Abstract
1477
Objectives: This study evaluated the biodistribution and pharmacokinetics of passive targeted 111In-Vinorelbine-pegylated liposomes (IVNBPL) after intraperitoneal (i.p.) and intravenous (i.v.) injections in a C26/tk-luc colon carcinoma ascites mouse model. The tumor lesions in peritoneal cavity were also monitored and confirmed by 124I-FIAU/microPET imaging. Methods: The VNB-pegylated liposomes were labeled with 111In-oxine and the radiochemical purity was determined with gel chromatography method. BALB/c mice were received 2×105 C26/tk-luc cells by subcutaneous injection below the dorsal flank. Normal mice and C26/tk-luc colon carcinoma ascites mice were injected i.p or i.v of IVNBPL (3.7 MBq; 2.5 mg VNB/kg body weight). The pharmacokinetics and cumulated radioactivity in organs were derived from the results of biodistribution studies. Results: The labeling yield and radiochemical purity of IVNBPL were over 90%. In vitro stability of IVNBPL in human plasma at 37°C for 72 h was more than 85%. Tumor lesions and ascites were confirmed by 124I-FIAU/microPET and ultrasound on day 11 after tumor inoculation. The cumulated radioactivity (expressed as area under the curve, AUC) after i.p injection of IVNBPL into tumor-bearing mice was high in ascites (3.95-fold), comparable in tumor (1.02-fold), and low in liver (0.63-fold), spleen (0.35-fold) and blood (0.27-fold) compared with those after i.v injection. The higher accumulation of IVNBPL in ascites, comparable uptake in tumor and less retention of IVNBPL in the blood and critical organs (liver, spleen, etc.) via i.p. injection indicates the i.p. administration of 111In-Vinorelbine-pegylated liposomes may have a more efficacious therapeutic effect and cause lower toxicity in most normal organs. Conclusions: Our findings provide important information for establishing an optimal treatment protocol when i.p. injection with 111In-VNB-pegylated liposomes on a C26/tk-luc colon carcinoma ascites mouse model is applied to cancer therapy of intraperitoneal malignant disease.
- Society of Nuclear Medicine, Inc.