Linked Life Data

15186598

Source:http://linkedlifedata.com/resource/pubmed/id/15186598

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-6-9
pubmed:abstractText
Two neuropeptides, bombesin (BBS) and neurotensin (NT) and their radiolabeled analogues, have great potential for tumour targeting, either for diagnosis (e.g., with 99mTc) or therapy (e.g., with 90Y or 188Re). In this study, we investigated NT(8-13) and BBS(7-14) analogues with Nalpha-histidinyl acetate linked to the N-terminus of the peptide. This His-derivative forms a stable and inert tridentate complex with the 99mTc(CO)3 and the 188Re(CO)3 moieties. The stability of 99mTc-labeled neurotensin and bombesin analogues was tested in human plasma samples and in tumour cell cultures in the presence and absence of specific enzyme inhibitors. The inhibitor of ACE (angiotensin converting enzyme) was the most effective in inhibiting the peptide cleavage of both NT(8-13) and BBS(7-14). In agreement with this finding, the replacement of Ile12 by tert-leucine (NT) and Leu13 by cyclohexylalanin (BBS) brought about a better stability. With NT(8-13) analogues, higher tumour to nontarget (t/nt) ratios and the same affinity to the receptor was observed, but with BBS(7-14) derivatives the affinity was lower and the t/nt ratio was not significantly improved. Toxicity tests showed no effect in mice of up to a five-hundred-fold higher dose than planned for patient application, which started successfully with NT(8-13) analogues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1084-9785
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
181-8
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Improving the tumor uptake of 99mTc-labeled neuropeptides using stabilized peptide analogues.
pubmed:affiliation
Center for Radiopharmaceutical Science, Paul Scherrer Institut, Villigen, Switzerland.
pubmed:publicationType
Journal Article