title: The pharmacokinetics of Zr-89 labeled liposomes over extended periods in a murine tumor model.
abstract: (89)Zr (t1/2=78.4h), a positron-emitting metal, has been exploited for PET studies of antibodies because of its relatively long decay time and facile labeling procedures. Here, we used (89)Zr to evaluate the pharmacokinetics of long-circulating liposomes over 168h (1week). We first developed a liposomal-labeling method using p-isothiocyanatobenzyl-desferrioxamine (df-Bz-NCS) and df-PEG1k-DSPE. Df-Bz-NCS was conjugated to 1mol% amino- and amino-PEG2k-DSPE, where the 1mol% df-PEG1k-DSPE was incorporated when the liposomes were formulated. Incubation of (89)Zr with df, df-PEG1k, and df-PEG2k liposomes for one hour resulted in greater than 68% decay-corrected yield. The loss of the (89)Zr label from liposomes after incubation in 50% human serum for 48h ranged from ~1 to 3% across the three formulations. Tail vein administration of the three liposomal formulations in NDL tumor-bearing mice showed that the (89)Zr label at the end of the PEG2k brush was retained in the tumor, liver, spleen and whole body for a longer time interval than (89)Zr labels located under the PEG2k brush. The blood clearance rate of all three liposomal formulations was similar. Overall, the results indicate that the location of the (89)Zr label altered the clearance rate of intracellularly-trapped radioactivity and that df-PEG1k-DSPE provides a stable chelation site for liposomal or lipid-based particle studies over extended periods of time.
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616, USA. Electronic address: jwseo@ucdavis.edu.
authors.forename: Jai Woong
authors.initials: JW
authors.lastname: Seo
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mahakian
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Tam
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
authors.forename: Shengping
authors.initials: S
authors.lastname: Qin
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Ingham
authors.affiliation: Department of Chemistry, University of California, Davis, CA 95616, USA.
authors.forename: Claude F
authors.initials: CF
authors.lastname: Meares
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616, USA. Electronic address: kwferrara@ucdavis.edu.
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Ferrara
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D003676:Deferoxamine / Q000737:chemistry; D004195:Disease Models, Animal; D004355:Drug Stability; D006801:Humans; D007553:Isotope Labeling; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics*; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging*; D051379:Mice; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D049268:Positron-Emission Tomography; D011868:Radioisotopes; D014018:Tissue Distribution; D015040:Zirconium
chemical_list: D008081:Liposomes; D010714:Phosphatidylethanolamines; D011868:Radioisotopes; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D015040:Zirconium; D003676:Deferoxamine
keywords: Deferoxamine; Liposomes; Positron emission tomography; Zr-89