Biodistribution, pharmacokinetics and imaging of (188)Re-BMEDA-labeled pegylated liposomes after intraperitoneal injection in a C26 colon carcinoma ascites mouse model.
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.
Chen
Liang-Cheng
LC
Institute of Nuclear Energy Research, Taoyuan, Taiwan.
Chang
Chih-Hsien
CH
Yu
Chia-Yu
CY
Chang
Ya-Jane
YJ
Hsu
Wei-Chuan
WC
Ho
Chung-Li
CL
Yeh
Chung-Hsin
CH
Luo
Tsai-Yueh
TY
Lee
Te-Wei
TW
Ting
Gann
G
D000818:Animals; D001345:Autoradiography; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging*; D004337:Drug Carriers; D005029:Ethylenediamines / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D007091:Image Processing, Computer-Assisted; D007274:Injections, Intraperitoneal; D007553:Isotope Labeling; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
C521828:188Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine; D004337:Drug Carriers; D005029:Ethylenediamines; D008081:Liposomes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D011092:Polyethylene Glycols