Characterization of a Novel Hafnium-Based X-ray Contrast Agent.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cytotoxicity and physicochemical properties of hafnium oxide nanoparticles.

Nano-sized hafnium oxide (HfO(2)) particles are being considered for applications within the semiconductor industry. However, little is known about their cytotoxicity. The objective of this work was to assess several HfO(2) nanoparticles (NPs) samples for their acute cytotoxicity. Dynamic light scattering analysis of the samples indicated that the average particle size of the HfO(2) in aqueous dispersions was in the submicron range with a fraction of particles having nano-dimensions. The media used in the toxicity assays decreased or increased the average particle size of HfO(2) NPs due to dispersion or agglomeration. Static time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed numerous surface contaminants on the NPs. Only one HfO(2) sample caused moderate cytotoxicity to human cell lines. The inhibitory sample caused a 50% response in the Live/Dead assay with HaCaT skin cells at 2200 mg L(-1); and a 50% response in the mitochondrial toxicity test at 300 mg L(-1). A microbial inhibition assay based on methanogenic activity also revealed that another HFO(2) sample caused moderate inhibition. The difference in toxicity between samples could not be attributed to size. Instead the difference in toxicity was likely due to differences in the contaminants of the HfO(2). The ToF-SIMS analysis indicated unique signatures of Br and P in the sample toxic to human cell lines suggesting a distinct synthesis was used for that sample which may have been accompanied by inhibitory impurities. The results taken as a whole indicate that HfO(2) itself is relatively non-toxic.

In vitro cytotoxicity and hemocompatibility studies of Ti-Nb, Ti-Nb-Zr and Ti-Nb-Hf biomedical shape memory alloys.

The in vitro cytotoxicity and hemocompatibility of the Ti-Nb, Ti-Nb-Zr and Ti-Nb-Hf biomedical shape memory alloys (SMAs) were investigated by cell culture (L-929 fibroblast cell), hemolytic test and platelet adhesion test, with CP Ti as a reference material. The cytotoxicity test indicates that all the Ti-Nb, Ti-Nb-Zr and Ti-Nb-Hf SMAs show over 94% cell viability for different incubation times (2, 4 and 7 days) in comparison with a negative control and CP Ti. The cell morphology observation shows good polygon-like adherent growth and proliferation of L-929 in the extracts of all the test samples and CP Ti. These results suggest excellent cytocompatibility for the Ti-Nb, Ti-Nb-Zr and Ti-Nb-Hf SMAs. The hemolytic test reveals that the hemolysis ratios of the Ti-Nb, Ti-Nb-Zr and Ti-Nb-Hf alloys are far less than 5%, so they cannot give rise to acute hemolysis. The platelet morphology observation shows almost the same adhered platelet morphology and activation ratio for the test samples in comparison with CP Ti, except the Ti-22Nb-6Hf alloy, which shows a lower activation ratio of platelets, indicating excellent blood compatibility. Therefore, it is proposed that the Ti-Nb, Ti-Nb-Zr and Ti-Nb-Hf SMAs will be candidates to replace Ti-Ni for biomedical applications.

[Bactericidal and biologically stable coatings for medical implants and instruments]. / Bakteritsidnye i biologicheski stoikie pokrytiia dlia meditsinskikh implantov i instrumentov.

The experimental research showed the fine-film coating based on hafnium nitride to inhibit the pathogenic microflora and to exert the bactericidal effect by far less versus that of antibiotics; at the same time, the concentration of hafnium ions in the solution is just within the sensitivity limit detectable by the most recent registration methods--it amounts to less than 10(-10) mol/l. Therefore, according to the research results, the use of such coatings based on hafnium nitride is promising in manufacturing the surgical metal implants and medical instruments.