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 Citations (Scopus)

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

Fingerprint

Ethylene Glycol
Liposomes
Radioactivity
Chelating Agents
Labeling
Polyethylene glycols
Liver
Blood
Spleen
Brushes
Lipids
Assays
Acids
Serum
(4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)copper(II)

ASJC Scopus subject areas

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

Cite this

Seo, J., Mahakian, L. M., Kheirolomoom, A., Zhang, H., Meares, C. F., Ferdani, R., ... 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

Liposomal Cu-64 labeling method using bifunctional chelators : Poly(ethylene glycol) spacer and chelator effects. / Seo, Jai; Mahakian, Lisa M.; Kheirolomoom, Azadeh; Zhang, Hua; Meares, Claude F.; Ferdani, Riccardo; Anderson, Carolyn J.; Ferrara, Katherine W.

In: Bioconjugate Chemistry, Vol. 21, No. 7, 21.07.2010, p. 1206-1215.

Research output: Contribution to journalArticle

Seo, J, Mahakian, LM, Kheirolomoom, A, Zhang, H, Meares, CF, Ferdani, R, Anderson, CJ & Ferrara, KW 2010, 'Liposomal Cu-64 labeling method using bifunctional chelators: Poly(ethylene glycol) spacer and chelator effects', Bioconjugate Chemistry, vol. 21, no. 7, pp. 1206-1215. https://doi.org/10.1021/bc100018n
Seo, Jai ; Mahakian, Lisa M. ; Kheirolomoom, Azadeh ; Zhang, Hua ; Meares, Claude F. ; Ferdani, Riccardo ; Anderson, Carolyn J. ; Ferrara, Katherine W. / Liposomal Cu-64 labeling method using bifunctional chelators : Poly(ethylene glycol) spacer and chelator effects. In: Bioconjugate Chemistry. 2010 ; Vol. 21, No. 7. pp. 1206-1215.
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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.",
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AU - Meares, Claude F.

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