RADIOIMAGING MOIETIES COUPLED TO PEPTIDEASE-BINDING MOIETIES FOR IMAGING TISSUES AND ORGANS THAT EXPRESS PEPTIDASES
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United States of America Patent
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Issued Date -
Sep 4, 2008
app pub date -
Aug 29, 2007
filing date -
Aug 29, 2006
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Abandoned
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Abstract
Conjugates, methods and kits are described for imaging tissues and organs that express one or more peptidases. In a preferred embodiment of the invention, a series of di-(2-pyridylmethyl)amine (D) ligands, which can bind M(CO).sub.3.sup.+ [M=Tc or Re], were coupled to lisinopril (L). Aliphatic tethers with varying number of methylene groups (3, 4, 5, and 7; D(C.sub.4)L, D(C.sub.5)L, D(C.sub.6)L, and D(C.sub.8)L, respectively) were utilized, with in vitro inhibitory activity increasing with increasing number of methylene groups. The D(C.sub.8)L conjugate was observed to be significantly more potent than D(C.sub.4)L. In vivo specificity for ACE was studied in both tissue distribution and gamma imaging studies, demonstrating localization in tissues with high ACE content. Localization was blocked by pretreatment with lisinopril.
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