Preclinical acute toxicology study of surfactant-stabilized ultrasound contrast agents in adult rats.
Gas-filled microbubbles are used as contrast agents in diagnostic ultrasound imaging. A preclinical, acute toxicity study of 2 surfactant-stabilized ultrasound contrast agents (ST68 and ST44) was conducted. Subjects were 104 Sprague-Dawley rats (experimental doses, 0.1, 0.2, 0.8, and 1.0 mL/kg; control, 1.0 mL/kg saline) that were studied for 14 days after contrast; clinical signs, weight, blood, and urine were evaluated. Histopathology was performed following euthanasia. Of the 40 animals receiving ST44, 4 died prematurely and a dose dependency was demonstrated (P = .011), whereas in the ST68 groups only 1 death occurred (no dose dependency; P = .48). Only the weight of rats injected with ST44 varied significantly (P = .0003). This dependency was also found for 3 of 5 urine parameters and 4 of 36 blood parameters (P < .05). For ST68, only 1 urine parameter showed significance (P < .0001). Giant cell infiltration in the lungs was significantly higher than controls in the ST44 0.1 mL/kg and the ST68 0.8-1.0 mL/kg groups (P < .01). It is concluded that the prudent choice for future nonrodent, toxicology studies and potentially for human clinical trials is ST68 (given the deaths in the ST44 groups).
Forsberg
Flemming
F
Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA. flemming.forsberg@jefferson.edu
Liu
Ji-Bin
JB
Patel
Mihir
M
Liu
Liping
L
Lin
Ling
L
Solis
Carl
C
Fox
Traci B
TB
Wheatley
Margaret A
MA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003287:Contrast Media / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006601:Hexoses / Q000633:toxicity*; D008136:Longevity / Q000187:drug effects; D008297:Male; D045423:Microbubbles; D011136:Polysorbates / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000633:toxicity; D023382:Toxicity Tests, Acute; D014463:Ultrasonography
D003287:Contrast Media; D006601:Hexoses; D011136:Polysorbates; C418026:ST68; D013501:Surface-Active Agents