Rt. Stavraky et al., BASE-LINE CONSIDERATION OF LIPOSOMAL CONTRAST AGENT - CNS TRANSPORT BY MACROPHAGES IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS, Magnetic resonance imaging, 11(5), 1993, pp. 685-689
The purpose of this study was to investigate a specialized liposomal c
ontrast agent for magnetic resonance imaging (MRI), as part of a progr
am to examine infiltrating immune cells in lesions of experimental all
ergic encephalomyelitis (EAE). A potent investigational liposomal cont
rast agent, phosphatidylethanolamine-DTPA-gadolinium, was chosen which
has been shown to remain tightly liposomal-associated, with long pers
istence in vivo. Europium (Eu3+), a fluorescent paramagnetic metal, wa
s also utilized in these experiments in place of gadolinium. This mate
rial is avidly taken up by monocytes in vivo. Thirty-four animals rece
ived some form of liposomal material either before or during the openi
ng of the blood-brain barrier (BBB). Twenty-seven Hartley guinea pigs
were inoculated for EAE with homogenized brain and Complete Freunds Ad
juvant (CFA) and seven control animals received CFA alone. Eighty-two
percent of the experimental animals exhibited degeneration of the BBB
with inflammation and edema in the brain, while all control animals ha
d normal brain scans. T1-weighted MRI, performed to detect the presenc
e of liposomal contrast material in experimental animals, was not diff
erent from untreated animals. Fluorescent microscopy revealed no chara
cteristic changes associated with Eu3+ presence in the brains of treat
ed or control animals. Therefore, it would seem that insufficient mate
rial crosses the disrupted BBB, either in free form or subsequent to m
acrophage ingestion, to be detected by MRI or fluorescent microscopic
examination.