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 language | English (US) |
|---|---|
| Pages (from-to) | 1206-1215 |
| Number of pages | 10 |
| Journal | Bioconjugate Chemistry |
| Volume | 21 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 21 2010 |
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ASJC Scopus subject areas
- Biotechnology
- Bioengineering
- Organic Chemistry
- Pharmaceutical Science
- Biomedical Engineering
- Pharmacology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Liposomal Cu-64 labeling method using bifunctional chelators
T2 - Poly(ethylene glycol) spacer and chelator effects
AU - Seo, Jai
AU - Mahakian, Lisa M.
AU - Kheirolomoom, Azadeh
AU - Zhang, Hua
AU - Meares, Claude F.
AU - Ferdani, Riccardo
AU - Anderson, Carolyn J.
AU - Ferrara, Katherine W.
PY - 2010/7/21
Y1 - 2010/7/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77954866783&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954866783&partnerID=8YFLogxK
U2 - 10.1021/bc100018n
DO - 10.1021/bc100018n
M3 - Article
C2 - 20568726
AN - SCOPUS:77954866783
VL - 21
SP - 1206
EP - 1215
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 7
ER -