First-in-human anti-cancer procedure brings hope

Posted on August 12, 2015

Cancer affects the lives of thousands of people every day. Normally our bodies produce new cells as they are needed, but occasionally, this process goes awry and new cells start growing when they are not needed while old cells do not die when they should. These extra cells form masses called tumours, which can be either benign or malignant. The malignant tumours are known as cancer. Cancer cells that break off from a primary tumour and enter the bloodstream or lymph vessels can reach nearly all tissues of the body. Bones are a common place for these cancer cells to settle and start growing. Tumours that result from these cells entering the bones are called bone metastases and can cause an extreme amount of pain and even skeletal fractures, resulting in a tremendous reduction in the patient’s quality of life. Once cancer has spread to the bones or to other sites in the body it is rarely curable, but various treatments are currently available to shrink, stop or at least slow the growth of cancer cells.

Prof Mike Sathekge, Head of the Department of Nuclear Medicine at the University of Pretoria (UP), says that the administration of bisphosphonates is an integral part of the treatment regimen commonly used today for patients with bone metastases. Bisphosphonates are antiresorptive medicines, which means that they slow or stop the natural process that dissolves bone tissue, resulting in maintained or increased bone density and strength.

‘Bisphosphonates have effects on the bone turnover and therefore affect bone metastases in different ways. Bisphosphonate treatment is now commonly used in the treatment of bone metastases as it delays the occurrence of skeletal events and hence showed improvements in the analgesia (pain mitigation) score,’ he said. He added that in recent years some of the most effective compounds identified for this purpose are nitrogen-containing heteroaromats such as zoledronate. Zoledronic acid is also used in chemotherapy to treat bone problems that may occur where cancer has spread to the bones.  

Targeted radionuclide therapy is another treatment for painful bone metastases that has long been used in nuclear medicine with excellent results in terms of pain relief. The greatest advantage of nuclear medicinal procedures is that they allow doctors to pinpoint molecular activity within the body and therefore offer the potential to identify disease at an early stage. They also allow doctors to gauge a patient’s immediate response to therapeutic interventions. During targeted radionuclide therapy, a doctor typically injects a single dose of a radiopharmaceutical into a vein from where it then travels to the areas of bone affected by cancer and emits radiation to kill the cancer cells. This treatment has proven very successful in terms of decreasing bone and tumour markers and indications are that it seems to enhance the overall survival rate of affected patients. The therapeutic effect is based on the synergy of an increased skeletal accumulation of bone-targeting agents on the metastatic foci and the nearby energy deposit of β- or α-particle irradiation.

In July this year, the Department of Nuclear Medicine at UP, in collaboration with Steve Biko Academic Hospital, ITG Isotopes Technologies Garching GmbH and NTP Radioisotopes SOC Ltd (a subsidiary of the South African Nuclear Energy Corporation), pioneered an exciting first-in-human anti-cancer procedure utilising a combination of radiopharmaceutical diagnosis and therapy. The procedure was developed by ITG and performed in South Africa for the very first time by Prof Sathekge and his team, along with Dr Sebastian Marx and Dr Marian Meckel of ITG and Dr Otto Knoesen of NTP. The diagnostic procedure was accomplished using positron emission tomography/computed tomography (PET/CT), which is a sophisticated nuclear medicine imaging technique.

This new and very promising procedure pioneered by Prof Sathekge and his team, uses a therapeutic emitter of low-energy β-particles that is commonly used in targeted radionuclide therapy. The substance used in the treatment, called DOTA-zoledronate, acts as an imaging agent in combination with the positron emitter 68Ga(III). This ‘theranostic’ approach, which entails a combination of therapy and diagnostics in which the same type of targeting molecule is used to obtain images and to deliver the dose of therapeutic isotope selectively to the tumour site, allows for patient-specific dose calculation directly related to the patient’s individual tracer uptake profile. It is expected that this procedure will be of great benefit to patients suffering the debilitating effects of metastatic bone disease.

To date, over 100 imaging procedures and treatments employing therapeutic radiopharmaceutical agents for treating neuroendocrine cancer have been performed with great success at Steve Biko Academic Hospital. In March this year Prof Sathekge also performed Africa’s first isotope-labelled theranostics procedure for prostate cancer. This type of procedure has since been done several times and will be performed routinely in future. The ground-breaking work that Prof Sathekge and his team at the Department of Nuclear Medicine have been doing will ensure that science is taken to the heart of health through thorough research on the diseases that impact the lives of so many people in our country every day.

 

- Author Ansa Heyl

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