title: Liposomal Cu-64 labeling method using bifunctional chelators: poly(ethylene glycol) spacer and chelator effects.
abstract: Two bifunctional Cu-64 chelators (BFCs), (6-(6-(3-(2-pyridyldithio)propionamido)hexanamido)benzyl)-1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA-PDP) and 4-(2-(2-pyridyldithioethyl)ethanamido)-11-carboxymethyl-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane (CB-TE2A-PDEA), were synthesized and conjugated to long-circulating liposomes (LCLs) via attachment to a maleimide lipid. An in vitro stability assay of (64)Cu-TETA, (64)Cu-TETA-PEG2k, and (64)Cu-CB-TE2A-PEG2k liposomes showed that more than 86% of the radioactivity remains associated with the liposomal fraction after 48 h of incubation with mouse serum. The in vivo time activity curves (TAC) for the three liposomal formulations showed that approximately 50% of the radioactivity cleared from the blood pool in 16-18 h. As expected, the in vivo biodistribution and TAC data obtained at 48 h demonstrate that the clearance of radioactivity from the liver slows with the incorporation of a poly(ethylene glycol)-2k (PEG2k) brush. Our data suggest that (64)Cu-TETA and (64)Cu-CB-TE2A are similarly stable in the blood pool and accumulation of radioactivity in the liver and spleen is not related to the stability of Cu-64 chelator complex; however, clearance of Cu-64 from the liver and spleen are faster when injected as (64)Cu-TETA-chelated liposomes rather than (64)Cu-CB-TE2A-chelated liposomes.
authors.affiliation: Department of Chemistry , University of California, Davis, California 95616, USA.
authors.forename: Jai Woong
authors.initials: JW
authors.lastname: Seo
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mahakian
authors.forename: Azadeh
authors.initials: A
authors.lastname: Kheirolomoom
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Claude F
authors.initials: CF
authors.lastname: Meares
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ferdani
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Anderson
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Ferrara
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D003301:Copper Radioisotopes / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008301:Maleimides / Q000737:chemistry; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry*; D049268:Positron-Emission Tomography; D013194:Staining and Labeling; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D003301:Copper Radioisotopes; D008081:Liposomes; D008301:Maleimides; D011092:Polyethylene Glycols