Characterization of a Novel Hafnium-Based X-ray Contrast Agent.
Characterization of BAY-576, a new x-ray contrast agent which is not based on iodine, but rather on the heavy metal hafnium. Compared with iodine, hafnium provides better x-ray absorption in the energy range of computed tomography (CT) and allows images of comparable quality to be acquired at a significantly reduced radiation dose.



A range of standard methods were used to explore the physicochemistry of BAY-576 as well as its tolerability in in vitro assays, its pharmacokinetics and toxicology in rats, and its performance in CT imaging in rabbits.



BAY-576 is an extraordinarily stable chelate with a metal content of 42% (wt/wt) and with excellent water solubility. Formulations of 300 mg Hf/mL exhibited viscosity (3.3-3.6 mPa) and osmolality (860-985 mOsm/kg) in the range of nonionic x-ray agents. No relevant effects on erythrocytes, the coagulation, or complement system or on a panel of 87 potential biological targets were observed. The compound did not bind to plasma proteins of a number of species investigated. After intravenous injection in rats, it was excreted fast and mainly via the kidneys. Its pharmacokinetics was comparable to known extracellular contrast agents. A dose of 6000 mg Hf/kg, approximately 10 to 20 times the expected diagnostic dose, was well tolerated by rats with only moderate adverse effects. Computed tomography imaging in rabbits bearing a tumor in the liver demonstrated excellent image quality when compared with iopromide at the same contrast agent dose in angiography during the arterial phase. At 70% of the radiation dose, BAY-576 provided a contrast-to-noise ratio of the tumor, which was equivalent to iopromide at 100% radiation dose.



The profile of BAY-576 indicates its potential as the first compound in a new class of noniodine x-ray contrast agents, which can contribute to the reduction of the radiation burden in contrast-enhanced CT imaging.
From the *Bayer Pharma AG, Drug Discovery, Berlin, Wuppertal; and †University of Saarland, Inorganic Chemistry, Saarbrücken, Germany.
Thomas
T
Frenzel
Marcus
M
Bauser
Markus
M
Berger
Christoph Stephan
CS
Hilger
Christa
C
Hegele-Hartung
Gregor
G
Jost
Christian
C
Neis
Kaspar
K
Hegetschweiler
Björn
B
Riefke
Detlev
D
Suelzle
Hubertus
H
Pietsch
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics* / Q000633:toxicity; D004195:Disease Models, Animal; D006195:Hafnium / Q000493:pharmacokinetics* / Q000633:toxicity; D008099:Liver / Q000000981:diagnostic imaging; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging*; D019047:Phantoms, Imaging; D011817:Rabbits; D011856:Radiographic Image Enhancement / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D014057:Tomography, X-Ray Computed / Q000379:methods*
D003287:Contrast Media; D006195:Hafnium