RADIOBIOLOGICAL AND COMPUTATIONAL EVALUATION OF THE AUGER ELECTRON EMITTERS, 67GA AND 111IN, FOR MOLECULAR RADIONUCLIDE THERAPY

Dr Lefteris Livieratos is a Senior Lecturer at KCL, a Clinical Scientist (Medical Physicist) in Nuclear Medicine at Guy's & St Thomas' Hospitals and has successfully supervised two PhD students (for one of which joining as supervisor after year 1). His research focuses on image quantification methodology for clinical translation of new radiopharmaceuticals. He has over 15 years' experience in PET/CT, SPECT/CT and targeted radionuclide therapies, including clinical implementation of novel therapies (recently, 90Y- and 177Lu-DOTATATE for neuroendocrine tumours and 223Ra for bone-metastasised prostate cancer). He currently holds a five-year NIHR/HEFCE Senior Clinical Lectureship (2013-2018) focusing on radionuclide therapy. Dr Livieratos will lead on dosimetry and provide Medical Physics Expert support.
Dr Terry is a Lecturer in Radiobiology at KCL and is an expert in studying biological effects of therapeutic radionuclides (mainly Auger electron emitters and external beam) in cells and tissues and has extensive experience in molecular radionuclide imaging with peptides and antibodies. She also has expertise in monitoring therapy response by imaging after radiotherapy. She will oversee the biological studies which will provide input to computational modelling and model verification.
Some preliminary work (Livieratos) from a previous PhD project (completed 2015) utilised small-scale radiopharmaceutical distributions from micro-autoradiography with I-131 and Re-188 to develop a computational model for dose distributions within the thyroid in order to assess absorbed doses in thyroid follicular cells and in thyroid colloids. Such data, together with small animal in vivo data with SPECT and PET have contributed to the microscopic and macroscopic dosimetric profile of Re-188 as a potential clinical agent for the treatment of thyroid disease. This work was based on the MCNPx platform for Monte Carlo simulations of emission with energies higher than 10 keV.
Earlier work by Jordan Cheng, in conjunction with Dr. Verger (postdoc, Terry Group), has also provided useful insights into the therapeutic potential of 67Ga with a cell-free plasmid assay. Overall, it was found that 67GaCl3 induced greater plasmid damage than 111InCl3, providing further evidence suggesting higher energy possessed by the released Auger electrons of 67Ga and potentially higher cytotoxicity than 111In. Plasmid damage by external beam radiotherapy (EBRT) also provided interesting insights into plasmid DNA damage kinetics, with the data enabling mathematical modelling by our collaborator (Dr. Daniel Burnham, Francis Crick Institute). Higher plasmid concentrations (1.25 ng/L vs. 5 ng/L) surprisingly offered protection of DNA from EBRT treatment, despite the lack of any repair enzymes, and resulted in reduced plasmid conformational switch rates.