Biodistribution, pharmacokinetics and imaging of 188Re-BMEDA-labeled pegylated liposomes after intraperitoneal injection in a C26 colon carcinoma ascites mouse model

• DOI: 10.1016/j.nucmedbio.2007.02.003
• Publication Date: 2007-05-24T07:45:12Z
• Authors: Liang-Cheng Chen; Chih-Hsien Chang; Chia-Yu Yu; Ya-Jane Chang; Wei-Chuan Hsu; Chung-Li Ho; Chung-Hsin Yeh; Tsai-Yueh Luo; Te-Wei Lee; Gann Ting
• Keywords: Male; Tomography, Emission-Computed, Single-Photon; Drug Carriers; Mice, Inbred BALB C; Ethylenediamines; Polyethylene Glycols; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Isotope Labeling; Colonic Neoplasms; Liposomes; Image Processing, Computer-Assisted; Organometallic Compounds; Animals; Autoradiography; Tissue Distribution; Radiopharmaceuticals; Tomography, X-Ray Computed; Injections, Intraperitoneal; Neoplasm Transplantation

Nanoliposomes are important carriers capable of packaging drugs for various delivery applications through passive targeting tumor sites by enhanced permeability and retention effect. Radiolabeled liposomes have potential applications in radiotherapy and diagnostic imaging. The purpose of this study was to investigate the biodistribution, pharmacokinetics and imaging of nanotargeted (188)Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomes (RBLPL) and unencapsulated (188)Re-BMEDA after intraperitoneal (ip) injection in a C26 colon carcinoma ascites mouse model. The nanopegylated liposomes were labeled with (188)Re-BMEDA. The labeling efficiency of RBLPL was 82.3+/-4.5%. In vitro stability of RBLPL in normal saline at room temperature and in rat plasma at 37 degrees C for 72 h was 92.01+/-1.31% and 82.4+/-1.64%, respectively. The biodistribution studies indicated that the radioactivity in ascites was 69.96+/-14.08 percentage injected dose per gram (% ID/g) at 1h to 5.99+/-1.97% ID/g at 48 h after ip administration of RBLPL. The levels of radioactivity in tumor were progressive accumulation to a maximum of 6.57+/-1.7% ID/g at 24 h. The radioactivity of (188)Re-BMEDA in ascites reached the maximum level of 54.89+/-5.91% ID/g at 1 h and declined rapidly with time. Pharmacokinetic studies revealed that the terminal half-life, total body clearance and area under the curve of RBLPL were 5.3-, 9.5- and 9.4-fold higher than that of (188)Re-BMEDA in blood, respectively. These results suggested that the long circulation, bioavailability and localization of RBLPL in tumor and ascites sites, which also demonstrate that the ip administration of RBLPL is a potential multifunctional nanoradiotherapeutics and imaging agents on a C26 colon carcinoma ascites mouse model.