Commonly Used Nanomaterials in Molecular Imaging

1. Commonly Used Nanomaterials
in Molecular Imaging
CD
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Target
Fluorescence
Imaging
Advantages:
●High sensitivity
●Multicolor imaging
●Activatable
Disadvantages:
●Low spatial resolution
●Poor tissue penetration MRI
Advantages:
●High spatial resolution
●No tissue penetrating limit
Disadvantages:
●Relatively low sensitivity
●High Cost
●Long imaging time
CT Imaging
Advantages:
●High spatial resolution
●No tissue penetrating limit
Disadvantages:
●Radiation risk
●Not quantitative
Ultrasound Imaging
Advantages:
●Real-time
●Low cost
Disadvantages:
●Operator dependent analysis
●Low resolution
PET Imaging
Advantages:
●High sensitivity
●No issue penetrating limit
●Quantitative
●Whole-body scanning
Disadvantages:
●Radiation risk
●High cost
SPECT Imaging
Advantages:
●High sensitivity
●NO tissue penetrating limit
Disadvantages:
●Radiation risk
●Low spatial resolution

2. Nanomaterials (e.g. nanoparticles) display special physical and biological behavior and unique
interactions with biomolecules. They possess large surface area and inherent functionalities, making
structural modifications feasible to change their pharmacokinetics, prolong their vascular circulation
life-time, improve their extravasation capacity, ensure an enhanced biodistribution in vivo and
sustainably control the delivering efficacy for drug cargoes. In addition, nanoparticles conjugated with
specific targeting ligands show a high targeted binding capability to diseased regions.
Nanomaterials have been applied as efficient carriers for targeted drug delivery and therapeutic
agents as well as for gene transportation. Molecular imaging is an attractive and fast-growing
research field, in which several nanomaterials have been used as imaging agents (Table 1). As an
emerging interdisciplinary research field, molecular imaging combines chemistry, biology,
pharmacology, and medicine to monitor in vitro and in vivo biomedical or physiological processes at
molecular and cellular levels, which provides valuable information for treatment strategies for various
diseases.
Table 1: Characteristics of several representative nanomaterials and their biomedical applications.
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Type of
Nanoparticle
Synthetic Protocol Size Range
Possible Surface
Modifications
Imaging Modality
Applicable
Gold
nanoparticle
Biological reduction,
colloidal synthesis, vapor
precipitation
Several to hundreds of
nm
Lipids, polymeric shell,
targeting ligands or
biomolecules
CT, optical imaging
Silica
nanoparticle
Chemical polymerization,
microemulsion, sol-gel
Tens to hundreds of
nm
Charge, polymer, targeting
ligands or biomolecules
MRI, optical imaging
Carbon
nanotube
Arc discharge, laser
ablation, vapor
precipitation
Tens of nm
Polymeric shell, targeting
ligands or biomolecules
MRI, optical,
radionuclide imaging
Quantum dot
Colloidal synthesis, self-
assembly, viral assembly
Several to tens of nm
Lipids, polymer, targeting
ligands or biomolecules
Optical imaging
Iron oxide
Coprecipitation,
decomposition,
microemulsion, sol-gel,
thermal
Several to tens of nm
Charge, dextran, lipids,
polymer, targeting ligands or
biomolecules
MRI
Dendrimer
Organic chemistry
techniques
Several nm varies
from different
“generation”
Charge, polymer, targeting
ligands or biomolecules
MRI, optical imaging
Liposome Emulsion, polymerization
Tens to hundreds of
nm
Charge, polymer, targeting
ligands or biomolecules, viral
protein coating,
MRI, optical,
radionuclide imaging
Microbubble
Emulsion, layer-by-layer
fabrication, polymerization
Tens to thousands of
nm
Polymeric shell, targeting
ligands or biomolecules
Ultrasound imaging
Micelle Microemulsion Tens of nm
Charge, polymer, targeting
ligands or biomolecules
MRI, optical,
radionuclide imaging
Adenovirus Replication in host nucleus
Tens to hundreds of
nm
Charge, polymer, targeting
ligands or biomolecules
MRI, optical imaging

