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Ion-pairing interactions between 99mTc-based myocardial imaging agents and oleic acid

Heard, Charles Martin and Hadgraft, Jonathan 1996. Ion-pairing interactions between 99mTc-based myocardial imaging agents and oleic acid. Pharmaceutical Research 13 (2) , pp. 316-323.

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Abstract

PURPOSE: The purpose was to test the hypothesis that ion-paired facilitated transport is of importance in successful myocardial uptake of cationic imaging complexes. In vitro ion-pairing interactions between oleic acid and seven cationic technetium-99m complexes based on the ligands 1,2-bis[bis(2-ethoxyethyl) phosphino ethane] (tetrofosmin), 1,2-bis(dimethyl phosphino ethane) (DMPE) and 1,2-bis(diethyl phosphino ethane) (DEPE) has been studied. The complexes studied were: [99mTc O2 (tetrafosmin)2]+ (commercially available as myocardial perfusion imaging kit, Myoview), [99mTc O2 (DMPE)2]+, [99mTc O2 (DEPE)2]+, [99mTc Cl2 (DMPE)2]+, [99mTc Cl2 (DEPE)2]+, [99mTc (DMPE)3]+ and [99mTc (DEPE)3]+. METHODS: Ion-pairing interactions were monitored using a rotating diffusion cell containing a solid supported liquid membrane and by formation of lipid monolayers. RESULTS: Depletion of complex from the donor phase into an isopropyl myristate model membrane was generally in proportion to distribution coefficient and transfer to the receptor compartment was in all cases very small. However, by the inclusion of 5% w/v oleic acid, which is used in myocardial metabolism, partitioning was enhanced by amounts which varied depending on the tendency to form complex/oleate ion-pairs. Transfer to the receptor compartment was increased for most complexes when given sufficient time to diffuse through the membrane. The complex [99mTc O2 (tetrofosmin)2]+ appeared to form particularly stable ion-pairs with oleic acid. Monolayer formation also indicated ion-pairing interactions. CONCLUSIONS: The results suggested that whether or not a complex is taken up by the myocyte may depend on its ability to 'hitch a ride' by ion-pairing with the myocytes energy source--a molecule of long chain fatty acid.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Publisher: Springer Verlag
ISSN: 0724-8741
Last Modified: 04 Jun 2017 07:44
URI: http://orca.cf.ac.uk/id/eprint/67513

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