Terbium: A new 'Swiss Army knife' for cancer diagnosis and treatment

December 24, 2012

A collaboration between the Paul Scherrer Institute, CERN's ISOLDE facility, and the Institut Laue-Langevin, has published preclinical study results for a newly developed set of tumour-targeting radiopharmaceuticals. The results, published in The Journal of Nuclear Medicine, are a significant success for this group of nuclear medicine specialists and radiochemists, demonstrating the potential to provide a new generation of radioisotopes with excellent properties for the diagnosis and treatment of cancer.

'Receptor-targeted' radiopharmaceuticals consist of a which is attached to a carrier that selectively delivers it to tumour cells. They are used in two ways.

• Nuclear medical imaging - involves injecting a positron or gamma-ray-emitting radiopharmaceutical into the bloodstream as a marker. Once bound to the (e.g. a tumour), the gamma-ray emissions of the radioisotope or the positron annihilation allow diagnosis and possibly the determination of the severity of a variety of diseases, including many types of cancers.

• Targeted radionuclide therapy – makes use of short-range particle-emitting radioisotopes with the ability to destroy tumour cells.

Traditional radioisotopes (such as and yttrium-90), employed in the first generation of radiopharmaceuticals do not offer ideal nuclear properties for all therapeutic applications. As a result more recent developments of radiopharmaceuticals make use of emerging radioisotopes with more favourable decay properties such as lutetium-177, which reduces both to healthy tissue and the need to isolate the patient during treatment.

The ideal situation would be to select the most suitable radioisotopes at an early stage in drug development, allowing an overall optimization of the radiopharmaceutical. However, such innovative radioisotopes are often not commercially available and dedicated production methods are often lacking.

Recently a method for large-scale production of one such new generation radioisotope, terbium-161, has been developed by radiochemists from TU Munich and PSI Villigen working with samples irradiated at the ILL in Grenoble and at FRM2. They were successful in supplying this isotope in the quality and quantity needed for clinical applications.

In this latest study terbium-161 has been complemented by three other terbium isotopes, produced by high-energy proton-induced reactions at ISOLDE-CERN, which together have the potential to both diagnose and treat cancer. Having so-called 'matched pairs' of isotopes (based on the same chemical element) is particularly valuable and opens up the opportunity for personalised, patient-specific treatment to increase efficiency and reduce side effects.

Terbium (Tb) is the only element in the periodic table offering not only a matched pair but four clinically interesting radioisotopes with complementary nuclear decay characteristics which between them could be used in the full range of procedures in nuclear medicine. Thus, terbium can serve as the "Swiss Army knife of Nuclear Medicine", for fundamental studies of new radiopharmaceuticals and for detailed comparisons of targeted therapy options.

The trials

In a new joint article, scientists from the PSI, ILL and CERN reported on the first comprehensive preclinical study of this new range of terbium radiopharmaceuticals. The were combined with a newly developed delivery agent called 'cm09' and then administered to tumour-bearing mice. For the imaging isotopes, the scientists applied two common diagnostic techniques to study its uptake by cancer cells. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) were applied to the mice 24 hours after the injection of terbium-152, terbium-155 and terbium-161 respectively. Terbium-161 and terbium-149 were investigated with regard to their therapeutic efficacy by comparing tumour growth and survival rates in the mice under treatment with an untreated control group.

Key findings

• PET/CT and SPECT/CT studies using both diagnostic isotopes terbium-152 and terbium-155 and the gamma-emitting therapeutic isotope terbium-161 provided excellent tumour visualization 24 hours after injection

• Both therapeutic isotopes provided a significant inhibition to tumour growth in mice, resulting in a marked delay in tumour growth or even complete remission. In particular therapy with terbium-161 resulted in complete remission in 80% of cases.

The performance of terbium-161 was particularly encouraging as previous work by TUM, PSI and the ILL, published in 2011, demonstrated that this isotope could be produced in the quantity and quality required for clinical routine application.

Prof. Cristina Müller (PSI) said: "In this study, we designed new diagnostic and therapeutic radiopharmaceuticals by combining the vitamin folic acid as a tumor-targeting agent and four different isotopes that have unique nuclear properties for different applications in . Excellent results were obtained in tumor-bearing mice which raise hopes for future development of such radiopharmaceuticals for clinical use in cancer patients".

Explore further: Radionuclide treatment against small tumors and metastases

More information: Journal of Nuclear Medicine, 2012 53:1951-1959, jnm.snmjournals.org/content/53/12/1951.abstract

Related Stories

Radionuclide treatment against small tumors and metastases

June 16, 2011
Medicine could very soon have a new ally in the fight against cancer: Terbium-161. Its most important weapon: Conversion and Auger electrons. Researchers at the Technische Universitaet Muenchen have developed a new treatment ...

New radioisotope will improve cancer therapy

April 22, 2011
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 ...

State-of-the-art scanning detects more cancer in bone

June 11, 2012
Research revealed at the Society of Nuclear Medicine's 2012 Annual Meeting describes new approaches to imaging for the detection of tumors in complex cases of bone cancer. Hybrid imaging technology combining computed tomography ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.