title: Pharmacokinetics, dosimetry and comparative efficacy of 188Re-liposome and 5-FU in a CT26-luc lung-metastatic mice model.
abstract: The biodistribution, pharmacokinetics, dosimetry and comparative therapeutic efficacy of intravenously administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposome ((188)Re-liposome) and 5-FU were investigated in a CT26-luc lung-metastatic model. After intravenous administration of (188)Re-liposome, tumor accumulation from the radioactivity was observed. Levels of radioactivity in tumors were maintained at steady levels (from 5.40 to 5.67 %ID/g) after 4 to 24 h. In pharmacokinetics, the AUC((0→∞)), MRT((0→∞)) and Cl of (188)Re-liposome in blood via intravenous route were 998 h %ID/ml, 28.7 h and 0.1 ml/h, respectively. The total excreted fractions of feces and urine were 0.61 and 0.26, respectively. Absorbed doses for (188)Re-liposome in the liver and red marrow were 0.31 and 0.08 mSv/MBq, respectively. Tumor-absorbed doses for (188)Re-liposome ranged from 48.4 to 1.73 mGy/MBq at 10 to 300 g tumor spheres. In therapeutic efficacy, the survival times of mice after (188)Re-liposome [80% maximum tolerated dose (MTD); 29.6 MBq], 5-FU (80% MTD; 144 mg/kg), liposome or normal saline treatments were evaluated. Consequently, radiotherapeutics of (188)Re-liposome attained a longer lifespan (increase of 34.9%; P=.005) in mice than in the normal saline group. The increase in lifespan of the (188)Re-liposome group was 2.5-fold greater than that of the 5-FU group. Therefore, intravenous administration of (188)Re-liposome could provide a benefit and it is a promising strategy for delivery of passive nanotargeted radiotherapeutics in oncology applications.
authors.affiliation: Institute of Nuclear Energy Research, Taoyuan 325, Taiwan.
authors.forename: Liang-Cheng
authors.initials: LC
authors.lastname: Chen
authors.forename: Yu-Hsien
authors.initials: YH
authors.lastname: Wu
authors.forename: I-Hshiang
authors.initials: IH
authors.lastname: Liu
authors.forename: Chung-Li
authors.initials: CL
authors.lastname: Ho
authors.forename: Wan-Chi
authors.initials: WC
authors.lastname: Lee
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Chang
authors.forename: Keng-Li
authors.initials: KL
authors.lastname: Lan
authors.forename: Gann
authors.initials: G
authors.lastname: Ting
authors.forename: Te-Wei
authors.initials: TW
authors.lastname: Lee
authors.forename: Jui-Hung
authors.initials: JH
authors.lastname: Shien
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary / Q000628:therapy; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001853:Bone Marrow / Q000378:metabolism; D003110:Colonic Neoplasms / Q000473:pathology; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007275:Injections, Intravenous; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000556:secondary / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental; D011868:Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012211:Rhenium / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D008081:Liposomes; D011868:Radioisotopes; D012211:Rhenium; D005472:Fluorouracil