Preparation, characterization, and evaluation of ioxilan carbonate particles for computed tomography contrast enhancement of liver.
OBJECTIVE
To prepare and characterize a new particulate contrast medium, cyclic carbonate of ioxilan (IX-C) particles, as a macrophage imaging agent for computed tomography (CT) enhancement of the liver.


METHODS
Cyclic carbonate of ioxilan was synthesized from ioxilan, a nonionic water-soluble contrast agent. The IX-C particles prepared by a solvent extraction-evaporation method were characterized by size distribution, degradability, suspension stability, and median lethal dose. Pharmacokinetics of IX-C particles and their effectiveness in enhancing liver attenuation and in detecting hepatic tumors were evaluated using normal and VX2-tumor-bearing rabbits.


RESULTS
The IX-C particles were biodegradable, with ioxilan and carbon dioxide as the degradation products. The particles had an average size of 1 to 2 microns and were stable in saline suspension. The median lethal dose determined for IX-C particles was 2.6 and 3.1 g/kg body weight for female and male rabbits, respectively. A dose of 200 mg iodine/kg body weight caused an increase of 38 Hounsfield units in liver attenuation. In rabbit, hepatic clearance of the contrast medium occurred in 2 days. A tumor barely visible in precontrast scans could be detected after contrast injection.


CONCLUSIONS
Development of particulate contrast medium from nonionic contrast agents represents a new approach. Ioxilan carbonate particles have suitable physicochemical properties that warrant further studies before clinical evaluation.
Li
C
C
Division of Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Kan
Z
Z
Yang
D J
DJ
Kuang
L R
LR
Liu
C W
CW
Wright
K C
KC
Wallace
S
S
D000818:Animals; D001673:Biodegradation, Environmental; D002254:Carbonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D005260:Female; D006868:Hydrolysis; D007089:Image Enhancement; D007472:Iohexol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D008099:Liver / Q000000981:diagnostic imaging*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D011817:Rabbits; D014057:Tomography, X-Ray Computed
D002254:Carbonates; D003287:Contrast Media; D007472:Iohexol; C055357:ioxilan