Nick Fletcher

Radiobiology - Understanding the body's response to radiopharmaceuticals

Targeted radionuclide therapies are undergoing rapid growth as next-generation radiotherapeutics for multiple cancers. Targeted alpha-therapeutics (TATs) in particular are highly potent and outperform current clinical options, representing an opportunity to produce a step change in patient outcomes. Despite international research focus on developing TATs, there remains significant knowledge gaps in understanding associated biological and immunological responses which have key impacts on subsequent efficacy. I have multiple ongoing projects working to addresses this by investigating the interplay between TAT and associated localized cellular, inflammation and immune responses. These projects all fall within my research theme of radiobiology and range from assays in molecular and cellular biology, through to preclinical efficacy and molecular imaging studies to probe all aspects of this research question.

Targeted nanomedicine radiopharmaceuticals – Next generation treatments for cancer

Molecular radiotherapy (MRT) involves targeted delivery of ionising radiation to trigger localised cell death. Targeted irradiation is achieved using alpha (α) or beta (β-) emitting radionuclides that are incorporated into a radiopharmaceutical. While most MRT research to date has focused on the delivery of β--emitting radionuclides (e.g. 177Lu), growing interest has been focused on α-emitting radionuclides such as 225Ac and 212Pb. Highly ionizing α-particles deposit 100–1000 times greater energy per unit path length than the current clinical standard β- particles, which gives them the ability to produce lethal DNA double-strand breaks within the cell nucleus while reducing the amount of unwanted radiation to surrounding tissues.

Such MRT approaches require a targeting platform to delivery radiotherapeutic payloads. Recently we have demonstrated 212Pb-loaded nanomedicines with excellent efficacy in preclinical models, showing complete tumour regression in many cases. Projects in this space will work on expanding this MRT platform through optimization of materials and dosing regimens as well and producing novel targeting ligands to target a wider range of cancer types. These projects fall within my research theme of nanomedicines and radiopharmaceutical development, involving work ranging from bioengineering and polymer synthesis through to preclinical efficacy and molecular imaging studies to develop potent next-generation nanomedicine radiopharmaceuticals.