5.2 Metal-Based Therapeutic Agents
Metallodrugs are designed to induce pharmacological effects by interacting with
proteins (in particular with catalytically active enzymes) or directly with DNA
[35]. Because of their unique properties, metallodrugs are the subject of intense
research efforts. Platinum-based complexes are examples of the most widely used
anticancer agents. Currently researched compounds are mainly based on platinum
but also other metals such as ruthenium, titanium, gallium, or silver are under
investigation. Until now, no imaging technique was available to visualize the
distribution of these drugs in living subjects. Because metals such as platinum
emit energetic characteristic X-rays, they are highly amenable to imaging via
XFCT [18]. XFCT will play a pivotal role in the biological characterization and
optimization of metal-based drug complexes and their pharmacodynamics in vivo.
By directly observing the trafficking of these therapeutic agents, the technique
provides a novel opportunity to advance our understanding of their metabolism
and the drug resistance of tumors. Furthermore, it will be possible to verify and
monitor therapy response at an early stage allowing to tailor treatment, thereby
avoiding unnecessary side effects and improving treatment outcomes.
5.3 Endogenous Trace Elements
Trace elements are dietary minerals required for the proper functioning of the
organism. These elements, including Cr, Mn, Fe, Co, Ni, Cu, Zn, Se, Mo, and I,
occur at very low concentrations (<100 ppm) under normal conditions and are
indispensable to the biosynthesis of special metalloproteins and metalloenzymes.
XF studies have shown that the concentration of these elements is perturbed in
various disease states. For instance, elevated levels of copper were observed in breast
cancer [36], while abnormally low levels of zinc were found in prostate cancer
[37]. Iodine is also accumulated excessively in certain types of breast cancers that
overexpress the sodium-iodine symporter [38]. The potential to image endogenous
contrast mechanisms in vivo is unique and will provide new biological insights.
5.4 X-Ray Luminescent Contrast Agents
The majority of studied X-ray luminescent contrast agents are rare-earth nanoprobes
which consist of a lanthanide-doped host material surrounded by a non-doped shell
[39]. The luminescent behavior of the lanthanide-doped material has been well
characterized over the years due to the broad use of scintillation materials in X-ray
medical imaging applications [40]. Different experiments were conducted using
BaYF 5 , NaYF 4 , or NaLuF 4 doped with ytterbium (Yr) and erbium (ER), or
X-Ray Excited Fluorescent Materials for Medical Application
135
Metallodrugs are designed to induce pharmacological effects by interacting with
proteins (in particular with catalytically active enzymes) or directly with DNA
[35]. Because of their unique properties, metallodrugs are the subject of intense
research efforts. Platinum-based complexes are examples of the most widely used
anticancer agents. Currently researched compounds are mainly based on platinum
but also other metals such as ruthenium, titanium, gallium, or silver are under
investigation. Until now, no imaging technique was available to visualize the
distribution of these drugs in living subjects. Because metals such as platinum
emit energetic characteristic X-rays, they are highly amenable to imaging via
XFCT [18]. XFCT will play a pivotal role in the biological characterization and
optimization of metal-based drug complexes and their pharmacodynamics in vivo.
By directly observing the trafficking of these therapeutic agents, the technique
provides a novel opportunity to advance our understanding of their metabolism
and the drug resistance of tumors. Furthermore, it will be possible to verify and
monitor therapy response at an early stage allowing to tailor treatment, thereby
avoiding unnecessary side effects and improving treatment outcomes.
5.3 Endogenous Trace Elements
Trace elements are dietary minerals required for the proper functioning of the
organism. These elements, including Cr, Mn, Fe, Co, Ni, Cu, Zn, Se, Mo, and I,
occur at very low concentrations (<100 ppm) under normal conditions and are
indispensable to the biosynthesis of special metalloproteins and metalloenzymes.
XF studies have shown that the concentration of these elements is perturbed in
various disease states. For instance, elevated levels of copper were observed in breast
cancer [36], while abnormally low levels of zinc were found in prostate cancer
[37]. Iodine is also accumulated excessively in certain types of breast cancers that
overexpress the sodium-iodine symporter [38]. The potential to image endogenous
contrast mechanisms in vivo is unique and will provide new biological insights.
5.4 X-Ray Luminescent Contrast Agents
The majority of studied X-ray luminescent contrast agents are rare-earth nanoprobes
which consist of a lanthanide-doped host material surrounded by a non-doped shell
[39]. The luminescent behavior of the lanthanide-doped material has been well
characterized over the years due to the broad use of scintillation materials in X-ray
medical imaging applications [40]. Different experiments were conducted using
BaYF 5 , NaYF 4 , or NaLuF 4 doped with ytterbium (Yr) and erbium (ER), or
X-Ray Excited Fluorescent Materials for Medical Application
135