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Novel radionuclides to kill cancer

28 October 2015

A new radiolabelled molecule obtained by the association of a 177Lu isotope and a somatostatin-analogue peptide is showing potential as a cancer killer for certain types of tumour. It is being developed by Advanced Accelerator Applications (AAA), a radiopharmaceutical company that was set up in 2002 by Stefano Buono, a former CERN scientist. With its roots in the nuclear-physics expertise acquired at CERN, AAA started its commercial activity with the production of radiotracers for medical imaging. The successful commercial activity made it possible for AAA to invest in nuclear research to produce innovative radiopharmaceuticals.

177Lu emits both a β particle, which can kill cancerous cells, and a γ ray, which can be useful for SPECT (Single-Photon Emission Computed Tomography) imaging. Advanced neuroendocrine tumours can be inoperable, and for many patients there are no therapeutic options. However, about 80% of all neuroendocrine tumours overexpress somatostatin receptors, and the radiolabelled molecule is able to selectively target those receptors. The new radiopharmaceutical acts by releasing the high-energy electrons after internalization in the tumour cells through the receptors. The tumour cells are destroyed by the radiation, and the drug is rapidly cleared from the body via urine. A complete treatment consists of only four injections, one every six to eight weeks.

The radiolabelled molecule is currently being used for the treatment of all neuroendocrine tumours on compassionate-use and named-patient basis in 10 European countries, and is seeking approval in both the EU and the US. A phase-III clinical trial (the NETTER-1 clinical study) conducted in 51 clinical centres in the US and Europe, is testing the product in patients with inoperable, progressive, somatostatin-receptor-positive, mid-gut neuroendocrine tumours. The results of this trial were presented on 27 September in a prestigious Presidential Session at the European Cancer Congress in Vienna, Austria. The NETTER-1 trial demonstrated that there is a statistically significant and clinically meaningful increase in progression-free survival in patients treated with the radiolabelled molecule, compared with patients treated under the current standard of care. The median progression-free survival (PFS) was not reached during the duration of the trial in the Lutathera arm and was 8.4 months in the comparative group (p < 0.0001, hazard ratio: 0.21).

Another labelling radionuclide, the 68Ga positron emitter, is a good candidate in the production of a novel radiotracer to be used in the precise diagnosis and follow-up of the family of diseases using PET (positron emission tomography).

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