Most people have, in some way or other, been affected by cancer, whether through the loss of a loved one or a personal fight against the big C, a dreaded and often incurable disease. Worldwide approximately 8.2 million people die from cancer every year, and four million of those deaths are premature (people aged between 30 and 69 years).

Researchers in the Department of Nuclear Medicine at the University of Pretoria who are trying to change the bleak prospect faced by cancer patients are currently involved in breakthrough research and treatment that is proving to have such successful results that one cannot help but become hopeful that there might be light at the end of the very dark tunnel that is cancer.

World Cancer Day is celebrated annually on 4 February. The Cancer Day theme for the past three years, ending in 2018, has been, ’I Can. We Can’, which is aimed at encouraging people to make an impact and lower the risks of cancer. The Department of Nuclear Medicine, headed by Prof Mike Sathekge, is determined to prove that they can.

Targeted alpha therapy (TAT), or alpha radiation, is a fairly new approach to cancer treatment and is based on the coupling of alpha particle-emitting radioisotopes to tumour-selective carrier molecules, such as monoclonal antibodies or peptides. In simpler terms, targeted alpha therapy uses drugs to target specific genes or proteins that are present in cancer cells to stop the cancer from growing and spreading. The Department of Nuclear Medicine at the Steve Biko Academic Hospital is one of only three platforms in the world that is using this form of treatment to treat cancer, specifically advanced-stage prostate cancer, by using alpha isotopes known as Ac-225-PSMA. This is not only remarkable, but the fact that UP was selected to use this form of treatment also highlights its exceptional leadership in the area of targeted radionuclide therapy. The Department presented the first in-human treatment concept with ²¹³Bi-PSMA-617 in a patient with metastasised castration-resistant prostate cancer (mCRPC), which had reacted progressively under conventional therapy. (²¹³Bi-PSMA-617 is a daughter of ²²⁵Ac225 and another form of targeted radionuclide therapy.)

What makes alpha therapy so effective, compared to other radio-immunotherapy treatments like beta therapy, is its ability to kill the cancer cells by causing double-strand breaks to the cancer’s DNA molecules and cluster breaks. ’Alpha radiation can kill cells that otherwise exhibit resistance to treatment with beta- or gamma-irradiation or chemotherapeutic drugs, and thus offers a therapeutic option for patients resistant to conventional therapies,’ said Prof Sathekge, who leads the TAT. He further explained that because alpha radiation has a very short range, cancer cells can be specifically targeted while sparing healthy tissue.

Prostate cancer has a specific ’lock’, known as prostate-specific membrane antigen (PSMA), which is found on the surface of each prostate cancer cell. Very specific molecules known as radioactive isotopes have been developed that bind only to PSMA. This process, called molecularly targeted radiotherapy, includes alpha and beta targeted therapy. While beta-emitter targeted therapy has been used for longer and certainly has an important role in cancer therapy, the link of actinium (an alpha emitter) to PSMA is where the breakthrough in cancer research lies.

Patients, particularly those whose cancer has reached a very advanced stage, undergo an imaging process to pick up abnormal cells and, depending on the aggressiveness of the cancer, Prof Sathekge and his team are able to determine the course of radioactive therapy required and to administer TAT. These patients are usually those who have not shown any positive reactions to conventional treatments such as chemotherapy and hormone therapy.

As a leading expert in this field, Prof Sathekge is in high demand and receives regular queries from professionals from around the world who are interested in using this treatment. He explained that, due to the international security issues around nuclear use, there are certain sensitivities relating to producing and administering alpha therapy. At this stage it can be produced only by the European Union’s Joint Research Centre (JRC), which is based in Germany. The JRC supplies it to UP for administration to patients. It is hoped that in time local platforms, such as NTP Radioisotopes, a subsidiary of the South African Nuclear Energy Corporation (Necsa), will be able to start producing it to make the treatment more accessible.  Prof Sathekge noted that NTP is a world-class organisation and one of the world leaders in beta-targeted therapy production. One of the important and useful beta-targeted therapies produced by NTP is ¹⁷⁷Lu. This is the most widely available therapy for both prostate (¹⁷⁷Lu-PSMA) and neuroendocrine cancer (¹⁷⁷Lu-DOTATATE).

In the future, the Department plans to look into the efficacy of alpha-targeted therapy for the treatment of melanoma and other cancers, and to gain a better understanding of epigenetics, which is the study of heritable changes in gene function that do not involve changes in the DNA sequence, in order to better understand the spread of cancer.

CANSA reports that in South Africa, cancer is under-reported due to the lack of a comprehensive cancer surveillance system. This is why Prof Sathekge believes that in order to achieve optimal success in treating any form of cancer, a multidisciplinary approach is essential, from diagnosis all the way through to treatment. This approach should be very patient specific and the course of treatment should be determined based on an individualised screening of each patient. The team of experts should include nuclear physicians, oncologists, radiologists and surgeons working together to determine the best course of treatment for the patient.