Biodistribution and clearance of contrast-carrying MREV liposomes.
Contrast-carrying liposomes (CCLs) have been shown to increase the attenuation coefficient of the liver and spleen during computed tomographic (CT) imaging. A modification of the reverse-phase evaporation preparative technique ("MREV") led to production of CCLs that entrap contrast media efficiently. After intravenous injection, MREVs are phagocytized by the Kupffer cells of the liver and the macrophages of the spleen. The biodistribution and clearance of MREVs were studied to evaluate their potential for clinical use, MREVs carrying iodine-125-iotrolan were administered intravenously to 12 rats at doses of 400 mg lipid (containing 400 mg iodine) per kilogram body weight. Pairs of rats were anesthetized and scanned at 3 hours, and 1, 7, 14, 27 and 48 days; CT attenuation values of liver, spleen, blood, kidneys and bladder were measured. Immediately following CT, the rats were killed and tissue specimens were radioassayed. Maximum iodine content in liver and spleen was reached at one day and sustained at high levels for seven days. Biologic removal half-time of the agent in both the liver and spleen was six days. Maximum CT enhancements over baseline were observed at 24 hours and reached 210 delta HU in the liver and 880 delta HU in the spleen per gram iodine injected per kilogram body weight. It is concluded that MREVs have appropriate imaging characteristics, biodistribution, and clearance to be effective CT contrast agents.
White
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Department of Radiology, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Slifkin
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Seltzer
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Blau
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Adzamli
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Adams
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D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D014283:Triiodobenzoic Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics
D003287:Contrast Media; D008081:Liposomes; D014283:Triiodobenzoic Acids; C033300:iotrolan