An image of a scientist working in the lab, with her back turned to the camera.

This entry is part 6 of 11 in the series Radiotherapy

So far in this series, we’ve seen how doctors are fine-tuning external radiotherapy for a direct hit on tumour cells. In this post, we’re going inside the body to see how scientists are developing new ways of targeting cancer with radiotherapy from within.

There’s more to radiotherapy than machines that target cancer from the outside. In fact, using radiotherapy to target cancer from inside the body outdates the external approach.

Internal radiotherapy comes in two main forms: brachytherapy and liquid therapy.

Brachytherapy, which literally means ‘short-range therapy’, gets up-close and personal with cancer through a radioactive source that’s placed next to the tumour via surgery.

Whereas radioactive liquid therapy homes in on cancer via the bloodstream. In this case, radioactive molecules leave the blood and accumulate in tumours at a lethal dose to the cancer cells.

Both treatments share an important feature: the DNA-damaging radiation is delivered directly to tumour cells in a high dose, while surrounding healthy tissue receives a less damaging lower dose.

And now, researchers are working on new ways to make this targeting even more precise, so more patients can benefit.

Brachytherapy – getting up-close and personal with cancer

Brachytherapy isn’t new. In fact, something that resembled brachytherapy predated modern external radiotherapy, before scientists had figured out how to generate beams of radiation using a linear accelerator.

Marie Curie discovered radium in the 1890s, and a few years later it was used to treat cervical and womb cancers by being placed inside the body’s natural cavities, next to where the tumour was growing. Soon after, doctors started putting radium inside the body using surgery to treat breast, prostate, oesophageal and brain tumours.

Back then, doctors didn’t fully understand the dangers of radioactivity to healthy cells. Many damaged their own bodies by handling Radium without proper protection. Today, safer radioactive sources, smaller doses, and clever new methods are used to reduce risk.

100 years on, the basic features of brachytherapy haven’t changed. Today, there are two main types: high dose rate (HDR) and low dose rate (LDR) brachytherapy.

HDR brachytherapy gives the tumour a high radiation dose through a metal pellet that’s placed next to the tumour for short bursts of time.

LDR brachytherapy uses lower radiation doses for longer. In some cases, the radioactive pellet is placed directly next to the tumour for a few hours or days, but sometimes it’s inserted permanently. In this case, the pellet slowly releases radiation, which fades over several months.

Brachytherapy can be combined with other forms of cancer treatment, including surgery and external beam radiotherapy, to make it more effective.

What are the advantages of brachytherapy?

Radiation can damage healthy tissue, so researchers are working hard to develop new external radiotherapy techniques that spare healthy cells (such as IMRT or proton beam therapy). But brachytherapy has been doing this for years. Because of its short range, the radiation reaches few healthy cells so causes minimal collateral damage.

Its physical proximity to the tumour also keeps radiation focused on the tumour if it moves during treatment.

But despite its advantages, brachytherapy isn’t necessarily a better radiotherapy option. It’s most suitable for small, solid tumours that haven’t spread and are surgically accessible, most commonly cervical, prostate, breast and skin cancers.

Radioactive liquid therapy – homing in on cancer

Doctors can also give internal radiotherapy as a liquid containing radioactive molecules called radioisotopes. They travel through the bloodstream and accumulate in tumours where the radiation can penetrate and kill nearby cells.

Some radioisotopes target tumours naturally, such as radioactive iodine. Iodine is naturally absorbed by the thyroid gland to make hormones, and doctors can exploit this process using radioactive iodine as a treatment for thyroid cancer.

Research is uncovering ways to target radioactive substances to tumours in other parts of the body too. Scientists like Professor Katherine Vallis, based at Oxford University and funded by Cancer Research UK, are designing ways to exploit the differences between cancerous and normal tissues to improve radioactive liquid therapy.

“We select a targeting molecule that we know will selectively bind to a particular type of cancer cell,” says Vallis. “We then come up with a way of chemically attaching radioactive atoms to the carrier molecule.”

They’re testing this approach against certain types of cancer where cells produce too much of a molecule called EGFR on their surface. Here, the team uses a carrier molecule that sticks to EGFR, allowing it to accumulate around the cancer cells. Studies in the lab have shown that attaching radioactive Indium to the carrier molecule causes radiation to accumulate around cancer cells, stopping them from growing and dividing.

This concept has been tested in a trial of 15 women with EGFR-positive breast cancer. The treatment was well-tolerated and in 7 patients researchers were able to detect radiation accumulating inside the tumours.

The goal now is to increase the amount of radioactivity delivered to the tumour by attaching it to tumour-seeking nanoparticles.

Going deeper

It remains early days for the experimental forms of radioactive liquid therapy that Vallis and others are working on.

And for the treatments that are available, choosing a safe and effective dose is particularly difficult. Doctors base this decision on the patient’s weight, but this doesn’t take into account how much radioactivity that patient’s tumour will take up, or how much the neighbouring healthy tissue might be affected.

Scientists are working on ways to personalise the dose for each patient. One approach is to use the radioisotope as a signal for how much radiation has reached the tumour. Researchers hope to test this by giving a patient a small dose to see how much of it their tumour takes up, before applying a higher dose aimed at treating the cancer.

Vallis also has a vision that radioisotopes will one day be able to go further inside tumours than ever before. “We’re working hard to come up with ways to not only deliver radioactivity specifically to cancer cells, but actually design the drug in such a way that it enters the cancer cell and delivers the radioactive atoms direct to the DNA,”she says.

This would allow scientists to test radioactive atoms with an extremely short range – even smaller than the diameter of a cell. Once inside the target cancer cell, the radiation could reach and damage that cell’s DNA, but wouldn’t travel far enough to affect neighbouring healthy cells.

This has the potential to offer a more precise way of delivering radiotherapy to cancer cells while avoiding side effects.

And could take internal radiotherapy to new depths in the hunt for kinder, more effective treatments.