Periodic Reporting for period 3 - HYPERDIAMOND (The Diamond Revolution in Hyperpolarized MR Imaging – Novel Platform and Nanoparticle Targeted Probe)
Periodo di rendicontazione: 2019-01-01 al 2020-06-30
Technologies for imagining non-invasively small numbers of molecular probes to help elucidate particular targets or pathways in vivo is currently undergoing a technological revolution. Recent breakthroughs in molecular hyperpolarization (HP) proved > 10,000-fold increase in sensitivity on conventional magnetic resonance imaging (MRI) systems, thus providing insight into previously unseen metabolic processes with enormous potential for socioeconomic relevant diseases ranging from cancer to heart disease. Pyruvate-based HP imaging for example was clinically demonstrated to be effective for prostate cancer diagnostics in human patients. However, the current state-of-the-art HP methods are expensive and cumbersome, limiting the access to HP technology, and require long HP times of 60-90 minutes per dosage; HP probes exhibit short HP duration (1-5 minutes), limiting the usage of HP to metabolic imaging. A quantum technological breakthrough, nitrogen-vacancy defects (NV centres) in diamonds, is set to revolutionize the field of HP for both hyperpolarizer and probes.
A crucial new MRI contrast agent are functionalized NDs. HYPERDIAMOND has established high-yield high pressure high temperature synthesis methods of diamond particles with different amounts of 13C ranging from 5% to 37% and have scaled them up to the gram regime. The best reagents for removing 100% of amorphous carbon and graphite from the ND surface to prepare them for functionalisation were identified. Well adapted to this, the surface chemistry for NDs including ultrafast, second time scale, functionalization was developed to enable their use as targeted hyperpolarized-MRI probes. Cellular uptake and biocompatibility of coated fluorescent NDs were established and, as a result, stable bioactive surface coatings are now available and can be customized for the needs of the medical partners.
The synthesis, formulation and characterisation of molecular imaging probes has been put in place. These metabolic probes have been HP with the HyperSense dDNP polarizer and applied to biological systems related to cancer to assess their utility for cancer imaging. The biological systems that have been developed in relation to cancer consist of active oncogenic enzymes (in vitro systems), perfused tissues, such as breast cancer tumors and hepatocellular carcinoma that are kept viable for several hours (ex vivo systems).
The HYPERDIAMOND team was also able to prove the use of PET/MRI for longitudinal monitoring of the in vivo biodistribution of NDs in native and tumor-bearing mice. To this end, the surface of the NDs were functionalized with a chelator for enabling linkage of 68Ga and 89Zr for PET imaging. Accumulation of the labelled NDs was quantified by PET while MRI provided high-resolution anatomical details for determination of the anatomic structures showing accumulation. All required methods for performing the in vivo validation on HP NDs have been successfully established in the project.
Three SMEs have participated in the HYPERDIAMOND project, NVision Imaging Technologies GmbH (production of the Diamond Hyperpolarizer), Van Moppes (ND production), and Lapuntuh/KanFit (Production of custom made permanent magnets). In order to support the path towards commercialization, HYPERDIAMOND established a roadmap for the regulatory process of the Diamond Hyperpolarizer, and performed a market analysis, including market size estimation, customer segmentation, main potential clinical applications and advantages over incumbent technologies.
The Diamond Hyperpolarizer and the ND probe on the basis of functionalized nanoparticles will serve both research and clinical usage that will radically improve the established pyruvate-based metabolic MRI. The fully functional prototype will be the basis of future commercialization of the technology for introducing low-cost, widely accessible metabolic imaging capabilities worldwide.