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

Chen, Liang-Cheng; Chang, Chih-Hsien; Yu, Chia-Yu; Chang, Ya-Jane; Hsu, Wei-Chuan; Ho, Chung-Li; Yeh, Chung-Hsin; Luo, Tsai-Yueh; Lee, Te-Wei; Ting, Gann

doi:10.1016/j.nucmedbio.2007.02.003

« Previous Next »Nuclear Medicine and Biology
Volume 34, Issue 4 , Pages 415-423, May 2007

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

Liang-Cheng Chen
- Institute of Nuclear Energy Research, Taoyuan, Taiwan
Chih-Hsien Chang
- Institute of Nuclear Energy Research, Taoyuan, Taiwan
Chia-Yu Yu
- Institute of Nuclear Energy Research, Taoyuan, Taiwan
Ya-Jane Chang
- Institute of Nuclear Energy Research, Taoyuan, Taiwan
Wei-Chuan Hsu
- Institute of Nuclear Energy Research, Taoyuan, Taiwan
Chung-Li Ho
- Institute of Nuclear Energy Research, Taoyuan, Taiwan
Chung-Hsin Yeh
- Institute of Nuclear Energy Research, Taoyuan, Taiwan
Tsai-Yueh Luo
- Institute of Nuclear Energy Research, Taoyuan, Taiwan
Te-Wei Lee
- Institute of Nuclear Energy Research, Taoyuan, Taiwan
Gann Ting
- National Health Research Institutes, Miaoli, Taiwan
- Corresponding author. National Institute of Cancer Research, National Health Research Institutes, A191Ward, Veterans General Hospital-Taipei 201, Sec. 2, Beitou Taipei 112, Taiwan, ROC. Tel.: +886 2 28712121; fax: +886 2 28716467.

Received 3 November 2006; received in revised form 16 January 2007; accepted 8 February 2007.

Abstract

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 ¹⁸⁸Re-N,N-bis (2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA)-labeled pegylated liposomes (RBLPL) and unencapsulated ¹⁸⁸Re-BMEDA after intraperitoneal (ip) injection in a C26 colon carcinoma ascites mouse model. The nanopegylated liposomes were labeled with ¹⁸⁸Re-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°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 ¹⁸⁸Re-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 ¹⁸⁸Re-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.

Keywords: Biodistribution, Micro-SPECT/CT, Pegylated liposomes, Pharmacokinetics, Rhenium-188