Liposomal Cu-64 labeling method using bifunctional chelators: Poly(ethylene glycol) spacer and chelator effects

Jai Seo, Lisa M. Mahakian, Azadeh Kheirolomoom, Hua Zhang, Claude F. Meares, Riccardo Ferdani, Carolyn J. Anderson, Katherine W. Ferrara

Research output: Contribution to journalArticle

39 Scopus citations

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 64Cu-TETA, 64Cu-TETA-PEG2k, and 64Cu-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 -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 64Cu-TETA and 64Cu-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 64Cu-TETA-chelated liposomes rather than 64Cu-CB-TE2A-chelated liposomes.

Original languageEnglish (US)
Pages (from-to)1206-1215
Number of pages10
JournalBioconjugate Chemistry
Volume21
Issue number7
DOIs
StatePublished - Jul 21 2010

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Organic Chemistry
  • Pharmaceutical Science
  • Biomedical Engineering
  • Pharmacology

Fingerprint Dive into the research topics of 'Liposomal Cu-64 labeling method using bifunctional chelators: Poly(ethylene glycol) spacer and chelator effects'. Together they form a unique fingerprint.

  • Cite this

    Seo, J., Mahakian, L. M., Kheirolomoom, A., Zhang, H., Meares, C. F., Ferdani, R., Anderson, C. J., & Ferrara, K. W. (2010). Liposomal Cu-64 labeling method using bifunctional chelators: Poly(ethylene glycol) spacer and chelator effects. Bioconjugate Chemistry, 21(7), 1206-1215. https://doi.org/10.1021/bc100018n