was implemented. The study demonstrated the linear correlation between the activity
of radionuclides and the intensity of CL and also showed that the diagnostic dose of
18 F-FDG is feasible for detecting nodal disease by CLI.
Cerenkov-Induced Therapy The applications of CL have also been rapidly
expanding to cancer therapy. Photodynamic therapy (PDT) utilizes photosensitizers,
which absorb light and produce reactive oxygen species (ROS) to kill cancerous
cells. Conventional PDT uses red-to-infrared light from external light sources to
excite the photosensitizers. Because the tissue permeability of light is poor, the light
source needs to be delivered to the deep tumor site by insertion of fiber optics into the
patient’s body. This invasive approach could be avoided by CL-induced PDT.
Photosensitizers in proximity to clinically relevant radionuclides may be excitable
by CL, resulting in localized cytotoxic ROS generation. It was demonstrated that CL
generated by
90 Y excites porphyrin, a photosensitizer, and inhibits cell growth
[79]. Furthermore, nanoparticles have shown some promising results as a part of
CL-based PDT strategies. For example, it was demonstrated that titanium dioxide
could be excited by CL and generate ROS from water and oxygen molecules.
Further, titanium dioxide in the presence of
18 F-FDG or
64 Cu could induce PDT
in vivo [80]. In addition to titanium dioxide, some other nanoparticles have also been
reported to induce PDT such as chlorin e6 nanoparticles and copper sulfide
nanoparticles [81, 82].
Summary Cerenkov luminescence has garnered great attention in both science and
medicine since the first biomedical application of CL was reported in 2009. CL
provides an easy-to-prepare and cost-effective imaging modality. Because CL is
generated by most PET imaging radiotracers, multimodal imaging with both CLI
and PET may be possible. CL combined with small molecules, biomolecules, and
nanoparticles has been studied to improve in vivo radiotracer tracking capabilities.
Further, a new targeted therapeutic paradigm that selectively kills only cells in
proximity to CL-generating radiotracers may be accomplished with CL. CL-induced
PDT may provide a less invasive approach compared to the conventional PDT in the
clinic. However, there are some limitations that must be overcome, such as the weak
intensity of CL and prolonged exposure to high dose of radionuclides. Therefore,
further development of this field is needed before clinical relevance can be achieved.
Compliance with Ethical Standards
Conflict of Interest: Evan P. Stater declares that he has no conflict of interest. Magdalena Skubal
declares that she has no conflict of interest. Ryo Tamura declares that he has no conflict of interest.
Jan Grimm declares that he has no conflict of interest.
Ethical Approval: This chapter does not contain any studies with human participants or animals
performed by any of the authors.
Funding: Not applicable.
Informed Consent: Informed consent was obtained from all individual participants included in
referenced studies.
218
E. P. Stater et al.
of radionuclides and the intensity of CL and also showed that the diagnostic dose of
18 F-FDG is feasible for detecting nodal disease by CLI.
Cerenkov-Induced Therapy The applications of CL have also been rapidly
expanding to cancer therapy. Photodynamic therapy (PDT) utilizes photosensitizers,
which absorb light and produce reactive oxygen species (ROS) to kill cancerous
cells. Conventional PDT uses red-to-infrared light from external light sources to
excite the photosensitizers. Because the tissue permeability of light is poor, the light
source needs to be delivered to the deep tumor site by insertion of fiber optics into the
patient’s body. This invasive approach could be avoided by CL-induced PDT.
Photosensitizers in proximity to clinically relevant radionuclides may be excitable
by CL, resulting in localized cytotoxic ROS generation. It was demonstrated that CL
generated by
90 Y excites porphyrin, a photosensitizer, and inhibits cell growth
[79]. Furthermore, nanoparticles have shown some promising results as a part of
CL-based PDT strategies. For example, it was demonstrated that titanium dioxide
could be excited by CL and generate ROS from water and oxygen molecules.
Further, titanium dioxide in the presence of
18 F-FDG or
64 Cu could induce PDT
in vivo [80]. In addition to titanium dioxide, some other nanoparticles have also been
reported to induce PDT such as chlorin e6 nanoparticles and copper sulfide
nanoparticles [81, 82].
Summary Cerenkov luminescence has garnered great attention in both science and
medicine since the first biomedical application of CL was reported in 2009. CL
provides an easy-to-prepare and cost-effective imaging modality. Because CL is
generated by most PET imaging radiotracers, multimodal imaging with both CLI
and PET may be possible. CL combined with small molecules, biomolecules, and
nanoparticles has been studied to improve in vivo radiotracer tracking capabilities.
Further, a new targeted therapeutic paradigm that selectively kills only cells in
proximity to CL-generating radiotracers may be accomplished with CL. CL-induced
PDT may provide a less invasive approach compared to the conventional PDT in the
clinic. However, there are some limitations that must be overcome, such as the weak
intensity of CL and prolonged exposure to high dose of radionuclides. Therefore,
further development of this field is needed before clinical relevance can be achieved.
Compliance with Ethical Standards
Conflict of Interest: Evan P. Stater declares that he has no conflict of interest. Magdalena Skubal
declares that she has no conflict of interest. Ryo Tamura declares that he has no conflict of interest.
Jan Grimm declares that he has no conflict of interest.
Ethical Approval: This chapter does not contain any studies with human participants or animals
performed by any of the authors.
Funding: Not applicable.
Informed Consent: Informed consent was obtained from all individual participants included in
referenced studies.
218
E. P. Stater et al.