Detection and Description of Tissue Disease: Advances in the Use of Nanomedicine for Medical Imaging - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 249

longer than is seen with conventional tracers which have blood half-
lives of <5 min. This agent was used to measure the plasma volume
and endothelial permeability of subcutaneous xenograft breast
cancer xenograft tumors [17].

8.2.2 Other Radioopaque Elements

In addition to iodine, a number of other elements have desirable
characteristics for CT contrast agents and are being developed for
use. For example, in work by Rabin et al . [18], nanocrystals of Bi 2 S 3
were coated with the polymer polyvinylpyrrolidone (PVP). (The
uncoated crystals could not be used as imaging agents because of
aggregation and rapid clearance.) When these nanoparticles were
tested in vivo , sufficient increases in contrast were achieved for clear
imaging of vascular structures. The blood half-life was 140 ± 15 min,
which is significantly longer than that of commercial iodinated agents
(typically <10 min). At later time points, the enhancement of tissues
involved in the RES was observed, leading to the suggestion that the
agent could be used to image the liver and detect tumor metastases
in that organ. The toxicity of these nanoparticles was tested in vivo
and found to be much lower than the free bismuth ions (LD 50' s
of 8 mM and 100 mM for bismuth ions and Bi 2 S 3 nanoparticles,
respectively).
Gold nanoparticles (AuNPs) also have potential application in
this field, with gold's higher atomic number (79) than iodine (53)
resulting in greater attenuation of x-rays. As with bismuth particles,
AuNPs have to be coated, for example with gum Arabic, to reduce
their hematological and renal toxicity [19]. They have been shown to
be stable in vivo and to produce good contrast in CT applications [19,
20]. Another advantage of AuNPs is that they have a large surface-
area-to-volume ratio, providing more opportunity for surface
modification. For example, Aydogan et al . reported the modification
of AuNPs with a structural analogue of glucose, 2-deoxy-D-glucose
(2DG) [21]. This modification increased their uptake by tumor cells
in vitro by a factor of 4 compared with unmodified AuNPs, although
the exact mechanism of uptake has yet to be fully defined. In another
example, targeting was achieved by entrapping AuNPs in dendrimers,
then targeting the combined nanoparticle using folate attached to
the outside of the dendrimer, resulting in improved binding to KB
cells (human epithelial carcinoma cells) in vitro [22].