Investigation of microenvironmental factors influencing the longitudinal relaxation times of drugs and other compounds.
The aim of this study was to investigate the microenvironmental factors likely to influence the longitudinal relaxation time of MR visible drugs or compounds in vivo at 1.5 T. The relative influence that viscosity, albumin and paramagnetic contrast agent concentrations have on the observed longitudinal relaxation times of three 19F MR detectable drugs and compounds have been investigated. Our data show that for 5-fluorouracil, flucloxacillin and tetrafluorosuccinic acid-containing phantoms, the presence of albumin at normal physiological concentrations will have relaxation effects of the same order of magnitude as that of a commonly clinically administered contrast agent, gadolinium diethylenetriamine pentaacetic acid. The contribution of viscosity is shown, in the examples studied here, to be of minor importance, contributing less than 6.5% to the observed relaxation effects. It is also demonstrated that in the presence of competitive binding of other ligands for common binding sites on albumin, the 19F longitudinal relaxation time of 5-fluorouracil can increase by up to 340% from its value in the absence of the competing ligand. The relevance of the findings to in vivo studies is discussed.
Cancer Research UK Clinical Magnetic Resonance Research Group, Institute of Cancer Research, Sutton, Surrey, SM2 5PT. andrzej.s.dzik-jurasz@gsk.com
A S K
AS
Dzik-Jurasz
M O
MO
Leach
I J
IJ
Rowland
D000418:Albumins / Q000032:analysis; D001241:Aspirin / Q000032:analysis* / Q000737:chemistry; D003287:Contrast Media / Q000032:analysis* / Q000737:chemistry; D005436:Floxacillin / Q000032:analysis* / Q000737:chemistry; D005466:Fluorocarbons / Q000032:analysis* / Q000737:chemistry; D005472:Fluorouracil / Q000032:analysis* / Q000737:chemistry; D019786:Gadolinium DTPA / Q000032:analysis; D008279:Magnetic Resonance Imaging / Q000379:methods*; D019047:Phantoms, Imaging; D011485:Protein Binding; D013386:Succinates / Q000032:analysis* / Q000737:chemistry; D014783:Viscosity
D000418:Albumins; D003287:Contrast Media; D005466:Fluorocarbons; D013386:Succinates; C060763:perfluorosuccinic acid; D005436:Floxacillin; D019786:Gadolinium DTPA; D001241:Aspirin; D005472:Fluorouracil