European Commission Joint Research Centre Institute for Transuranium Elements
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Cancer is one of the main health problems of today. Unfortunately, the treatments that are currently available, even though often effective, cannot permanently cure the majority of cancers. This is typically true for cancers that have formed metastases and have spread around the body. New therapy approaches are therefore urgently needed.
Targeted Alpha Therapy (also called Alpha-Immunotherapy) is such a new approach to cancer treatment. It is based on the coupling of alpha particle emitting radioisotopes to tumour selective carrier molecules, such as monoclonal antibodies or peptides. These molecules have the ability to selectively target tumour cells even if they are spread throughout the body. They recognize the targeted cancer cells through antigens that are expressed on the cell surface and can bind selectively to these cells, similar a key fitting into a lock. In targeted alpha therapy these carrier molecules serve as vehicles to transport the radioisotopes to the cancer cells. This is called the "magic bullet" approach.
The typical radio-immunoconjugate has 3 components:
- a tumour selective carrier molecule, such as an
monoclonal antibody or a peptide
- an alpha-emitter (typically 213Bi or 225Ac)
- a chelate stably linking the two.
Radioisotopes that emit alpha particles seem particularly promising to selectively destroy cancer cells. Alpha particles have a high energy in the range of 5-9 MeV and at the same time a very short path length in human tissue below 0.1 mm, corresponding to less than 10 cell diameters. Consequently, the use of alpha emitters allows the specific targeting and killing of individual malignant cells, while minimizing the toxicity to surrounding healthy tissue. The application of alpha emitters has the greatest potential for therapy of cancers where individual cancer cells or small cell clusters need to be targeted, as in the case of leukemia, for the treatment of micro-metastases or for the treatment of residual disease after chemotherapy or surgical removal of the main tumor mass. Recently it could be demonstrated in animal studies that targeted alpha therapy can also be effective for the treatment of fungal, bacterial and viral infections, including HIV infections.
Trajectory, range and energy depositionation (ionisation density) of a beta particle (from Y-90, top), and an alpha particle (from Bi-213, bottom), superimposed on a microscopic image of cells.