Theranostics = Therapeutics + Diagnostics
- Before we go into the topic for today, we must take a quick look at the just recently held Nobel Prize awards (Science). Every year since 1901, the Nobel Prize has been awarded for accomplishments in physics, chemistry, physiology or medicine, literature and for peace. Alfred Bernhard Nobel, a Swedish chemist, engineer, innovator, and armaments manufacturer, held 350 different patents, dynamite being the most famous. He used his fortune to posthumously institute the Nobel Prizes. Three of the Nobel prizes are relevant to bioinformatics: Chemistry, Physics, and Physiology and Medicine
Nobel
Prize - Chemistry 2012
The Nobel Prize
in Chemistry 2012 was awarded jointly to Robert J. Lefkowitz and Brian K.
Kobilka" for studies of G-protein-coupled receptors" "The Nobel
Prize in Chemistry". Nobelprize.org. 12 Oct 2012 http://www.nobelprize.org/nobel_prizes/chemistry/
Nobel
Prize - Physics 2012
The Nobel
Prize in Physics 2012 was awarded jointly to Serge Haroche and David J.
Wineland "for ground-breaking experimental methods that enable measuring
and manipulation of individual quantum systems" "The Nobel Prize in
Physics". Nobelprize.org. 12 Oct 2012 http://www.nobelprize.org/nobel_prizes/physics/
Nobel
Prize - Physiology or Medicine 2012
The Nobel
Prize in Physiology or Medicine 2012 was awarded jointly to Sir John B. Gurdon
and Shinya Yamanaka "for the discovery that mature cells can be
reprogrammed to become pluripotent" "The Nobel Prize in Physiology or
Medicine 2012". Nobelprize.org. 12 Oct 2012 http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/
For more Nobel Prize info,visit
Nobel
Prize Main Web Page here
Regarding the prize for Chemistry involving G-Protein
Coupled Receptors, there is a noteworthy webpage dealing with this study and
development area. It is here
There are quite a few applications using the G-CPR
mechanism. One salient one has been in the chemistry of opioid substances in
the area of Structural Neurobiology. For more on this feature, kindly visit The StevensLaboratory
Having mentioned the above, we now move on to what may
be, in my opinion, the next arena for prize-winning developments.
Theranostics - Buzzword?, or, the next Big Thing?
- As mentioned earlier, Theranostics is an area of Medical
development that combines the principles of therapeutics and the processes of
diagnostics. It is touted as the very important facet of personalized Medicine,
pharmacogenomics, and molecular imaging. In this arena, a treatment option,
whether a patient can be either helped, or harmed by a treatment modality, can
be identified by imaging with nanopores, Quantum Dots, “tagged” immunoglobulins,
and others. What’s more is that theranostics aims to improve treatment outcomes
and the overall safety of the patient. On the other hand, the incorporation of
theranostics-based examinations and procedures requires much-needed resources
and more specialized training. So it must demonstrate cost-effectiveness across
the board. However, if developed
judiciously, theranostics may well be the eventual cost-effective business
model for this decade and the next and beyond.
Four Facets of Theranostics:
1. Diagnostic agent. 2. Carrier agent.
- We will start with the
diagnostic elements. There are many developments involving MRI and the use of
magnetic particles as the contrast agent. In atherosclerosis, for example, in
one study, atherosclerotic lesions (in rabbits) containing
accumulations of ultrasmall superparamagnetic iron oxides (USPIO) were
detected. The study protocol entailed performing
MRI and histologic studies to compare the uptake of dextran- and
mannan-dextran-coated USPIO (D-USPIO and DM-USPIO, respectively) by the
atherosclerotic walls of rabbits.[1] Dextran, a polysaccharide consisting of
many glucose units, has been used extensively clinically and in the
laboratory owing to its ability to exert osmotic pressure[2]. Mannans
are polysaccharides consisting of mannose
units and have diverse effects depending on the fraction used and the state of
purification. Mannans’ different mechanisms function at different levels
depending upon the specific phenomenon being influenced. Whereas dextran is a polymer of glucose,
yeast mannan is a polymer consisting entirely of mannose. In
this study, the investigators analyzed the signal to-noise ratio (SNR) of the
aortic wall in the same region of interest (ROI) and this was calculated in
both in vivo and in vitro studies. Next, histologic assessment was carried out
and showed that iron-positive regions were
significantly larger in rabbits injected with DM- rather than D-USPIO (P <
0.05) for all doses. The investigators suggest that DM-USPIO
is superior to D-USPIO for the study of atherosclerotic lesions in rabbits.
