Nanomaterials for Medical Imaging …
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are efficient enough to be used as a CT contrast compared to conventional iodine
conjugated nanoparticles [62]. GNPs with sizes in the range of 25 nm are retained in
the vasculature providing excellent contrast for vessel imaging. GNPs with different
sizes were also studied to use as blood pool contrast agents for pre-clinical imaging.
But the study suggested by Ross et al. in 2014 suggested that X-ray attenuation of
gold linearly varies with the concentration of gold chloride and independent of gold
particles [63]. In 2007, Kattumuri et al. used biocompatible surfactant called gumarabic onto GNPs to understand in vivo pharmacokinetics and potential contrast
compared to Iodine in clinical CT. Later in 2010, more detailed experiments in
juvenile swine were performed by the same group to determine the changes in CT
Hounsfield units (HU) about the uptake concentration in pre and post-injection scans
at different X-ray levels. The results revealed that the uptake is high spleen compared
to the liver. At different X-ray voltages, the uptake of GNPs is consistently high at 80
kVp (22 HU) and 140 kVp (27 HU), respectively [64]. Cormode groups have studied
the effect of GNP size from 4 to 152 nm coated with m-PEG in clinical and preclinical CT systems. Results indicated that GNP size of less than 15 nm had shown
more extended circulation compared to larger particles. While the concentration of
GNPs in ex vivo and in vivo determined using ICP OES analysis demonstrated that
larger size particles rapidly accumulate in the liver and spleen [16].
6.2 Surfactant Functionalized GNPs for CT Imaging
Most research works developed GNPs using citrate as reducing agents (Turkevich
method), but the toxicity of the citrate molecules in vivo showed enhanced toxicity.
Researchers found that usage of the surfactants may eradicate the issues related to
the toxicity in vivo. Surfactant polyethylene glycol (PEG) with a methoxy group was
found biocompatible and stable in a biological environment. PEG enabled GNPs to
enhance the contrast characteristics when exposed to X-rays. A first attempt in 2007
by Kim et al. about the capping of PEG after the synthesis of GNPs via chemical
method [65]. The average GNPs size was around 30 nm, showed 5.7 times higher
contrast with circulation time of 4 h compared to Ultravist (commercially available
iodine contrast) having less than 10 min. GNPs based imaging can delineate the
hepatoma region in rats exhibited twofold contrast compared to normal healthy cells
with less toxicity.
Further, less sized GNPs with an average size of 2 and 8 nm were evaluated
the changes in the contrast and behavior of the particles [66, 67]. In 2011, Zhang
et al. studied the complete in vivo toxicity of nanoparticles coated with surfactant
PEG [68]. Results concluded that the toxicity of the GNPs could not be determined
based on the particle size. The influence of the 10 and 60 nm toxicity is relatively
higher compared to the lesser sized GNPs like 5 and 30 nm due to the increased
metabolic rate in the liver. In vivo analysis of 5 and 10 nm are loaded in the liver
and 30 nm collected in the spleen. While 60 nm GNPs revealed the reduction of
white blood cells and increased the transamination levels of alanine and aspartate.
347
are efficient enough to be used as a CT contrast compared to conventional iodine
conjugated nanoparticles [62]. GNPs with sizes in the range of 25 nm are retained in
the vasculature providing excellent contrast for vessel imaging. GNPs with different
sizes were also studied to use as blood pool contrast agents for pre-clinical imaging.
But the study suggested by Ross et al. in 2014 suggested that X-ray attenuation of
gold linearly varies with the concentration of gold chloride and independent of gold
particles [63]. In 2007, Kattumuri et al. used biocompatible surfactant called gumarabic onto GNPs to understand in vivo pharmacokinetics and potential contrast
compared to Iodine in clinical CT. Later in 2010, more detailed experiments in
juvenile swine were performed by the same group to determine the changes in CT
Hounsfield units (HU) about the uptake concentration in pre and post-injection scans
at different X-ray levels. The results revealed that the uptake is high spleen compared
to the liver. At different X-ray voltages, the uptake of GNPs is consistently high at 80
kVp (22 HU) and 140 kVp (27 HU), respectively [64]. Cormode groups have studied
the effect of GNP size from 4 to 152 nm coated with m-PEG in clinical and preclinical CT systems. Results indicated that GNP size of less than 15 nm had shown
more extended circulation compared to larger particles. While the concentration of
GNPs in ex vivo and in vivo determined using ICP OES analysis demonstrated that
larger size particles rapidly accumulate in the liver and spleen [16].
6.2 Surfactant Functionalized GNPs for CT Imaging
Most research works developed GNPs using citrate as reducing agents (Turkevich
method), but the toxicity of the citrate molecules in vivo showed enhanced toxicity.
Researchers found that usage of the surfactants may eradicate the issues related to
the toxicity in vivo. Surfactant polyethylene glycol (PEG) with a methoxy group was
found biocompatible and stable in a biological environment. PEG enabled GNPs to
enhance the contrast characteristics when exposed to X-rays. A first attempt in 2007
by Kim et al. about the capping of PEG after the synthesis of GNPs via chemical
method [65]. The average GNPs size was around 30 nm, showed 5.7 times higher
contrast with circulation time of 4 h compared to Ultravist (commercially available
iodine contrast) having less than 10 min. GNPs based imaging can delineate the
hepatoma region in rats exhibited twofold contrast compared to normal healthy cells
with less toxicity.
Further, less sized GNPs with an average size of 2 and 8 nm were evaluated
the changes in the contrast and behavior of the particles [66, 67]. In 2011, Zhang
et al. studied the complete in vivo toxicity of nanoparticles coated with surfactant
PEG [68]. Results concluded that the toxicity of the GNPs could not be determined
based on the particle size. The influence of the 10 and 60 nm toxicity is relatively
higher compared to the lesser sized GNPs like 5 and 30 nm due to the increased
metabolic rate in the liver. In vivo analysis of 5 and 10 nm are loaded in the liver
and 30 nm collected in the spleen. While 60 nm GNPs revealed the reduction of
white blood cells and increased the transamination levels of alanine and aspartate.