Project description

In 2007, 12 million new cases of cancer have been diagnosed and 7.5 million people died from the disease worldwide. These numbers are expected to increase progressively as the population is ageing. At present cancer is the second most common cause of death and if this trend continues by 2050 there will be worldwide 17.5 million deaths and 27 million new cases annually. Clearly, this tendency needs to be stopped not only by introducing new innovative methods, but also by educating new generations of scientists in fields directly related to cancer prevention, diagnostics, treatment and management (the health care cycle).

The aim of the project is to provide multi-disciplinary high-quality training to young researchers, to become highly skilled in health-related topics. In addition, they will acquire the key expertise essential to become the future pioneers in their field thanks to the associated professionals which are strategic partners within the present consortium. The fellows will be educated in several fields including: nuclear imaging, soft matter, and nuclear-, organic-, polymer- and radiopharmaceutical chemistry. In addition, the project will offer the fellows a broad knowledge on nuclear molecular imaging and radionuclide therapy. Regarding nuclear molecular imaging, we will mainly focus on the application of the following techniques: Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET). An in-depth, multidisciplinary training will combine the development of molecular and supramolecular carriers for diagnosis and treatment of cancer and their pre-clinical evaluation, with educational visits and courses. Special emphasis will be made on radionuclide therapy, including the novel alpha particles-based radionuclide therapy.

The research objectives of the proposal are: production of radionuclides with the most appropriate properties for molecular imaging and/or radionuclide therapy, their incorporation in newly designed molecular and supramolecular carriers and finally their pre-clinical evaluation and comparison. Radiotherapeutic evaluation will be limited to neuroendocrine tumours and preclinical tumour models thereof, due to the extensive experience of the medical partner in the treatment of this tumour type.

The project as such is expected to deliver, pre-clinically evaluate and compare three categories of carriers. The first category will consist of supramolecular carriers, made from commercially available block copolymers and will be radiolabelled with PET radionuclides from generators or reactor produced radionuclides. The second category will consist of supramolecular carriers made from chemically modified block copolymers to include a metal complexation group and/or targeting agent. Before or after self-assembly, these carriers will be labelled in a similar way to the first category. The third category will consist of radiolabled molecular carriers composed of a chelator, a tumour targeting agent and a molecular probe or therapeutic entity. All of these categories will be tested and compared first in vitro and subsequently in vivo.

The most appropriate approach to reach these scientific and training objectives is to integrate all the necessary research pieces (i.e. radionuclide production, radiolabelling, pre-clinical evaluation etc.) into five interconnected subprograms:

1.      Development of new production routes for radionuclides and radionuclide generators

2.       Development of chelators molecules and linking strategies to molecular carriers and block copolymers

3.       Optimization of supramolecular carriers and in vitro internalization evaluation

4.       Developing of radiolabelling approaches of molecular and supramolecular carriers and PET imaging

5.     Testing the therapeutic and diagnostic potential of molecular and supramolecular carriers in vivo

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