Synthesis, characterization, and computed tomography imaging of a tantalum oxide nanoparticle imaging agent

Abstract

Water-soluble ≤6 nm tantalum oxide nanoparticles have been synthesized and characterized in solution using HPLC-ICP, DLS, and multinuclear NMR. Nanoparticle formulation permitted intravenous injection, in vivo imaging, and subsequent renal clearance. A clinical CT scanner provided excellent resolution following agent injection, and distribution to the arterial system was visualized. In vitro CT imaging studies indicated that at equal molar concentration of tantalum and iodine, tantalum produced greater image contrast than iodine across the diagnostic X-ray spectrum with contrast benefit increasing with peak X-ray energy.

CT Image Contrast of High-ZElements: Phantom Imaging Studies and Clinical Implications

“…These important considerations are beyond the scope of tantalum clearly merits further consideration. Results published to date suggest that some tantalum oxide nanoparticles have physicochemical and biological characteristics that make them attractive for use as intravascular CT contrast agents (16,19,21,22). These water-soluble agents can be formulated at concentrations required for CT and radiography and are well tolerated at high doses.…”

“…Therefore, empirical results rigorously obtained with a clinical CT scanner are valuable. Others have reported testing a subset of the elements we evaluated, with varying levels of rigor (9,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)23,24,(26)(27)(28)(29)(30). Examples of shortcomings in literature reports include the following: (a) Too few elements were evaluated (11,(13)(14)(15)(16)(17)(18)(19)(20)23,24,26,27,29); (b) elemental concentrations were unverified and/or uncorrected or were based on molarity rather than mass (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)23,(26)(27)(28)(29); (c) no patient-relevant phantom was used (11,…”

“…To evaluate the effect of even larger subjects and to consider possible x-ray spectrum optimization, we added filters at the x-ray tube output of 0.2-, 0.5-, and 1.0-mm-thick copper. We reconstructed 0.625-mm-thick images by using a "standard" kernel into a 512 3 512-voxel 32-cm field of view, resulting (5,9,(11)(12)(13)(16)(17)(18)(19)(20)23,24,26,28,29); (f) considerations that affect the measured image contrast were unaccounted for and/or uncorrected, such as the solvent in which the tested compound was dissolved (23,28) and elements other than the active element in the compound (11,18,23,26,28); and (g) image contrast (in Hounsfield units) was not explicitly or precisely reported (11,12,17,20,24,26,28,29).…”

In Vivo Differentiation of Complementary Contrast Media at Dual-Energy CT

“…From the candidates with appropriate attenuation properties, bismuth and tungsten were selected for their additional properties of low toxicity compared with other heavy metals (15) and low cost. Other investigators are developing tantalum-based contrast media (14,16) with x-ray attenuation characteristics that are very similar to those of tungsten.…”

“…The exceptions are elements that have a kedge in this range. Because attenuation increases abruptly as energy increases above the k-edge, these elements have relatively increased attenuation at higher energy, resulting in lower attenuation ratios (14). From the candidates with appropriate attenuation properties, bismuth and tungsten were selected for their additional properties of low toxicity compared with other heavy metals (15) and low cost.…”