title: Pharmacokinetics, micro-SPECT/CT imaging and therapeutic efficacy of (188)Re-DXR-liposome in C26 colon carcinoma ascites mice model.
abstract: The pharmacokinetics and internal radionuclide therapy of intraperitoneally administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin ((188)Re-DXR-liposome) were investigated in the C26 murine colon carcinoma ascites mouse model. After intraperitoneal administration of the nanotargeted bimodality (188)Re-DXR-liposome, the ascites and tumor accumulation of the radioactivity were observed, the levels of radioactivity within the ascites were maintained at relatively higher levels before 48 h and the levels of radioactivity in the tumor were maintained at steady levels after 4 h. The AUC((o-->infinity)) of (188)Re-DXR-liposome in blood, ascites and tumor was 9.3-, 4.2- and 4.7-fold larger than that of (188)Re-BMEDA, respectively. The maximum tolerated dose of intraperitoneally administrated (188)Re-DXR-liposome was determined in normal BALB/c mice. The survival, tumor and ascites inhibition of mice after (188)Re-DXR-liposome (22.2 MBq of (188)Re, 5 mg/kg of DXR) treatment were evaluated. Consequently, radiochemotherapeutics of (188)Re-DXR-liposome attained better survival time, tumor and ascites inhibition (decreased by 49% and 91% at 4 days after treatment; P<.05) in mice than radiotherapeutics of (188)Re-liposome or chemotherapeutics of Lipo-Dox did. Therefore, intraperitoneal administration of novel (188)Re-DXR-liposome could provide a benefit and promising strategy for delivery of passive nanotargeted bimodality radiochemotherapeutics in oncology applications.
authors.affiliation: Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: Liang-Cheng
authors.initials: LC
authors.lastname: Chen
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Chang
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Yu
authors.forename: Ya-Jen
authors.initials: YJ
authors.lastname: Chang
authors.forename: Yu-Hsien
authors.initials: YH
authors.lastname: Wu
authors.forename: Wan-Chi
authors.initials: WC
authors.lastname: Lee
authors.forename: Chung-Hsin
authors.initials: CH
authors.lastname: Yeh
authors.forename: Te-Wei
authors.initials: TW
authors.lastname: Lee
authors.forename: Gann
authors.initials: G
authors.lastname: Ting
mesh_terms: D000818:Animals; D001201:Ascites / Q000628:therapy*; D001345:Autoradiography; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004355:Drug Stability; D007553:Isotope Labeling; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D008807:Mice, Inbred BALB C; D036103:Nanotechnology; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011868:Radioisotopes / Q000627:therapeutic use*; D012211:Rhenium / Q000627:therapeutic use*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D011868:Radioisotopes; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D012211:Rhenium; D004317:Doxorubicin