Synthesis, radiolabelling and in vitro imaging of multifunctional nanoceramics

[EN] Molecular imaging has become a powerful technique in preclinical and clinical research aiming towards the diagnosis of many diseases. In this work, we address the synthetic challenges in achieving lab-scale, batch-to-batch reproducible copper-64- and gallium-68-radiolabelled metal nanoparticles (MNPs) for cellular imaging purposes. Composite NPs incorporating magnetic iron oxide cores with luminescent quantum dots were simultaneously encapsulated within a thin silica shell, yielding water-dispersible, biocompatible and luminescent NPs. Scalable surface modification protocols to attach the radioisotopes Cu (t=12.7 h) and Ga (t=68 min) in high yields are reported, and are compatible with the time frame of radiolabelling. Confocal and fluorescence lifetime imaging studies confirm the uptake of the encapsulated imaging agents and their cytoplasmic localisation in prostate cancer (PC-3) cells. Cellular viability assays show that the biocompatibility of the system is improved when the fluorophores are encapsulated within a silica shell. The functional and biocompatible SiO matrix represents an ideal platform for the incorporation of Cu and Ga radioisotopes with high radiolabelling incorporation.
The authors are grateful for the helpful contributions, discussions and training received from the following: Professors Jason Lewis, Stephen Faulkner, and Philip Blower (MSKCC New York, Oxford and London KCL, respectively) and Drs H. Betts and P. Waghorn (Oxford and Harvard, respectively). The authors would like to thank Drs Paul Burke and Patrick Riss (Wolfson Brain Imaging Centre, Addenbrooke’s Hospital, Cambridge) for provision of 64Cu and training in this facility. Dr. Adrian T. Rogers (Microscopy and Analysis Suite), Prof. Rex M. Tyrrell (Department of Pharmacy & Pharmacology at the University of Bath), Rebecca Diment (Bath), Dan Lee (Oxford), Drs Justin P. O’Byrne and Stephen E. Flower are thanked for their invaluable contribution to preliminary aspects of this work. We thank Dr Michael W. Jones (Oxford) for assistance with the acquisition of some of the fluorescence microscopy images, Professor Quentin Pankhurst (UCL) for assistance with magnetic measurements and Dr N. Rees (Oxford) for paramagnetic NMR work. Dr Petra Cameron is thanked for assistance with early-stage tests on a proof-of-principle quantum dot encapsulation. The authors thank the Royal Society, TSB, EPSRC and MRC for funding, also the EPSRC Mass Spectrometry service (Swansea). The team was also funded by the European Commission FP7 Programme through the Marie Curie Initial Training Network PROSENSE (grant no. 317420, 2012–2016) and SIP also thanks the European Commission for an ERC Consolidator Grant (O2SENSE Program 617107, 2014–2019).