Baseline consideration of liposomal contrast agent. CNS transport by macrophages in experimental allergic encephalomyelitis.
The purpose of this study was to investigate a specialized liposomal contrast agent for magnetic resonance imaging (MRI), as part of a program to examine infiltrating immune cells in lesions of experimental allergic encephalomyelitis (EAE). A potent investigational liposomal contrast agent, phosphatidylethanolamine-DTPA-gadolinium, was chosen which has been shown to remain tightly liposomal-associated, with long persistence in vivo. Europium (Eu3+), a fluorescent paramagnetic metal, was also utilized in these experiments in place of gadolinium. This material is avidly taken up by monocytes in vivo. Thirty-four animals received some form of liposomal material either before or during the opening of the blood-brain barrier (BBB). Twenty-seven Hartley guinea pigs were inoculated for EAE with homogenized brain and Complete Freunds Adjuvant (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 had normal brain scans. T1-weighted MRI, performed to detect the presence of liposomal contrast material in experimental animals, was not different from untreated animals. Fluorescent microscopy revealed no characteristic changes associated with Eu3+ presence in the brains of treated or control animals. Therefore, it would seem that insufficient material crosses the disrupted BBB, either in free form or subsequent to macrophage ingestion, to be detected by MRI or fluorescent microscopic examination.
Stavraky
R T
RT
Physiology, Laboratory, Robarts Research Institute, University of Western Ontario, London, Canada.
Grant
C W
CW
Barber
K R
KR
Karlik
S J
SJ
D000818:Animals; D001812:Blood-Brain Barrier; D003287:Contrast Media; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D019786:Gadolinium DTPA; D006168:Guinea Pigs; D008264:Macrophages / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010714:Phosphatidylethanolamines / Q000493:pharmacokinetics
D003287:Contrast Media; D010714:Phosphatidylethanolamines; C082531:gadolinium phosphatidylethanolamine-DTPA; D004369:Pentetic Acid; D019786:Gadolinium DTPA