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05 February 2019 | Story Leonie Bolleurs
Cancer research
Inorganic Chemistry supervisors in the Radiopharmacy Laboratory during the preparation of a typical complex mixture to see how fast it reacts. If radioactivity is used, it is handled behind the grey lead-metal shield to minimise radiation of the researcher. Here are, from the left, front: Dr Marietjie Schutte-Smith, Dr Alice Brink (both scholars from the UFS Prestige Scholar Programme), and Dr Truidie Venter (all three are Thuthuka-funded researchers). Back: Prof André Roodt and Dr Johan Venter. (Not present: Prof Deon Visser and Amanda Manicum).

Imagine that you have been diagnosed with bone cancer and only have six months to live. You are in a wheelchair because the pain in your legs is so immense that you can’t walk anymore – similar to a mechanism eating your bones from the inside.

You are lucky though, since you could be injected with a drug to control the pain so effective that you will be able to get out of the wheelchair within a day-and-a-half and be able to walk again. Real-life incidents like these provide intense job satisfaction to Prof André Roodt, Head of a research group in Inorganic Chemistry at the University of the Free State (UFS). The research, which is conducted by the Inorganic Group at the UFS, contributes potentially to the availability of pain therapy that does not involve common drugs, but improves the quality of life for cancer patients.

The research conducted by the Inorganic Group under the leadership of Prof Roodt, plays a major role in the clever design of model medicines to better detect and treat cancer.

The Department of Chemistry is one of approximately 10 institutions worldwide that conducts research on chemical mechanisms to identify and control cancer. “The fact that we are able to cooperate with the Departments of Nuclear Medicine and Medical Physics at the UFS, the Animal Research Centre, and other collaborators in South Africa, Switzerland and the USA, but especially the methodology we utilise to conduct research (studying the chemical manner in which drugs are absorbed in cancer as well as the time involved), enhances the possibility of making a contribution to cancer research,” says Prof Roodt.

Technique to detect cancer spots on bone
According to the professor, there are various ways of detecting cancer in the body. Cancer can, inter alia, be identified by analysing blood, X-rays (external) or through an internal technique where the patient is injected with a radioactive isotope.

Prof Roodt explains: “The doctor suspects that the patient has bone cancer and injects the person with a drug consisting of an isotope (only emits “X-rays” and does no damage to tissue) that is connected to a phosphonate (similar to those used for osteoporosis). Once the drug (which contains the isotope Technetium-99m) is injected, it moves to the spot on the bone where the cancer is located. The gamma rays in the isotope illuminate the area and the doctor can see exactly where treatment should be applied. The Technetium-99m has the same intensity gamma rays as normal X-rays and therefore operates the same as an internal X-ray supply.” With this technique, the doctor can see where the cancer spots are within a few hours.

The same technique can be used to identify inactive parts of the brain in Alzheimer patients, as well as areas of the heart where there is no blood supply or where the heart muscle is dead.

Therapeutic irradiation of cancer
For the treatment of pain connected with cancer, the isotope Rhenium-186 is injected. Similar to the manner in which the Technetium-99m phosphonate compound is ingested into the body, the Rhenium-186 phosphonate travels to the cancer spots. Patients thus receive therapeutic irradiation – a technique known as palliative therapy, which is excellent for treating pain. A dosage of this therapy usually lasts for about two months.

The therapy is, however, patient specific. The dosages should correspond with the occurrence and size of cancer spots in the patient’s body. First, the location of the cancer will be determined by means of a technetium scan. After that, the size of the area where the cancer occurs has to be determined. The dosage for addressing total pain distribution will be calculated according to these results.

Technique to detect cancer spots on soft tissue

Another technique to detect cancer as spots on bone or in soft tissue and organs throughout the body is by utilising a different type of irradiation, a so-called PET isotope. The Fluorine-18 isotope is currently used widely, and in Pretoria a machine called a cyclotron-facility was established by Dr Gerdus Kemp, who is a former PhD graduate from the Inorganic Research Group. The F-18 is then hidden within a glucose molecule and a patient will be injected with the drug after being calmed and after the metabolism has been lowered considerably. The glucose, which is the 'food' that cancer needs to grow, will then travel directly to the cancer area and the specific area where the cancer is located will thus be traced and ‘illuminated’ by the Fluorine-18, which emits its own “X-rays”.

In the late 80s, Prof Roodt did his own postdoctoral study on this research in the US. He started collaborating with the Department of Nuclear Medicine at the UFS in the early 90s, when he initiated testing for this research.

