Detailed Toxicity Studies of Liposomal Gadolinium-DTPA.
FRITZ, THOMAS MSc *; UNGER, EVAN MD *; WILSON-SANDERS, SUSAN DVM, MS +; AHKONG, QUET FAH PHD ++; TILCOCK, COLIN PHD ++
[Article]
Investigative Radiology.
26(11):960-968, November 1991.
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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 < .05). Nonliposomal Gd-DTPA caused mild cardiomegaly and altered liver enzymes (P < .05). Blank liposomes caused relatively mild splenomegaly (P < .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.
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