BASE-LINE CONSIDERATION OF LIPOSOMAL CONTRAST AGENT - CNS TRANSPORT BY MACROPHAGES IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

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.