Ion-pairing interactions between 99MTc-based myocardial imaging agents and oleic acid.
OBJECTIVE
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.
Heard
C M
CM
Welsh School of Pharmacy, UWC, Cardiff, United Kingdom.
Hadgraft
J
J
D002412:Cations; D002463:Cell Membrane Permeability; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006321:Heart / Q000000981:diagnostic imaging*; D008567:Membranes, Artificial; D009206:Myocardium / Q000378:metabolism*; D019301:Oleic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D010720:Phosphines / Q000737:chemistry / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D013329:Structure-Activity Relationship
D002412:Cations; D008567:Membranes, Artificial; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D010720:Phosphines; C041972:technetium Tc 99m-bis(1,2-diethylphosphino)ethane; D019301:Oleic Acid; C031898:technetium Tc 99m bis(1,2-dimethylphosphino)ethane