Linked Life Data

21244039

Source:http://linkedlifedata.com/resource/pubmed/id/21244039

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-2-16
pubmed:abstractText
Robust chelating stability under biological condi-tions is critical for the design of copper-based radiopharmaceuticals. In this study, the stabilities of (64)Cu-DOTA and diamsar (two bifunctional Cu-64 chelators (BFCs)) conjugated DGEA peptides were evaluated. The in vitro stabilities of (64)Cu-DOTA-DGEA, (64)Cu-DOTA-Ahx-DGEA, and (64)Cu-Z-E(diamsar)-Ahx-DGEA were evaluated in PBS. A carboxyl-protected DOTA-DGEA was also synthesized to study the potential inter- and intramolecular interactions between DOTA and the carboxylate groups of DGEA peptide. microPET imaging of (64)Cu-DOTA-DGEA and (64)Cu-Z-E(diamsar)-Ahx-DGEA were performed in PC-3 prostate tumor model to further investigate the in vivo behavior of the tracers. DOTA-DGEA, DOTA-Ahx-DGEA, Z-E(diamsar)-Ahx-DGEA, and protected DOTA-DGEA peptides were readily obtained, and their identities were confirmed by MS. (64)Cu(2+) labeling was performed with high radiochemical yields (>98%) for all tracers after 1 h incubation. Stability experiments revealed that (64)Cu-DOTA-DGEA had unexpectedly high (64)Cu(2+) dissociation when incubated in PBS (>55% free (64)Cu(2+) was observed at 48 h time point). The (64)Cu(2+) dissociation was significantly reduced in the carboxyl-protected (64)Cu-DOTA-DGEA complex but not in the (64)Cu-DOTA-Ahx-DGEA complex, which suggests the presence of competitive binding for (64)Cu(2+) between DOTA and the carboxyl groups of the DGEA peptide. In contrast, no significant (64)Cu(2+) dissociation was observed for (64)Cu-Z-E(diamsar)-Ahx-DGEA in PBS. For microPET imaging, the PC-3 tumors were clearly visualized with both (64)Cu-DOTA-DGEA and (64)Cu-Z-E(diamsar)-Ahx-DGEA tracers. However, (64)Cu-DOTA-DGEA demonstrated 5× higher liver uptake than (64)Cu-Z-E(diamsar)-Ahx-DGEA. This biodistribution variance could be attributed to the chelating stability difference between these two tracers, which correlated well with the PBS stability experiments. In summary, the in vitro and in vivo evaluations of (64)Cu-Z-E(diamsar)-Ahx-DGEA and (64)Cu-DOTA-DGEA have demonstrated the significantly superior Cu-chelation stability for the diamsar derivative compared with the established DOTA chelator. The results also suggest that diamsar may be preferred for Cu chelation especially when multiple carboxylic acid groups are present. Free carboxyl groups may naturally compete with DOTA for (64)Cu(2+) binding and therefore reduce the complex stability.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1520-4812
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
256-63
pubmed:meshHeading
pubmed-meshheading:21244039-Animals, pubmed-meshheading:21244039-Cell Line, Tumor, pubmed-meshheading:21244039-Copper Radioisotopes, pubmed-meshheading:21244039-Heterocyclic Compounds, pubmed-meshheading:21244039-Heterocyclic Compounds, 1-Ring, pubmed-meshheading:21244039-Humans, pubmed-meshheading:21244039-Integrin alpha2beta1, pubmed-meshheading:21244039-Male, pubmed-meshheading:21244039-Mice, pubmed-meshheading:21244039-Mice, Inbred BALB C, pubmed-meshheading:21244039-Mice, Nude, pubmed-meshheading:21244039-Oligopeptides, pubmed-meshheading:21244039-Organometallic Compounds, pubmed-meshheading:21244039-Positron-Emission Tomography, pubmed-meshheading:21244039-Prostatic Neoplasms, pubmed-meshheading:21244039-Sarcosine, pubmed-meshheading:21244039-Tissue Distribution, pubmed-meshheading:21244039-Xenograft Model Antitumor Assays
pubmed:year
2011
pubmed:articleTitle
Biological stability evaluation of the ?2?1 receptor imaging agents: diamsar and DOTA conjugated DGEA peptide.
pubmed:affiliation
Molecular Imaging Center, Department of Radiology, University of Southern California, Los Angeles, California 90033, United States.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't