Chemistry Reference
In-Depth Information
However, the short lifetime of
18
F limits its application in long-term imaging.
153
Sm is another kind of radionuclide that
can be used in SPECT imaging. Because rare earth ions have similar chemical properties,
153
Sm can also label UCNPs
directly by simple mixing. The relatively long half-lifetime of
153
Sm (1.929 day) enables the biodistribution of the labelled
UCNPs to be conveniently analysed by SPECT imaging.
13.5
bIodIStrIbutIon and toxIcIty oF ucnPs
Although UCNPs have been considered as one of the best candidates for
in vivo
luminescent imaging labels, the possible
toxicity of UCNPs needs to be investigated in detail before any clinical application. Some work has been carried out to deter-
mine the toxicity of UCNPs against cells, but there are relatively few examples that have discussed the biodistribution and
the possible bioeffects of UCNPs in animals.
13.5.1
In Vitro
toxicity of ucnPs
mTT (methyl thiazolyl tetrazolium), mTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carbo-xymethoxyphenyl)-2-(4-sulfophenyl)-
2H-tetrazolium, sodium salts), and CCK-8 mitochondrial metabolic activity assays are common techniques to evaluate the
in vitro
cytotoxicity of materials at the cell level. Numerous studies have been reported to test the cytotoxicity of UCNPs
in different cell lines before the imaging applications. In these studies, cells were incubated with UCNPs for a certain
period, and usually more than 75% cells were found to be viable when the concentration of UCNPs was in the range of
0.05 ~ 20000 µg/mL. These results demonstrated that UCNPs have low
in vitro
cytotoxicity and are biocompatible for the
cell imaging.
Recently, Li and co-workers used the half-maximal inhibitory concentration (IC50) value as another parameter to eval-
uate the cytotoxicity of UCNPs [98]. They considered the water-soluble dopamine-modified NaYF
4
:Yb,Tm@Fe
x
o
y
core/
shell nanoparticles in KB cells. After incubation for 24 and 48 hours, IC50 values of the nanoparticles were measured as
approximately 295 and 190 µg/mL, respectively.
13.5.2
In Vivo
toxicity of ucnPs
13.5.2.1 Biodistribution and Excretion of UCnPs
Before the clinical application of UCNPs, pharmacokinetic studies
of UCNPs are necessary to evaluate their safety. Distribution, metabolism, and excretion are the main three parts in pharma-
cokinetics study. Plasma atomic emission spectroscopy (ICP-AES) is the most common technique to analyse the concentra-
tions of UCNPs in different organs. For example, Zhang and co-workers investigated the biodistribution of Sio
2
-coated [57]
and PEI-modified NaYF
4
:Yb,Er/Tm UCNPs [66], utilising the concentration of Y
3+
as the parameter. A dose of 10 mg/kg wt
Sio
2
-coated UCNPs was intravenously injected into a Wistar rat. The concentration of UCNPs was found to be high in the
lung and heart at the initial stage and gradually excreted by urine or faeces until completely cleared from body after 7 days.
The PEI-modified UCNPs first accumulated in the lung. After 24 hours, the nanoparticles concentrated to the spleen, and
after seven days, no UCNPs were detectable in the rats. Liu and co-workers also employed ICP-AES to analyse the biodis-
tribution of UCNPs over a longer period of time [103]. They tracked PAA-UCNPs (35 nm) and PEg-UCNPs (~30 nm) for
90 days. The concentration of PAA-UCNPs in lung dropped significantly after three days, while the concentration remained
at a certain level in all other organs.
Compared to the ICP-AES measurement, UCL imaging provides another route for the investigation of the biodistribution
of UCNPs in animals
in vivo
. Li and coworkers employed NIR to NIR PAA-coated NaYF
4
:Yb,Tm nanoparticles (~10 nm)
for this [48], and the upconversion imaging results showed that most of the PAA-UCNPs were in the liver and the spleen at
initial stages. As time increased, the upconversion signals in the spleen increased, while the signals in the liver decreased
over 24 hours. After seven days, the upconversion signals were significantly reduced both in the liver and spleen. The
ex vivo
upconversion imaging analysis showed that after 14 days, almost no upconversion signal can be found in the liver and spleen,
while obvious signals were observed in the intestine, indicating hepatobiliary excretion. At the 115th day, no upconversion
signal could be found in any organs of the mouse, indicating complete excretion and clearance. These results were also con-
firmed by ICP-AES analysis.
Liu et al. observed upconversion signals from the liver, spleen, lungs, and bones one day after injection with PAA-UCNPs
and PEg-UCNPs [103]. The signals decreased over the following days until no signals could be detected after seven days.
In these reports, Sio
2
-coated, PEI-modified, PAA-coated, and PEg-coated UCNPs have different biodistribution charac-
teristics in small animals after injection. The differences may come from the dosage, size, aggregation, and surface prop-
erties of Ln-UCNPs, as well as the animal type used in the experiments.
