Developing A Novel Theranostic Nano-Platform For Simultaneous Multimodal Imaging And Radionuclide Therapy

Abstract

The aim of this project was to develop and evaluate a theranostic nano-platform to enable Radionuclide Therapy (RNT) and multimodal imaging to improve the therapy and diagnosis of lymph node metastases. The work presented in this thesis consists of four main studies. First, Feraheme (FH) and two other superparamagnetic iron-oxide nanoparticles (SPIONs) were radiolabelled with radioisotopes commonly used in the clinic (89Zr, 177Lu and 90Y) for imaging and therapy utilising a novel chelate-free technique, which produced a high radiochemical yield and purity (up to 98%). FH nanoparticles were successfully radiolabelled with 90Y and 177Lu which was the first experimental demonstration that the HIR technique can be extended to radiolabel FH with these isotopes. In the second study, a series of phantom experiments were performed and results demonstrated that 89Zr-FH is a novel nanotechnology for simultaneous PET/MR imaging providing the capability of integrating the spatial resolution and tissue contrast provided by MR imaging with the high sensitivity of PET. An additional phantom study demonstrated the ability to image 177Lu-FH using Single Photon Emission Computed Tomography. The third study was a proof of concept for 90Y RNT. Results revealed that in RNT, the kinetics of DNA double strand break (DSB) induction, repair and misrepair must be considered when deriving radiobiological parameters. The fourth study, a Monte Carlo simulation study, was performed to study the subcellular mechanisms of dose delivery of the radionuclide 223Ra when treating metastases. These simulations showed that indirect cell damage may play an important role in RNT with alpha emitters due to the stochastic nature of alpha particle energy deposition. In conclusion, these results open a pathway towards a novel nuclear nanoplatform for multimodal imaging and RNT of lymph node metastases.