Quo Vadis Radiotherapy: Age of Hadrons.

Cancer has a major impact on the Australian community. At current incidence rates, one in three men and one in four women in Australia will be diagnosed with cancer by the age of 75. Cancer control is a national health priority area and is estimated to be the leading cause of the burden of disease in Australia in 2010, accounting for 19% of the total burden.  Radiotherapy's contribution to the fight against cancer is significant. The impact of radiotherapy in cancer survival has been estimated at 40%, compared to 49% of patients being cured by surgery and 11% of patients for systemic treatments.

A key advantage of radiation oncology is that it is an effective and non-invasive anti-cancer treatment without any associated mortality risk. However, despite the latest technological advances in radiotherapy, cancer control is still challenging for several tumour sites. The survival rates for the most deadly cancers, such as ovarian and pancreatic, have not changed over the last decades.

The solution to the problem lies in the change of focus: A) move from photons to hadrons and B) from local treatment to systemic therapy.

A)    Protons and heavy ion particles (i.e. hadrons) are considered to be ideal particles for use in external beam radiotherapy due to superior properties of the dose distribution, known as Bragg peak, that results in higher and more conformal dose to the tumour while the dose to healthy tissues is much less as compared to traditional X-ray/photon radiation. Currently, there is a strong trend internationally for the installation of proton and heavy ion treatment facilities. Australia is at the stage of adopting this technology in near future; with several exciting projects underway.  

B)    While accelerator produced hadron beams are excellent at treatment of local disease, different approach is required to target metastases and circulating cancer cells. Radio-immunotherapy is an approach where cancer cells are targeted by vectors labelled with a radioisotope. In a specific case of targeted alpha therapy (TAT), a tumour-specific antibody or protein is radiolabelled with an alpha-emitting radionuclide, termed a radioimmunconjugate (RIC) that attaches preferentially to tumour-specific antigens, produced in tumour cells, and releases high-linear energy transfer (LET) alpha particles with kinetic energy of a few MeV, resulting in localized but significant ionization damage (e.g. to DNA).

In our work, an autoradiography imaging study of TAT with Timepix detector was performed to record individual alpha particles emitted from Lewis Lung carcinoma tumour sections grown in mice that were treated with Th-227 labelled RIC and with/without chemotherapy. The alpha particle, photon, electron and muon tracks were recorded by Timepix in tumour section images. The results showed that the uptake of the RIC was four times greater when using chemotherapy prior to treatment with Th-227 labelled RIC.