Linked Life Data

15068608

Source:http://linkedlifedata.com/resource/pubmed/id/15068608

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-4-7
pubmed:abstractText
The goal of this study was to synthesize and evaluate a novel bombesin (BN) analogue containing a polyethylene glycol (PEG) linker that can be radiolabeled with 64Cu through the DOTA bifunctional chelate. It is hypothesized that PEG linkers would improve the pharmacokinetics of radiolabeled bombesin analogues to optimize their tumor-to-normal tissue ratios for radiotherapy applications. The formation of this conjugate (DOTA-PEG-BN(7-14)) was confirmed by MALDI-TOF mass spectrometry and was radiolabeled with 64Cu at a specific activity of 2.7 MBq/nmol. DOTA-PEG-BN(7-14) bound specifically to gastrin-releasing peptide receptor (GRPR)-positive PC-3 cells with an IC50 value of 3.9 microM for displacing 125I-Tyr4-BN. Internalization of 64Cu-DOTA-PEG-BN(7-14) into PC-3 cells showed that 5.7%, 13.4%, and 21.0% was internalized at 0.5, 2, and 4 hours, respectively. Biodistribution of 64Cu-DOTA-PEGBN(7-14) was evaluated in normal, athymic nude mice 2, 4, and 24 hours after i.v. injection. This showed that most of the tissues had a similar uptake and clearance of 64Cu-DOTA-PEG-BN(7-14) compared to a control peptide with an alkyl linker (DOTA-Aoc-BN(7-14)) at the given time points. There was uptake of 10.8% ID/g of 64Cu-DOTA-PEG-BN(7-14) 4 hours after i.v. injection in the GRPR-positive pancreas that was inhibited to 2.4% upon injection of an excess of Tyr4-BN. These studies demonstrate that BN analogues can be conjugated with PEG linkers, radiolabeled with 64Cu, and bind to GRPR. Future studies will attempt to increase the affinity of these analogues for GRPR and alter the pharmacokinetics of the 64Cu-labeled conjugates through the use of various sized PEG linkers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1084-9785
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25-34
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
In vitro and in vivo evaluation of a 64Cu-labeled polyethylene glycol-bombesin conjugate.
pubmed:affiliation
Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, USA. rogers@radonc.wustl.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Evaluation Studies