Professor wants to develop a radioactive precision missile to target brain cancer

Every year, around 300 Danes, including 30 children, are diagnosed with glioblastoma – a malignant type of brain cancer that is resistant to all therapies currently available to medical professionals.

Glioblastoma cells cannot be removed surgically, by chemotherapy or by irradiation, partly because it is immensely difficult and requires extreme care to perform surgery on the brain without damaging its many vital functions.

Consequently, even with the best possible treatment, the surviving cancer cells will quickly spread and continue wreaking havoc until the patient dies.

‘The average survival rate after diagnosis of glioblastoma is 14 months. Unfortunately, this has largely remained unchanged for the past 15 years. Even though research is being conducted all over the world, no-one has yet been able to develop an effective treatment for this particular form of brain cancer,’ says Andreas Kjær, professor of nuclear medicine and molecular imaging at the University of Copenhagen and Rigshospitalet, where, together with his research team, he is attempting to design a completely new type of treatment for glioblastoma.

He has received funding for his research from, among others, the Lundbeck Foundation, which recently awarded Professor Kjær a six-year research grant worth DKK 40 million.

And, if they remain on schedule, the first patient trials with the new glioblastoma treatments will commence during this period.

Not all cancer cells disappear
For many years now, Professor Kjær has been working on developing specific tracers – probes – for use in PET scanning.

A number of variants of these tracers will play a key role in the new methods he will be designing for treatment of glioblastoma. Professor Kjær explains that the primary function of the tracers will be to launch a direct attack on the glioblastoma cells:

‘One of the problems with glioblastoma is the very special way in which this form of brain cancer spreads. You can see the actual tumour on an MRI scan, but if you attempt to remove it surgically, you won’t be able to remove it all, because there are always tiny cancer islets – offshoots – in the vicinity of the tumour. These aren’t readily discernible and are, therefore, impossible to remove.’

So, the brain surgeon can excise the tumour – that is, if he can operate on the part of the brain where it is located – but the small islets will be left behind. As Professor Kjær says, the brain tumour then simply continues its fatal development:

‘By constructing a fluorescent tracer that latches onto the glioblastoma cells and makes them luminescent, we hope to make it easier for the surgeon to see the cancer cells while operating. This should enable surgeons to remove the islets – if, of course, they’re located in a part of the brain that is operable.’

The fluorescent tracers that latch onto the glioblastoma cells and cause the tumour to light up have been tested in animal trials – and the technique works so well that Professor Kjær and his colleagues will now seek the permission of the Danish Medicines Agency to test the tracing technique in human glioblastoma surgery. If they receive this permission, the first surgery will take place in 2020.

Bombarding the cancer cells
Today, chemotherapy and radiation therapy are part of the treatment given to glioblastoma patients: both when surgery is performed and when an operation is impossible due to the location of the tumour. Professor Kjær explains:

‘Patients are given radiation treatment from the outside, through the cranium wall. The challenge is to ensure that we only irradiate the glioblastoma cells, so that we don’t damage the healthy cells adjacent to the tumour. But, because it’s impossible to aim so precisely, a considerable amount of healthy brain tissue will inevitably also be irradiated. We’ll work on identifying a new solution for this, too, using a tracer tailored to act as a precision missile.’

Put extremely simply, the precision missiles that are being developed consist of a probe with a radioactive substance attached to the tail.

This radioactive substance emits short-range radiation able to kill cancer cells, and the tracer is constructed in such a way as to ensure that it only binds to the surface of brain cancer cells. Professor Kjær explains:

‘The precision missiles will seek out the glioblastoma cells in the brain and will then go in search of them in other parts of the body to which they may have spread through the bloodstream. When these precision missiles meet a brain cancer cell they’ll bind – and we’ll irradiate it. Ideally, because the radiation remains within a range of one millimetre, the precision missiles will kill all of the brain cancer cells without causing extensive damage to healthy tissue at the same time.’

Professor Kjær expects to be able to test the precision missiles on Danish glioblastoma patients over the course of the next six years. However, he says that, before they can do this, the technique must be tested in mice, and they will start on this very soon.

The Rigshospitalet, University of Copenhagen, research team will take part of a glioblastoma tumour removed from a patient’s brain during surgery to test the precision missiles on the tumours of real patients. Professor Kjær explains:
‘To begin with, we’ll mature these cancer cells by inserting them under the skin of a mouse. Once the cells have matured to the right stage, we’ll place them in the mouse’s brain – like a brain tumour – and then try to combat the tumour with the help of the small, radioactive precision missiles.’
If the outcome of these trials is satisfactory, Andreas Kjær and his colleagues will apply to the Danish authorities for permission to use the missiles in experimental treatment of glioblastoma patients.

When new medical therapies are designed, the road from idea to human trials is generally very long, partly because we need to safeguard against side effects.
However, a fast track principle applies to medicines for fatal illnesses for which there are currently no effective treatments; as is the case with glioblastoma.
This means that, in certain circumstances, a promising therapy may be brought more quickly to human trials than researchers would usually be able to manage. Professor Kjær explains:

‘Our plan is, initially, to seek permission to test the precision missiles for treatment of adults with glioblastoma. If the outcome is positive, we’ll then attempt to use the technique to treat children with this form of brain cancer. All things being equal, children with the disease have the most to gain because they’re just starting out in life.’