3. ◆ Five aspects need to be considered when developing an imaging agent with nanoparticles:
1) The toxicity of nanoparticles for living subjects and humans;
2) Any possible metabolites after vascular circulation or cell uptake;
3) The biocompatibility and biodegradability to avoid harmful accumulations in organs, tissues, and
blood;
4) The availability for chemical modifications of nanoparticles;
5) The in vitro and in vivo comprehensive assessments of synthesized nanoparticles before practical
applications for living subjects or humans.
◆ The common methodologies for design and functionalization strategies of nanoparticles are
summarized below:
1) Select and fabricate nanoparticles core
Based on imaging purposes and a specific imaging modality, the core of the nanoparticle is selected
and the synthesis method of fabrication of the structure of imaging probes is determined.
2) Synthesize shell structure
Compared with the core of nanoparticles, the shell structure usually possesses more complicated
functions including preventing the core from the external microenvironment and improving the core
stability and physical property.
3) Modify surface
To maintain the nanoparticles' stability, surface coatings with stabilizers or emulsions may be
necessary if the outer interface of the shell is too sensitive when exposed to bio-medium.
• Fluorescence imaging
Fluorescence imaging is one of the major techniques in optical imaging to analyze the propagation of
nonionizing radiation, light photons through a medium such as tissue. It is the visualization of molecular
processes or structures via fluorescent dyes or proteins. Fluorescence imaging can be applied in a wide
range of experiments such as the location and dynamics of gene expression, protein expression, and
molecular interactions in cells and tissues.
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Design and Functionalization of Nanoparticles in Molecular Imaging
Nanomaterials Used in Different Molecular Imaging

4. • MRI
MRI, magnetic resonance imaging, is one of the most widely used and powerful tools for noninvasive
clinical diagnosis. It possesses a high degree of soft-tissue contrast, spatial resolution, and depth of
penetration. There are several advantages of using nanoparticles as imaging probes compared with
conventional imaging agents: 1) the concentration of the imaging agent is controllable in each
nanoparticle during the synthesis process; 2) the tunability of the nanoparticles' surface is beneficial to
target a specific location in the body and prolong the circulation time of the agent in the blood; 3)
nanoparticles can be used as multifunctional molecular imaging agents due to their two or more
properties.
Table 2. Selected examples of nanomaterials used in fluorescence imaging.
Table 3. Selected examples of nanomaterials used in MRI.
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AuNP: gold nanoparticle; QD: quantum dot; UCNP: upconverting nanoparticle.
NP: nanoparticle; USPIO: ultra-small superparamagnetic iron oxide; MNP: magnetic nanoparticle.
NP Type Size (nm) Applications Imaging
Alpha(nu)beta(3)-Gd
(paramagnetic particle)
273 Imaging angiogenesis T1
Liposomal gadolinium 125 Imaging placenta as blood-pool contrast T1
RBC encapsulated iron particles 60 Blood-pool contrast with longer lifetime T1, T2
PEGMnCaP NPs 60 PH-activatable contrast in cancer T1, T2
USPIO-PEI 100 Determining nanoparticle vehicle unpackaging for gene T2
P-selectin-MNP(iron oxide)-PBP 50 Imaging post-stroke neuroinflammation T2
NP Type Imaging Agent Size (nm) Applications
Cy5.5-substrate/AuNP Cy5.5 20 Detecting protease activity
Cy5.5-DEVD-DOPAK/AuNP Cy5.5 37.8
Testing caspase-3 to identify apoptosis
activity in cells
QD710-Cy7-PEGylated lipids Cy7 20
Monitoring NP accumulation and
dissociation kinetics in tumor
QD710-Dendron/RGD (InP/ZnS
core/shell QDs)
Quantum dots 12 Targeted imaging tumor cells
Perylenediimide-containing
polysiloxane core and silica shell
Perylenediimide 18, 70 Detecting nanotoxicity in alive cells
AB3-UCNP(NaYF4:Yb/Tm/Er)-
RB/KE108
UCNP 14
Monitoring cellular uptake of
nanoparticles and combined with therapy

