Going nuclear: Beating cancer on a molecular level

Nuclear scans provide the best possible images of internal organs and tissues based on the body’s chemistry. They have, in the past three years, moved from a purely diagnostic function to providing actual therapy with previously unheard-of success.

According to the Head of the Nuclear Medicine Department at the University of Pretoria and Steve Biko Academic Hospital, Professor Mike Sathekge, this modality changes cancer management in over half the patients he and his colleagues handle. He says if people are unable to access nuclear medicine, the likelihood of mismanagement increases because the treating physician may not realise the full extent of the disease. Many oncologists are not yet aware of the benefits of nuclear medicine and there is an overwhelming need to include this modality of diagnostic-therapeutic treatment where indicated.

Cost and availability are major barriers to access, with 64 nuclear physicians in the country, only 13 public nuclear medicine units and about 46 units in private healthcare (the private sector units tend to open and close over time and have the same owners).

Positron emission tomography/computed tomography (PET/CT) scanners are spread across the main city centres. While nearly all nuclear medicine departments in the public and private sectors have gamma cameras for functional scans of the brain, thyroid, lungs, liver, gallbladder, kidneys and skeleton, the greater need is for PET/CT diagnosis and therapy. If you live in Limpopo or the North West provinces, you won’t find PET/CT scanners. But if you’re from Gauteng, Durban or Cape Town, your chances of accessing this technology are greater. Prof Sathekge says, “State-sector scans cost around half of those in the private sector.” The cost is around R12 000 to R14 000 for private or medical aid patients.

Radioisotope therapy is a procedure in which a liquid form of radiation is administered internally through infusion or injection to treat cancerous cells with minimal damage to the normal surrounding tissue. “Sometimes the therapeutic isotope required can quickly use up any medical aid limits, at up to R58 000 for each cycle, with up to four cycles sometimes needed. We’re speaking to Pelindaba (where the Nuclear Medical Corporation of South Africa is situated) to try and make lutetium (the most in-demand, expensive isotope) cheaper,” he says. To date, of 450 patients who have been imaged (at Steve Biko Academic Hospital) by the PET scanner for prostate cancer (not all needing lutetium), an estimated 300 were excluded because they couldn’t afford the isotope treatment. Only 30 could afford it and, as a result, benefitted.

For thyroid cancer patients, however, the good news is that the treatment is most often within budget reach. Prof Sathekge says the provision of lutetium is expected in the near future and this will make access wider and cheaper.

NTP Radioisotopes SOC Ltd, a subsidiary of the South African Nuclear Energy Corporation (Necsa), produces a quarter of the world’s medical radioisotopes, allowing for about 40 million medical diagnostic images every year. It is, consequentially, the third largest producer and supplier globally.

How nuclear medicine works

The tipping point came in the late 1990s through molecular imaging in the form of PET with the ¹⁸F-labeled glucose analog, fluorodeoxyglucose (FDG), and has revolutionised medicine, most significantly in oncology. FDG PET, now synonymous with molecular imaging, has become an integral part of patient management for cancer staging, restaging and monitoring therapy response for a number of reimbursable indications. From this, nuclear medicine physicians continue to develop platforms for identifying new biologic targets that treat the way in which cancer tumours are vascularised or protruded and that detect hypoxia.

Nuclear medicine scans may miss very small tumours and will not always tell whether a tumour is really cancer, but they show internal organ and tissue problems (functional issues) far better than other imaging tests. For example, bone scans that show hot spots on the skeleton are usually followed by X-rays of the affected bones since these are better at showing detail of bone structure. Some nuclear medicine scans are also used to measure heart function – important when undergoing surgery, chemotherapy or radiation treatment

Prof Sathekge says that a common misconception is that the radiation is harmful or will cause infertility. “People don’t understand that the radiation will be out of the system from within two hours to a maximum of two weeks depending on the type of the tracer and the indication. We give the bare minimum to get the desired effect,” he adds.

