Introduction to the

AD-4 (ACE) Collaboration at CERN

Antiprotons may help fight cancer

A pioneering experiment at CERN with potential for cancer therapy has produced its first results. Exploiting the unique capability of CERN's Antiproton Decelerator to produce a narrow monoenergetic antiproton beam at the right energy, the Antiproton Cell Experiment (ACE) has shown that antiprotons are much more effective than protons for neutralizing cancer cells by irradiation. Cancer therapy is about collateral damage: destroying the tumour while avoiding damage to healthy tissue. Unwanted exposure of healthy tissue can cause side effects, result in reduced quality of life and is believed to increase the risk of development of secondary cancers. Compared to a proton beam, an antiproton beam causes four times less cell death in the healthy tissue for the same amount of cell deactivation in the cancer.

Michael Holzscheiter, ACE spokesperson (left), retrieves an experimental sample after irradiation with antiprotons, while Niels Bassler (centre) and Helge Knudsen from the University of Aarhus look on.

Dose deposition

In contrast to the widely used photon therapy, in hadron therapy, which began in 1946 with Robert Wilson's seminal paper, "Radiological Use of Fast Protons", the irradiation of healthy tissue by the heavy charged particles (hadrons) is much reduced because most of their energy is deposited at the end of the flight path of the particles – the Bragg peak – with little deposited before and beyond . However, the question remains how to maximize the concentration of energy onto the tumour. The first speculations that antiprotons could offer a further significant gain in targeting tumours through the extra energy released by annihilation date back more than 20 years (Gray and Kalogeropoulos 1984). Now the ACE collaboration has tested this idea by directly comparing the effectiveness of cell irradiation using protons and antiprotons.

Physical dose deposition by X-rays, protons and antiprotons, as calculated using the Monte Carlo simulation code FLUKA, clearly demonstrates the reduction of dose outside the target area for protons and antiprotons compared with X-rays.

To simulate a cross-section of tissue inside a body, the experiment uses tubes filled with live hamster cancer cells suspended in gelatine. These are irradiated with beams of protons or antiprotons at a variety of intensities and various energies giving them about a 2 - 10 cm range in water. After irradiation the gelatine is extruded from the tubes and cut into 1 mm slices. These are then dissolved in growth medium and the cells are placed in Petri dishes in an incubator. After a few days the naked eye can see that some of the cells have produced healthy offspring. This gives a measure of the survival of cells ( i.e. their ability to multiply) along the beam path for the different dose levels. Cell survival is plotted for the entrance and the Bragg-peak regions as a function of particle fluencies, and the ratio of dose for a 20% survival in these two regions is extracted.

Cell inactivation

Comparing beams of protons and antiprotons that cause identical damage at the entrance to the target, the results of the experiment show that the damage to cells inflicted at the end of the beam is four times higher for antiprotons (Holzscheiter et al. 2006) The method directly samples the total effect of the beams on the cells, combining the enhanced energy deposition in the vicinity of the annihilation point and the higher biological effectiveness of this extra energy (delivered by nuclear fragments). The experiment demonstrates a significant reduction of the damage to the healthy cells along the entrance channel of a beam for antiprotons compared with protons

In [a] is shown schematically the amount of cell-inactivation for antiprotons, protons and X-rays, for the same cell damage to healthy tissue in the entrance channel. The irradiated part of a body could be the head, with the brain containing a tumor [b]. In [c] is shown the distribution of dose for an antiproton beam, illustration its ability to deposit dose inside the body with only little damage to the surrounding tissue.

While antiprotons may seem unlikely candidates for cancer therapy, the initial results from ACE indicate that these antimatter particles could lead to more effective radiation therapy. There is no doubt, however, that the first clinical application is still at least a decade away.

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Antiprotons may help fight cancer

Dose deposition

Cell inactivation

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