- This is an example of a diagnostic
agent, supermagnetic iron-oxide particles, delivered by the Mannan-Dextran as
the carrier agent, and the diagnostic modality was imaging via nuclear magnetic
resonance. It is almost like the proverbial golden shoe that fit the damsel’s
foot.
3. Targeting agent. 4. Therapeutic agent.
- Tests, regardless of modality, would be of no import if
there was no therapeutic system that would improve treatment outcome.
Currently, the standards for diagnostic examination are still in the hands of
the classic clinical laboratory, radiology, and physiologic signal analysis
(e.g. EEG, EKG, EMG). Nevertheless, clinical bedside diagnostics still play a
vital part of patient care. This is when the clinician and patient set the tone
for a better outlook, and where confidence between patient and clinician is
irreplaceable. Why? Because the ethical, psychological, and cognitive aspects
in Medical Practice dictate that the patient is above any test and of foremost
importance in decision making.
- Drug, chemical, or other treatment choices may be either
broad spectrum or highly selective. On many occasions clinicians are faced with
a patient with aggressive, late stage malignancy. When the most “suitable” (for reducing the
tumor) drug(s) are toxic to the patient, the physician has to maximize new
technology that may be of help. And this is an area where theranostics will be
of utmost help to the patient. After histologic and surgical classification (of
the tumor), the next appropriate step would be to utilize a diagnostic
procedure as mentioned in the study above, or other specialized imaging
modality.
- Quercetin, a plant-derived flavonoid, is derived from
quercetum (oak forest), and is a hydrophobic antioxidant-- which purportedly scavenges
damaging particles in the body known as free radicals, which damage cell
membranes, tamper with DNA, and even cause cell death. Found in fruits,
vegetables, leaves and grains, it has been used since the late 1800s for a wide
variety of purposes. It is sold as a herbal dietary supplement, and touted to
have anti-infllammatory, anti-viral, and anti-cancer agent, to name a few
properties. While neither the US FDA nor the American Cancer Society have approved
quercitin for cancer or any medical condition, it has been the subject of
research until now because of its potential anticancer activity.
- In one study, quercitin was loaded into monomethoxy
poly(ethylene glycol)-poly(ε-caprolactone). These loaded micelles (QU/MPEG-PCL)
given via intravenous route significantly suppressed the growth of
established xenograft A2780S ovarian tumors through causing cancer cell
apoptosis and inhibiting angiogenesis in vivo. Furthermore, the anticancer
activity of quercetin on ovarian cancer cells was studied in vitro. [3]
This is an example of nano-formulation of treatment agent (quercitin) and drug
delivery agent (MPEG-PCL).
- We have talked about a few examples where new
technologies improve health outcome, or at least identified available tools in
theranostics, which make it more possible to select the treatment of choice in
difficult clinical circumstances. A thorough understanding of the potentials of
theranostics, as well as its current
limitations will make us more competent in our own sphere of work. While this
management modality is still in its infancy, a good systematic review and analysis of
clinical and laboratory data will allow us to wield new weapons in our fight
against disease.
References:
- Tsuchiya K, Nitta N, Sonoda A, Nitta-Seko A, Ohta S, Takahashi M, Murata K, Mukaisho K, Shiomi M, Tabata Y, Nohara S.;Evaluation of atherosclerotic lesions using dextran- and mannan-dextran-coated USPIO: MRI analysis and pathological findings. Int J Nanomedicine. 2012;80. Epub 2012 May
- Dextran /PHARMACOSMOS; http://www.dextran.net/dextran-chemistry.html
- Xiang Gao , BiLan Wang, XiaWei Wei , Ke Men , Fengjin Zheng , Yingfeng Zhou , Yu Zheng , MaLing Gou , Meijuan Huang, Gang Guo, Ning Huang, ZhiYong Qian and Yuquan Wei Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer Nanoscale, 2012, Advance Article
- Stay focused. Work smart. 'Til the next...
- Fernando Yaakov Lalana, M.D.
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