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.
That’s according to the Head of Nuclear Medicine Department at University of Pretoria and Steve Biko Academic Hospital, Professor Mike Sathekge, who says this modality changes cancer management in over half the patients he and his colleagues handle. He goes so far as to say that 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 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, (most whom are active), only 13 public nuclear medicine units and about 46 in private (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 metropoles. 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. Sathekge says, “State-sector scans cost around half of those in the private sector.” That’s around R12 000 – R14 000 for private or medical aid patients.
“Sometimes the therapeutic isotope required can quickly use up any medical aid limits, at up to R58 000 per 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’ve been imaged (at Steve Biko Academic Hospital) via the PET scanner for prostate (not all needing Lutetium), an estimated 300 were excluded due to being unable to afford the isotope. Only 30 could afford it and thus benefitted.
For thyroid cancer patients however, the good news is that the treatment is most often within budget reach. 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, making it the third largest producer and supplier globally.
Nuclear medicine uses small amounts of radio isotopes (ingested, inhaled or injected), to find disease as early as a patient presents. Liquid substances known as radionuclides (tracers or radiopharmaceuticals) release low levels of radiation. Body tissues affected by diseases such as cancer absorb more of the tracer than normal tissues, enabling special cameras to pick up the pattern of radioactivity to create pictures showing where the tracer travels and collects. If cancer is present, the tumour may show up as a ‘hot spot’ (increased cell activity and tracer uptake). Depending on the type of scan done, the tumour might instead be a ‘cold spot’ (decreased uptake and less cell activity). 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 (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.
Sathekge says 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, (depending on the isotope used), 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”.
The ‘tipping point,’ came in the late 1990s via molecular imaging in the form of PET with the 18F-labeled glucose analog, fluorodeoxyglucose (FDG), and has revolutionized 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 of theranostics is its revolutionary approach that promises improved therapy selection on the basis of specific molecular features of disease, greater predictive power for adverse effects, and new ways to objectively monitor therapy response.
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. Sathekge emphasises that although raising awareness of nuclear medicine among colleagues is vital, all treatment is multidisciplinary. “We don’t want to do it alone – there can be no unilateral decisions,” he adds.
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 via 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/Steve Biko Academic Hospital, where the national pace is being set, research on prostate cancer centres on prostate-specific membrane antigen (PSMA), which is highly sensitive for the detection of disseminated prostate cancer, is underway. 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 bi-monthly and their prostate-specific antigen response was 7%, which he calls exciting progress. Preliminary results are expected by late 2017. 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 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 due 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 and the technology has already been successfully introduced nationally and continentally for prostate cancer and in patients with inoperable neuro-endocrine tumours with a median Progression Free Survival of 20 months (in the absence of significant side effects). The results are about to be tested in a multi- national study, known as COMPLETE.
Sathekge reveals that the theranostic research approach, using new molecules to target melanomas, was also part of additional research but 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.
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).
- Professor Sathekge is Head of Nuclear Medicine: University of Pretoria & Steve Biko Academic Hospital, Chair: South African Medical Research Council and President: The Colleges of Medicine of South Africa.