Neutrons from a research reactor are enabling R&D for new cancer therapies that will be more targeted and cause less collateral damage in healthy tissue.

The high neutron flux at the Institut Laue-Langevin (ILL) has produced samples of 161Tb, an isotope of terbium with better properties for cancer therapy than existing radiopharmaceutical treatments. Researchers led by Paul Scherrer Institute (PSI) and collaborating with ILL and Technical University of Munich, confirmed that 161Tb could be produced in sufficient quantity and quality for therapeutic use.

Radiopharmaceuticals (where a radioactive isotope is attached to a bioconjugate that selectively delivers it to cancer cells) are one of the best ways to diagnose and treat tumours. Radiopharmaceuticals are already very successful in fighting certain types of cancer, but those isotopes currently in use are not optimal for all therapeutic applications. They may cause collateral damage to healthy tissue or require an isolation of the patient during treatment. Better isotopes exist but are not commercially available. Advance in this field is crucially dependant on the availability of innovative isotopes for initial R&D, and then on the capability to produce large quantities for clinical applications. Today's 161Tb research is therefore an important step towards a new treatment that might improve the quality of cancer treatment and patient care.

What's so great about 161Tb?

"We have developed an innovative radiochemical method for the production of the novel therapeutic radioisotope 161Tb with highest quality suitable for medical applications. The production is scalable to provide enough 161Tb for the treatment of hundreds of patients per week." says Dr Konstantin Zhernosekov, Head of the Radionuclide Development Research Group at PSI.

161Tb has desirable decay properties for use in cancer therapy:

- Half life of 6.9 days - long enough to transport to hospitals but short enough not to pose long term issues of waste handling after excretion from the patient

- Emits low-energy β particles and low-energy electrons - results in a short cytotoxic range with minimal collateral damage to healthy tissue

- Emits a small amount of gamma radiation - enough to detect exactly where the radioisotope has been delivered to

161Tb has the same preparation protocol to attach it to the bioconjugate, and very similar biochemistry and metabolism, as 177Lu (an isotope of lutetium), one of the newest, commercially available radioisotopes for treatment. It also has similar βemissions to 177Lu, but emits more low-energy (Auger) electrons, which mean it would be more effective for treating tumours of a small size. 177Lu is already in use in several European countries, a well as Australia, Brazil and others, which should smooth the way for 161Tb.

"The development of new, better targeted, bioconjugates should be coupled with radioisotopes that have more targeted (ie short-range) radiation. The ultimate treatment would be Auger electron emitters, that would just destroy the cancer cell without harming neighbouring cells," says Dr Ulli Köster, physicist at ILL. "Doctors and regulators are understandably cautious when it comes to new therapies. 161Tb has the advantage of combining β radiation (whose effects are well-known) with additional Auger electron emission. The fact that 161Tb also has very similar in vivo behaviour to 177Lu, and is prepared and handled in the same manner, will be reassuring for the medical professionals, and so should pave the way for Auger electron therapy."

"We strongly embrace increasing the choice of available radioisotopes. We would like to use 161Tb, the first samples of which were produced by ILL and PSI, in clinical therapy. We are very delighted about this progress in basic research that will yield a direct outcome for cancer therapy," says Prof Richard Baum, Head of the Clinics for Nuclear Medicine / PET-Center, Zentralklinik Bad Berka GmbH.

The future

ILL is developing technical plans for an automated irradiation system to routinely produce 161Tb, 177Lu and other innovative radioisotopes for medical use. If financial backing is found and regulatory approval is obtained the system would become operational in 2013.

Prof Andrew Harrison, Science Director of ILL: "ILL's intense neutron flux - among the three most intense research reactors worldwide - means we are one of few places in the world with the capability to produce high quality isotopes for radiotherapy research and development. The proposed irradiation system is outside of ILL's normal sphere of activity, but we have a moral imperative to do this work. It's a great example of how a publicly funded facility can have a totally unexpected and unpredictable payoff for society."

Notes

1. Different types of radiation are emitted by radioisotopes and used for medical applications:

a. Beta radiation has a range of few mm to cm and can damage or destroy cells in this range

b. Auger electrons have a range of few micrometers only, shorter than a cell's diameter. Their damaging effect is confined to a single cell, or even part of it. To be most effective Auger electron emitters need to be coupled to 'internalising' bioconjugates that are selectively incorporated into cancer cells

c. Gamma radiation has a long range and will mainly escape the patient's body. It can be detected with gamma cameras so is useful for monitoring exactly where in the patient's body the radioisotope has been delivered

2. Bioconjugates - Vehicles like peptides, antibodies etc that selectively deliver the radioisotope to the cancer cells.

3. Preparation protocols for radioisotope therapies - Radioisotopes are delivered to hospitals, where radiopharmacists attach the radioisotopes to the bioconjugate. The combined radiopharmaceutical is then injected into the patient. The chemical similarity of 161Tb and 177 Lu means that the radiopharmacists can do a straight substitution, they do not have to develop a new preparation protocol.

Source:
Institut Laue-Langevin (ILL)
Paul Scherrer Institute
Zentralklinik Bad Berka