| Summary: | Nuclear imaging has the ability to non-invasively probe target expression, drug pharmacokinetics, and monitor treatment response. With many cancer therapies inducing DNA damage to overwhelm tumour cells into arrest, there has been a push to investigate the DNA damage response with regards to understanding the key proteins involved and the development of DDR inhibitors to enhance current DNA damaging therapies. The use of DDR inhibitor radiotracers with PET or SPECT could allow scientists to quickly collect information on tumour phenotype, DDRi drug interactions and pharmacokinetics, calculate levels of DNA damage as a result of previous therapies, and could ultimately improve patient stratification. With some key targets of the DDR such as γH2AX and PARP, already under investigation for nuclear imaging, this thesis aimed to investigate ATM as a potential new target for DDR nuclear imaging, as well as expanding the selection of PARPi radiotracers to allow imaging of tumours in the brain. This body of work highlights the key challenges faced in the chemistry and radiochemistry of developing new radiotracers and demonstrates the limitations of ATM as an imaging target. It is the hope that this research will pave the way for further development of ATMi radiotracers to verify whether ATM is a suitable molecular imaging target and to promote the development of BBB-penetrable PARPi tracers.
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