title: Biodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice.
abstract: BACKGROUND
  Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of (188)Re-labeled nanoliposomes ((188)Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated.
  
  
  METHODS
  Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered (188)Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of (188)Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with (188)Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared.
  
  
  RESULTS
  In biodistribution, the highest uptake of (188)Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 ± 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of (188)Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of (188)Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the (188)Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with (188)Re-liposomes provided better survival time (increased by 34.6% of life span; P < 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P < 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU).
  
  
  CONCLUSIONS
  The use of (188)Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently clinically applied chemotherapeutics drug 5-FU in a colonic peritoneal carcinomatosis mouse model. This result suggests that (188)Re-liposomes have potential benefit and are safe in treating peritoneal carcinomatasis of colon cancer.
authors: Institute of Nuclear Energy Research, Taoyuan, Taiwan, ROC.
authors: Chia-Che
authors: CC
authors: Tsai
authors: Chih-Hsien
authors: CH
authors: Chang
authors: Liang-Cheng
authors: LC
authors: Chen
authors: Ya-Jen
authors: YJ
authors: Chang
authors: Keng-Li
authors: KL
authors: Lan
authors: Yu-Hsien
authors: YH
authors: Wu
authors: Chin-Wei
authors: CW
authors: Hsu
authors: I-Hsiang
authors: IH
authors: Liu
authors: Chung-Li
authors: CL
authors: Ho
authors: Wan-Chi
authors: WC
authors: Lee
authors: Hsiao-Chiang
authors: HC
authors: Ni
authors: Tsui-Jung
authors: TJ
authors: Chang
authors: Gann
authors: G
authors: Ting
authors: Te-Wei
authors: TW
authors: Lee
mesh_terms: D000818:Animals; D001201:Ascites / Q000378:metabolism / Q000473:pathology; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007275:Injections, Intravenous; D053208:Kaplan-Meier Estimate; D008081:Liposomes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010534:Peritoneal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011829:Radiation Dosage; D011868:Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012211:Rhenium / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D055114:X-Ray Microtomography; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium; D005472:Fluorouracil