Combination of FM with US, DM, MRI and CT medical imaging techniques increases the sensitivity for BC detection of around 30-60% compared to FM. However, the clinical application of this multimodal imaging diagnosis approach is still problematic due to existing commercial contrast agents show low specificity and fails to detect non-vascularised malignant tumours.
Core-shell NPs formed by a magnetic core and shell of a radiopaque element (Au or Bi) are a promising alternative for their use of MCAs in combined MRI-US and X-ray imaging diagnosis, because their high biocompatibility, contrast efficacy and long-term colloidal stability. However, the use of these material is problematic due to: 1) The X-ray attenuation coefficients of Au and Bi limits their use only to high energy CT examinations. 2) Conventional chemical procedures used to synthesize these NPs fail to be transferred from the laboratory to the industry, because they involve numerous parameters difficult to control.
In this state of development of the project, we have achieved: 1) the development and optimization of a laser ablation in liquids process to produce a wide range of multimodal NPs, without the use of high expensive and toxic chemical precursors and surfactants. 2) Synthesis of a new generation of novel multimodal NPs showing contrast in MRI and X-ray imaging. 3) Confirmation that these nanoparticles are not toxic by performing in vitro cell viability assays in HeLa cells.
This proposal pursues the development of new synthesis methods and products for the industry of medical imaging contrast agents. With a global market of $6.2 billion in 2012, it consists mainly in medium size companies, which dedicate limited efforts to product developing due to it takes excessive time and high cost to fabricate new contrast agents (10 years to develop and a cost of $150 million). Thus, in the long term, the successful industrial transfer of the laser driven synthesis process proposed in this project, which allows high production of a broad variety of contrast agents, could position to the European companies, which will opt in the future for this technology, to the head of this industrial area. Moreover, the in vivo validation and clinical application of the multimodal contrast agents proposed in this research will improve breast cancer diagnosis, allowing a selection of patients without the need of a biopsy. In this context, it is important to note that, this research will be continue through a research project of the Spanish Government (MA2015-67354-R), which is focused on the conjugation of these multimodal contrast agents with Trastuzumab (Anti-HER2 antibodies) to obtain anti-HER2-NPS targeted toward breast tumours with HER2 overexpression; the in vivo validation of the biocompatibility and the ability of these anti-HER2-NPs conjugates to generate contrast in US, MRI and X-ray imaging techniques and detect Bc-HER2+ tumours; and 3) The implementation of a proof of concept laser ablation in liquids synthesis reactor to promote their application in production plants of the imaging contrast agents industry.
