imaging as well as cancer imaging and therapy. Cerenkov luminescence imaging
(CLI) is a new medical imaging modality that captures CL emitted from clinically
relevant radionuclides via optical imaging instruments and allows multimodal imaging in combination with positron emission tomography (PET) imaging. Further, CL
has been applied with nanomaterials, small molecules, and biomolecules for better
imaging and therapy in cancer research. This section covers the basics of CL and the
recent advances of CLI for diagnosis of disease as well as its applications to cancer
therapies.
In 1934, the Russian scientist Pavel Alekseyevich Cerenkov observed faint blue
light when he accidentally placed a sulfuric acid solution over radium salts [62]. He
concluded the observed visible light was produced by charged subatomic particles
traveling faster than the phase velocity of light in a dielectric medium [63]. Further
theoretical studies were conducted by Ilya Frank and Igor Tamm, who described the
significance of particle energy, cone angle of emitted light, and refractive index of
media. In 1958, Cerenkov, Frank, and Tamm were awarded the Nobel Prize in
Physics for their discovery and explanation of the Cerenkov effect.
Positrons and electrons, collectively referred to as charged beta (β) particles, are
produced by radioactive decay. In dielectric media (mainly tissue/water in biomedical contexts), β particles are traveling faster than the phase velocity of light. Charged
β particles with high energy interact with surrounding water and polarize the
randomly oriented water molecules. The polarized water molecules then relax to
the ground state by emitting photons in the direction of the charged particle travel,
creating a coherent wavefront [61]. The photons propagate at a forward angle (θ)
from the direction of the charged particle vector.
Cerenkov Luminescence Imaging The Cerenkov phenomenon has been applied
in the fields of physics and engineering in a variety of applications, such as in
detectors for particle physics and nuclear power plants [64]. In 2009, the first
biomedical imaging application of the Cerenkov phenomenon was reported by
Robertson et al. who described Cerenkov luminescence imaging (CLI), using
18 Ffluorodeoxyglucose (
18 F-FDG) in vivo imaged with widely used optical instrumentation for bioluminescence imaging, which provides the necessary sensitivity [60].
This study set the foundation of CLI, and biomedical applications of CLI have been
rapidly expanding ever since. CLI provides a quantitative multimodal imaging
system in conjunction with positron emission tomography (PET) and could be
advantageous over the conventional imaging modalities in the clinic in terms of
cost, time, and applicability of radionuclides (Fig. 3a, b). Some preclinical studies
for CLI have been reported using clinically relevant radionuclides including
18 F,
89 Zr,
90 Y,
68 Ga, and
225 Ac [65, 67].
CLI for experimental imaging in small animals utilizes a bioluminescence imaging system equipped with a charged coupled device (CCD) camera in a chamber to
exclude ambient light [68].
18 F-FDG, a radiotracer for glycolytic metabolism, is one
of the most common radiotracers for PET imaging because it preferentially accumulates in cancer cells [69]. CL from
18 F-FDG has been shown to strongly correlate
with signal intensity in PET imaging [70]. In addition to small-molecule
The Present and Future of Optical Imaging Technologies in the Clinic:. . .
215
(CLI) is a new medical imaging modality that captures CL emitted from clinically
relevant radionuclides via optical imaging instruments and allows multimodal imaging in combination with positron emission tomography (PET) imaging. Further, CL
has been applied with nanomaterials, small molecules, and biomolecules for better
imaging and therapy in cancer research. This section covers the basics of CL and the
recent advances of CLI for diagnosis of disease as well as its applications to cancer
therapies.
In 1934, the Russian scientist Pavel Alekseyevich Cerenkov observed faint blue
light when he accidentally placed a sulfuric acid solution over radium salts [62]. He
concluded the observed visible light was produced by charged subatomic particles
traveling faster than the phase velocity of light in a dielectric medium [63]. Further
theoretical studies were conducted by Ilya Frank and Igor Tamm, who described the
significance of particle energy, cone angle of emitted light, and refractive index of
media. In 1958, Cerenkov, Frank, and Tamm were awarded the Nobel Prize in
Physics for their discovery and explanation of the Cerenkov effect.
Positrons and electrons, collectively referred to as charged beta (β) particles, are
produced by radioactive decay. In dielectric media (mainly tissue/water in biomedical contexts), β particles are traveling faster than the phase velocity of light. Charged
β particles with high energy interact with surrounding water and polarize the
randomly oriented water molecules. The polarized water molecules then relax to
the ground state by emitting photons in the direction of the charged particle travel,
creating a coherent wavefront [61]. The photons propagate at a forward angle (θ)
from the direction of the charged particle vector.
Cerenkov Luminescence Imaging The Cerenkov phenomenon has been applied
in the fields of physics and engineering in a variety of applications, such as in
detectors for particle physics and nuclear power plants [64]. In 2009, the first
biomedical imaging application of the Cerenkov phenomenon was reported by
Robertson et al. who described Cerenkov luminescence imaging (CLI), using
18 Ffluorodeoxyglucose (
18 F-FDG) in vivo imaged with widely used optical instrumentation for bioluminescence imaging, which provides the necessary sensitivity [60].
This study set the foundation of CLI, and biomedical applications of CLI have been
rapidly expanding ever since. CLI provides a quantitative multimodal imaging
system in conjunction with positron emission tomography (PET) and could be
advantageous over the conventional imaging modalities in the clinic in terms of
cost, time, and applicability of radionuclides (Fig. 3a, b). Some preclinical studies
for CLI have been reported using clinically relevant radionuclides including
18 F,
89 Zr,
90 Y,
68 Ga, and
225 Ac [65, 67].
CLI for experimental imaging in small animals utilizes a bioluminescence imaging system equipped with a charged coupled device (CCD) camera in a chamber to
exclude ambient light [68].
18 F-FDG, a radiotracer for glycolytic metabolism, is one
of the most common radiotracers for PET imaging because it preferentially accumulates in cancer cells [69]. CL from
18 F-FDG has been shown to strongly correlate
with signal intensity in PET imaging [70]. In addition to small-molecule
The Present and Future of Optical Imaging Technologies in the Clinic:. . .
215