5. • CT imaging
Computed tomography (CT) is an X-ray based, a whole-body imaging technique and is widely used in
medicine. Although iodinated small molecules or barium suspensions are clinically approved contrast
agents for CT, developing nanoparticle-based CT contrast agents have attracted more attention due to
the growing population of renally impaired patients and those who are hypersensitive to iodinated
contrast. Nanoparticle-based CT contrast agents possess several advantages over small molecule ones,
including long blood-pool residence times, and the potential for cell tracking and targeted imaging
applications.
• Ultrasound imaging
Ultrasound (US) imaging is a diagnostic medical procedure that uses high-frequency sound waves to
view inside the body. As real-time captured imaging, ultrasound images can not only show the movement
of the body's internal organs but also present the blood flowing through the blood vessels. This technique
does not require the use of ionizing radiation, nor the injection of nephrotoxic contrast agents. Since there is
a great progress in the discovery of various disease-specific biomarkers and in the development of
nanoparticle fabrication, nanoparticle-based ultrasound contrast agents have made a big development.
Those contrast agents could extravasate through the leaky vasculature of a tumor into the interstitial
space with less echogenic than microbubbles.
Table 4. Selected examples of nanomaterials used in CT imaging.
Table 5. Selected examples of nanomaterials used in ultrasound imaging.
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AuNP: gold nanoparticle.
AuNP: gold nanoparticle.
NP Type Size (nm) Applications Classification
Silica coated NP into perfluorobutane
microbubble
Near 3000
Ultrasound imaging agents with
potential therapeutic applications
Gas
Exosome-like silica NP 30–150 Stem cell imaging agent Solid
Gas-NP 290 PH related contrast agents in tumor Gas
Porphyrin nanodroplet 185 Tumor imaging contrast agent Gas
FA-PEG-CS and perfluorooctyl
bromide nanocore
229.5 Molecular tumor imaging agents Liquid
NP Type Size (nm) Applications
PSMA-specific aptamer
conjugated AuNP
29.4 Imaging prostate cancer cells
Liposomal iodine 400 Imaging macrophage-rich atherosclerotic plaques
Tantalum oxide <6 Producing greater imaging capability than iodine
AuNP 20 Incorporating RBC to image blood flow
AuNP 27–176 AuNP with CT contrast capability

6. • PET/SPECT imaging
As a powerful and widely used nuclear medicine technology, PET (positron emission tomography)
possesses high tissue penetration and high sensitivity and is ideal for real-time quantitative imaging
analysis. Similar to PET, SPECT (single-photon emission computed tomography) is also widely used nuclear
medicine technology which can detect abnormal biochemical function before changes in anatomy. Both
of them are suffered from high costs and radioactive exposure. Nanoparticles in PET/SPECT are generally
used for tumor detection. Tumor imaging can occur through specific binding to receptors or via the EPR
effect as well as being acquired through active and passive accumulation in target lesions.
Each imaging modality has its own unique strengths. Multimodality imaging, combining two or more
imaging modalities, can provide more comprehensive structural, functional and molecular information,
which offers the prospect of improved diagnostics and therapeutic monitoring abilities. Nanoparticles have
been used for the development of dual-modal or multimodal probes at an incredibly fast rate. For
example, as dual-modal imaging probes, nanoparticles administrate a single contrast agent for different
types of imaging modalities and possess signal consistency at the target region.
Creative Diagnostics has presented a summary of commonly used nanomaterials in molecular imaging. If
you desire any raw materials mentioned above, please visit our website to see more.
Table 6. Selected examples of nanomaterials used in PET/SPECT imaging.
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MSN: mesoporous silica nanoparticle; TNP: tri-reporter nanoparticle; AuNP: gold nanoparticle.
NP Type Size (nm) Applications Imaging Modality
18
F-labeled DBCO-PEGylated MSN 100–150 Imaging tumor PET
64
Cu labeled CANF-comb
nanoparticle
16–22
Imaging natriuretic peptide clearance
receptor in prostate cancer
PET
64
Cu-TNP 20
Imaging macrophages in
inflammatory atherosclerosis
PET
125
I silver nanoparticle 12 Monitoring distribution of nanoparticles SPECT
125
I labeled cRGD-PEG-AuNP 31
Detecting cancer cells and imaging
tumor sites
SPECT

7. References:
1. Polyak, A., & Ross, T. L. (2018). Nanoparticles for SPECT and PET imaging: towards personalized
medicine and theranostics. Current medicinal chemistry, 25(34), 4328-4353.
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nanoparticles for bioimaging. Nanomedicine, 14(13), 1759-1769.
3. Cormode, D. P., Naha, P. C., & Fayad, Z. A. (2014). Nanoparticle contrast agents for computed
tomography: a focus on micelles. Contrast media & molecular imaging, 9(1), 37-52.
4. Mallidi, S., Wang, B., Mehrmohammadi, M., Qu, M., Chen, Y. S., Joshi, P., ... & Sokolov, K. (2009,
September). Ultrasound-based imaging of nanoparticles: From molecular and cellular imaging to
therapy guidance. In 2009 IEEE International Ultrasonics Symposium (pp. 27-36). IEEE.
5. Lee, D. E., Koo, H., Sun, I. C., Ryu, J. H., Kim, K., & Kwon, I. C. (2012). Multifunctional nanoparticles for
multimodal imaging and theragnosis. Chemical Society Reviews, 41(7), 2656-2672.
6. Estelrich, J., Sánchez-Martín, M. J., & Busquets, M. A. (2015). Nanoparticles in magnetic resonance
imaging: from simple to dual contrast agents. International journal of nanomedicine, 10, 1727.
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Nanoscale, 11(3), 799-819.
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