Detailed toxicity studies of liposomal gadolinium-DTPA.
Acute, subacute, and delayed toxicity testing was assessed in mice for liposomal gadolinium-DTPA (Gd-DTPA), blank liposomes, and nonliposomal Gd-DTPA. In the subacute experiments mice were injected intravenously (IV) with 0.3 mmol/kg Gd-DTPA per day for 30 days in the form of either free Gd-DTPA, liposomal Gd-DTPA, or an equivalent amount of lipid in blank liposomes without Gd-DTPA. The interpolated acute LD50 of liposomal and nonliposomal Gd-DTPA, estimated as a means of identifying the approximate level, was similar (LD50 = 5.7 mmol/kg Gd-DTPA). In subacute toxicity testing, prolonged high doses of liposomal Gd-DTPA caused splenomegaly, cardiomegaly, lymphocytopenia and hypergammaglobulinemia (P less than .05). Nonliposomal Gd-DTPA caused mild cardiomegaly and altered liver enzymes (P less than .05). Blank liposomes caused relatively mild splenomegaly (P less than .05) but few other changes. Delayed testing three months after the subacute testing showed that most of the changes caused by the liposomal Gd-DTPA were reversible.
Fritz
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T
Department of Radiology, University of Arizona Health Sciences Center, Tucson 85724.
Unger
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Wilson-Sanders
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Ahkong
Q F
QF
Tilcock
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C
D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced; D003287:Contrast Media / Q000633:toxicity*; D005260:Female; D019786:Gadolinium DTPA; D006529:Hepatomegaly / Q000139:chemically induced; D006942:Hypergammaglobulinemia / Q000139:chemically induced; D007928:Lethal Dose 50; D008081:Liposomes; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D004369:Pentetic Acid / Q000008:administration & dosage / Q000633:toxicity*; D013163:Splenomegaly / Q000139:chemically induced
D003287:Contrast Media; D008081:Liposomes; D009942:Organometallic Compounds; D004369:Pentetic Acid; D019786:Gadolinium DTPA