Linked Life Data

16078851

Source:http://linkedlifedata.com/resource/pubmed/id/16078851

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2005-8-4
pubmed:abstractText
Previous studies with the anilinoquinazoline epidermal growth factor receptor (EGFR) irreversible inhibitor [(11)C]-ML03 demonstrated a rapid metabolism of the tracer, which led to its low in vivo accumulation in EGFR overexpressing tumors. To enhance tumor uptake, the chemical structure of the compound was modified, and four new groups of EGFR inhibitors with a wide range of chemical reactivities were synthesized. Chemical reactivity assay of the compounds, performed with reduced glutathione (GSH), revealed that the group C (4-(dimethylamino)-but-2-enoic amide) derivative was the least chemically reactive against the nucleophilic attack of GSH. Nonetheless, it demonstrated a high inhibitory potency and bound irreversibly to the EGFR. Consequently, the blood stability of the group C compound (5a, ML04) labeled with (11)C was studied. In a time frame of 60 min, no radioactive metabolites were detected in blood. The stability of [(11)C]-5a, as indicated both from in vitro blood-stability assays and injection into nude rats, was significantly higher as compared to [(11)C]-ML03. Since group C presented a greater promise for tumor accumulation, it represents, to date, the most suitable candidate for radiolabeling with long-lived positron emission tomography (PET) radioisotopes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5337-48
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
High-affinity epidermal growth factor receptor (EGFR) irreversible inhibitors with diminished chemical reactivities as positron emission tomography (PET)-imaging agent candidates of EGFR overexpressing tumors.
pubmed:affiliation
Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120, Israel. mishani@md.huji.ac.il
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't