Through their research of more than 15 years, the Inorganic Group in the Department of Chemistry has made a major contribution to cancer research. Research on mechanisms for the detection of cancer, by designing new clever chemical agents, and the chemical ways in which these agents are taken up in the body, especially contributes to the development in terms of cancer therapy and imaging, and has been used by a number of hospitals in South Africa.

The future holds great promise
Prof Roodt and his team are already working on a collaborative study between the UFS and Kenya/ Sudan/ Lesotho. It involves the linking of radio isotopes, as mentioned above, to known natural products (such as rooibos tea and South African aloe extracts), which possess anti-cancer qualities. A preliminary World Patent has also just been filed in more than 30 countries on potential new cancer medicines which contain both an imaging isotope and a therapy isotope/ compound.

News Archive

Research by experts published in Nature
2011-06-02

 
The members of the research group are, from the left, front: Christelle van Rooyen, Mariana Erasmus, Prof. Esta van Heerden; back: Armand Bester and Prof. Derek Litthauer.
Photo: Gerhard Louw

A  research article on the work by a team of experts at our university, under the leadership of Prof. Esta van Heerden, and counterparts in Belgium and the USA has been published in the distinguished academic journal Nature today (Thursday, 2 June 2011).

The article – Nematoda from the terrestrial deep subsurface of South Africa – sheds more light on life in the form of a small worm living under extreme conditions in deep hot mines. It was discovered 1,3 km under the surface of the earth in the Beatrix Goldmine close to Welkom and is the first multi-cellular organism that was found so far beneath the surface of the earth. The worm (nematode) was found in between a rock face that is between 3 000 and 12 000 years old.

The research can shed some new light on the possibility of life on other planets, previously considered impossible under extreme conditions. It also expands the possibilities into new areas where new organisms may be found.

These small invertebrates live in terrestrial soil subjected to stress almost for 24 hours They live through sunshine, rain, scorching temperatures and freezing conditions. Through time they developed a means to cope with harsh conditions. Terrestrial nematodes (roundworms, not to be confused or related to earthworms) are among those very tough small invertebrates that deal with those conditions everywhere. After insects they are the most dominant multi-cellular (metazoan) species on the planet having a general size of 0,5 to 1 mm and are among the oldest metazoans on the planet, Nature says in a statement on the article.

They inhabit nearly every imaginable habitat form the deep seas to the acid in pitcher . Some nematodes simply eat bacteria and these are the ones we study here. Terrestrial nematodes have developed a survival stage that can take them through hard times (absence of food, extreme temperatures, too little oxygen, crowding, and more).

At the head of the research was Prof. Gaetan Borgonie of the Ghent University in Belgium and a world leader in the discipline of nematode research. He was brought into contact with the South African research leader, Prof. Esta van Heerden, who set up a cooperation agreement with the University of Ghent and Prof. Borgonie. Prof. Van Heerden manages the Extreme Biochemistry group at the UFS and the research was funded by several research grants.

The search for worms began in earnest in 2007, but it was soon clear that the sampling strategy was insufficient. A massive sampling campaign in 2008-2009 in several mines led to the discovery of several nematodes and the new nematode species Halicephalobus mephisto. It is named after the legend of Faust where the devil, also known as the lord of the underworld is called Mephistopheles.

Nature says special filters had to be designed and installed on various boreholes. Unfortunately, there is no easy way of finding a magic formula and designs had to be adapted by trial and error; improving existing designs all the time. The work of the UFS Mechanical Workshop, which manufactured, adapted and helped design it, was crucial in this respect. Filters were left on the holes for varying periods, sometimes for a few hours and sometimes for months. Prof. Derek Litthauer from the UFS played a big role in sampling, filter designs and coming up with ideas for names for the new nematode with Prof. Borgonie.

Research showed that the nematodes can live in the deep for up to 12 000 years. Three students – Armand Bester, Mariana Erasmus and Christelle van Rooyen from the UFS – did the work on this.

The importance of multi-cellular animals living in the ultra-deep subsurface is twofold: The nematodes graze on the existing bacterial population and influence their turnover. Secondly, if more complex multi-cellular organisms can survive in the deep subsurface on earth, this may be good news when looking for life on other planets where the surface is considered too inhospitable (e.g. Mars). Complex life forms can be found in ecosystems previously thought to be uninhabitable. Nature says this expands the possibilities into new areas where new organisms may be discovered.

Future research will focus on selective boreholes to look for more metazoans, so that a better idea of the complexity of the ecosystems there can be obtained. It will also look for metazoans in the deep subsurface on other continents to determine similarities and differences.

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