These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Boronic acid adducts of technetium dioxime (BATO) complexes derived from quinuclidine benzilate (QNB) boronic acid stereoisomers: syntheses and studies of their binding to the muscarinic acetylcholine receptor.
    Author: Jurisson SS, Pirro J, DiRocco RJ, Rosenspire KC, Jagoda E, Nanjappan P, Eckelman WC, Nowotnik DP, Nunn AD.
    Journal: Nucl Med Biol; 1995 Apr; 22(3):269-81. PubMed ID: 7627141.
    Abstract:
    We have investigated the possibility of using BATO complexes derivatized with the muscarinic acetylcholine receptor (mAChR) antagonist, quinuclidinyl benzilate (QNB), for mAChR imaging. The BATO complexes, TcCl(DMG)3B-QNB, were prepared using QNB derivatives containing a 4'-boronic acid substituent on one of the benzilic benzene rings (QNB-boronic acid). The QNB-boronic acid molecule has two chiral centers, and all four QNB-BATO stereoisomers were made and evaluated. When studied using in vitro receptor binding assays based on tissue from rat brain caudate-putamen (which contains primarily M1 and M4 mAChR) and rat heart (M2 mAChR), the QNB-boronic acid stereoisomers had binding affinities (KA) in the range 2 x 10(5)-1 x 10(8), at least 10-fold lower than the KA for QNB (ca 2 x 10(9)). The stereochemistry of both centers had some influence on the affinity constant. When the TcCl(DMG)3B-QNB complexes were studied, none of the stereoisomeric complexes displayed measurable specific binding (KA < 10(6)), but all showed high non-specific binding. In vitro autoradiography with rat brain slices confirmed the absence of specific binding in these tracers. In vivo, the 99mTcCl(DMG)3B-QNB complexes displayed minimal brain uptake, and modest heart uptake; the latter was unlikely to be related to uptake by the mAChR. In light of these findings, we conclude that the interaction between the TcCl(DMG)3B-QNB complexes and biological membranes is dominated by the hydrophobicity of the BATO moiety. The TcCl(DMG)3B-QNB complexes, therefore, have little potential for mAChR imaging.
    [Abstract] [Full Text] [Related] [New Search]