RESUMEN
Nanoliposomes are useful carriers in drug delivery. Radiolabeled nanoliposomes have potential applications in radiotherapy and diagnostic imaging. In this study, the biodistribution and pharmacokinetics of 188Re-BMEDA-labelled pegylated liposomes (RBLPL) and unencapsulated 188Re-BMEDA administered by the i.v. route in murine C26-colon tumour-bearing mice were investigated. MicroSPECT/CT images were performed to evaluate the distribution and tumor targeting of RBLPL in mice. For the biodistribution study, the highest uptake of liposome in tumors was 3.62% +/- 0.73% at 24 h after RBLPL administration, and the tumor to muscle ratio of RBLPL was 7.1-fold higher than that of 188Re-BMEDA. With image analysis, the highest SUV in tumor was 2.81 +/- 0.26 at 24 h after injection of RBLPL. The Pearson correlation analysis showed a positive correlation of tumor targeting or uptake of RBLPL between biodistribution and microSPECT semi-quantification imaging analysis (r = 0.633). The results of the pharmacokinetics revealed that the area under the tissue concentration-time curve (AUC) of RBLPL was 4.7-fold higher than that of unencapsulated 188Re-BMEDA. These results suggested the potential benefit and advantage of 188Re-labeled nanoliposomes for imaging and treatment of malignant diseases.
Asunto(s)
Neoplasias del Colon/metabolismo , Etilenodiaminas/administración & dosificación , Etilenodiaminas/farmacocinética , Compuestos Organometálicos/administración & dosificación , Compuestos Organometálicos/farmacocinética , Radiofármacos/administración & dosificación , Radiofármacos/farmacocinética , Animales , Línea Celular Tumoral , Neoplasias del Colon/diagnóstico por imagen , Modelos Animales de Enfermedad , Estabilidad de Medicamentos , Etilenodiaminas/química , Marcaje Isotópico , Liposomas , Masculino , Ratones , Ratones Endogámicos BALB C , Compuestos Organometálicos/química , Radioisótopos , Radiofármacos/química , Renio/química , Distribución Tisular , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Histological methods are used to define the growth and response to various treatments of lung carcinoma in mice. The aim of the study was to evaluate a quantitative and 3D-tomographic microPET/microCT dual-image modality using 18F-fluorodeoxyglucose (FDG) to monitor the tumor progression in an experimental metastasis mouse model. MATERIALS AND METHODS: Six normal mice were subjected to FDG-microPET/microCT image scan to present the normal thorax morphology. Twenty-one 8-week-old male C57BL/6 mice were inoculated with 1 x 10(6) Lewis lung carcinoma cells (LLC1) through the lateral tail vein. FDG-microPET/microCT scans were performed on days 0, 5, 9, 13 and 18 (n=6) to monitor the growth of the tumor. MicroPET and microCT images were further used to monitor the metastasis of the lung carcinoma to the liver. Fifteen mice were sacrificed for biodistribution on days 0, 5, 9, 13 and 18 after the inoculation of lung carcinoma cells. RESULTS: The FDG-microPET/microCT dual-image modality showed that the growth of the tumor could be monitored longitudinally. The standard uptake value (SUV) of FDG increased from 0.63 +/- 0.05 on day 0 to 1.03 +/- 0.15 on day 18, reflecting the growth of the tumor in mice. The tumors located in the lung and liver could be clearly visualized by the fusion of microPET and microCT images, and further confirmed by whole-body autoradiography or H&E stain. CONCLUSION: By FDG-microPET, the increase in SUV provided an alternative for assessing the growth of a tumor in vivo. Our results suggest that the growth progression of lung carcinoma can be identified using the FDG-microPET/microCT dual-image modality longitudinally in mice.