Radio-labeled Nanoparticles for Biomedical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 195

dendrimers can be used for both passive targeting, where their size is coupled with the
leaky vasculature of the tumor, direct accumulation, and active targeting, where the
surface is functionalized with a moiety that recognizes a cell surface receptor.
poly(amido)amine (pAmAm), one of the most commonly utilized dendrimers,
has been functionalized with targeting groups for in vivo and in vitro applications.
Zhang et al . have conjugated folic acid to pAmAm generation 5 (g5) dendrimers and
radiolabeled them with 99m Tc via DTpA chelation. The pAmAm dendrimers were
partially acetylated to improve their solubility and increase cellular uptake specificity.
The dendrimer conjugate, 99m Tc-pAmAm-fA, was studied in Kb tumor-bearing
mice. In vitro stability studies in phosphate-buffered saline and newborn calf serum at
37°C showed that 90% and 78%, respectively, of the dendrimer was retained after 6 h.
In vivo studies showed that the 99m Tc-pAmAm-fA conjugate had more than 70%
stability in the blood. In vivo biodistribution of the 99m Tc-pAmAm-fA conjugate in
Kb-bearing mice at 2, 4, and 6 h p.i. showed an expected increase in accumulation of
the radiolabeled conjugate at the tumor (13.34 ± 1.36% ID/g, 6 h p.i.). Kidney
accumulation was influenced by the presence of folate-binding proteins that regulate
uptake. Some accumulation was also observed in the liver (9.48 ± 0.51% ID/g) and
heart (6.88 ± 0.47% ID/g). microSpeCT images taken between 2 and 6 h p.i. confirm
the increased accumulation of 99m Tc-pAmAm-fA at the tumor and kidney. In a
subsequent study, tumor uptake was increased by spacing the pAmAm dendrimer
with a peg linker, which allowed for greater structurally flexibility and selective
binding of folic acid to the metastatic tumor while mostly evading the mononuclear
phagocyte system (mpS) [67, 69]. These studies show that folic acid-conjugated
dendrimers have great promise for diagnostic imaging in cancer. In a similar study,
acetylated pAmAm was labeled with 99m Tc and conjugated to either biotin or
avidin. The nanoconjugates were evaluated in vitro in HeLa cells, and their biodis-
tribution quantified in normal healthy mice. A relatively fast blood clearance to
tissues and excretory organs was observed for the radiolabeled dendrimer conju-
gates. Unlike the 99m Tc-pAmAm-fA, high uptake in the ReS organs (liver and
spleen) was observed in the microSpeCT mice images. This could be due to non-
specific interactions between the hepatic cells and the net positive charge on the
dendrimers, the relatively larger size of the resultant pAmAm-avidin molecule,
or the interaction between the receptors on the hepatocytes and mannose residues
on the avidin molecule [68].

7.3.5 Radiolabeled carbon-based Nanostructures for spect imaging

Carbon-based nanostructures are made of cylindrical graphite sheets rolled at specific
and discrete angles, often less than 100 nm in size. The graphite sheet, or graphene,
can be rolled as either single- or multiwalled nanotubes (SWNT or mWNT). These
carbon nanotubes (CNTs) are either metallic or semiconductive, possessing thermal
and electrical properties. They have been utilized in nanotechnology, electronics, and
optics as biosensors. They are also being investigated as drug delivery vehicles, diag-
nostic biosensors, and thermal ablative agents, as modifications of the tubes allow for
these applications [70]. CNTs can be functionalized to improve their solubility, lower