17 October 2012

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.

  1. 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 
  2. Dextran /PHARMACOSMOS; http://www.dextran.net/dextran-chemistry.html
  3. 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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