal model showed that the tumor was clearly visualized and that B2C114 labeled with 99mTc is a possible candidate for human radioimmunodetection of CEA-expressing tumors.