Molecular theranostics = diagnostic tests with therapeutic intervention

The tipping point came in the late 1990s through molecular imaging in the form of PET with the ¹⁸F-labeled glucose analog, fluorodeoxyglucose (FDG), and has revolutionised medicine, most significantly in oncology. FDG PET, now synonymous with molecular imaging, has become an integral part of patient management for cancer staging, restaging and monitoring therapy response for a number of reimbursable indications. From this, nuclear medicine physicians continue to develop platforms for identifying new biologic targets that treat the way in which cancer tumours are vascularised or protruded and that detect hypoxia.

This has enabled nuclear medicine physicians to be leaders in molecular theranostics, which can be described as a system that integrates a diagnostic test with a therapeutic intervention. The excitement around theranostics is because of its revolutionary approach that promises:

• Improved therapy selection based on specific molecular features of disease
• Greater predictive power for adverse effects
• New ways to monitor therapy response objectively.

Types of cancer for which nuclear medicine works best are neuro-endocrinal tumours, prostate and thyroid cancer and bone pain palliation (slowing cancer growth), while in children it is also used for neuroblastomas.

With prostate and neuro-endocrinal cancer the success rate is about 80% (especially when prostate cancer recurs), while for thyroid cancer it’s in the 90% range. Prof Sathekge emphasises that although raising awareness of nuclear medicine among his colleagues is vital, all treatment is multidisciplinary. “We don’t want to do it alone – there can be no unilateral decisions,” he adds.

Advances in cancer treatment

Prof Sathekge says the research horizon in prostate and breast cancer and neuro-endocrine tumours is very promising. Current work is already providing the basis for successful radionuclide therapy by using the theranostic approach which integrates diagnostic testing to determine the presence of a molecular target for which a specific treatment or drug is intended. This is already available to everyone who can afford it.

In his department at the University of Pretoria and Steve Biko Academic Hospital where the national pace is being set, research is underway on prostate cancer centres for a prostate-specific membrane antigen (PSMA), which is highly sensitive for the detection of disseminated prostate cancer. His team is also looking at PSMA-targeted treatment with different radionuclides and a combination of various therapies for castration (surgical or chemical) resistant prostate cancer.

Several patients have received up to four cycles of a very specific drug combination twice a month and their prostate-specific antigen response was 7%, a result that Prof Sathekge calls exciting progress. The trial also includes finding the optimum dose, tolerance, and the frequency and timing to initiate therapy.

The selective expression of PSMA in the tumour-associated neo-vasculature (formation of new blood vessels in the circulatory system) of a wide variety of solid tumours, including breast cancer, is another area of promising research, though still in the experimental stage. The work in these areas by Prof Sathekge’s team is breaking new ground internationally.

They’ve also made solid progress with the characteristically diverse neuro-endocrine tumours (NET) which so often present late owing to non-specific symptoms, taking imaging advantage of specific tumour-expressing receptors. For some eligible patients, Peptide Receptor Radionuclide Therapy (PRRT) can then follow. This NET treatment is currently available to anyone who can afford it. The technology has already been successfully introduced nationally and continentally:

• For prostate cancer
• In patients with inoperable neuro-endocrine tumours.

There’s been a median progression-free survival of 20 months in the absence of significant side effects and the results are about to be tested in a multinational study.

Prof Sathekge reveals that the theranostic research approach of using new molecules to target melanomas was also part of additional research. He declined to reveal details as confidentiality was a condition of a major Belgian funding grant facilitated by the National Research Foundation..

Other important projects involve service delivery for thyroid tumours and PhD work on cervical cancer – all currently being carried out by registrars.

Prof Sathekge’s contribution to the international PET/CT application on patients suffering from HIV/AIDS and tuberculosis has resulted in several highly acclaimed publications, garnered awards and led to his current presidency of the International Society of Radiolabeled Blood Elements (ISORBE).