A non-randomised study investigating the use of multi-parametric magnetic resonance imaging (mpMRI) to develop imaging biomarkers that will be used to escalate dose to subregions of tumour that are resistant to radiation therapy

All participants will be recruited after diagnosis of localised prostate cancer and before commencing any treatment, including prostatectomy, radiation therapy, or androgen deprivation therapy. Standard clinical management will proceed according to the treating team and will not be influenced by the study results. All participants will undergo research-specific MRI scans in addition to standard of care imaging. All participants will undergo MRI safety screening in accordance with local clinical policy prior to study imaging. This feasibility study is designed in two stages: Stage 1 (6 participants): Participants will receive research-specific MRI scans only. Stage 2 (25 participants): Participants will receive research-specific MRI scans. Their archived diagnostic biopsy tissue samples will be collected and analysed. Stage 2 will commence immediately after the completion of Stage 1. Participants from Stage 1 are not able to participate in Stage 2. MRI scans (all participants) – Multi-parametric MRI is the use of several MRI techniques to provide complimentary information about the structure and the biological characteristics of tissue. This study will use multi-parametric techniques, that are not used in standard-of-care MRI, to provide additional information on tissue composition, function, metabolism and oxygenation. As total imaging time is like to be >1 hour, participants will undergo two research-specific MRI scan sessions. The two sessions may be performed on the same day or up to 7 days apart (note this is subject to scanner and participant availability, exact timing cannot be pre-specified) and must be completed after diagnostic biopsy and before any prostate cancer treatment is initiated. MRI scanning will be performed on a 3 Tesla MRI scanner by suitably qualified MRI radiographers according to the study MRI acquisition guidelines. The second MRI session will include administration of the standard clinical dose of the gadolinium-based contrast agent gadobutrol (Gadovist®, Bayer, Germany). An intravenous cannula will be inserted by trained staff and used for contrast administration at a standard clinical dose of 0.1 mL/kg body weight (equivalent to 0.1 mmol/kg). Injection will be performed by a power injector to obtain a constant injection rate and will be timed by the radiographer to occur just after the DCE-MRI acquisition is started. The MRI scans will be performed in the supine position, and each session will take up to one hour including setup time. Participants will be asked to remain still throughout the scans. Diagnostic biopsy tissue collection and analysis (participants recruited to Stage 2 only) – No additional biopsy procedures will be performed. Archived prostate biopsy tissue samples remaining after completion of standard diagnostic assessments will be collected upon recruitment, together with the diagnostic MRI and ultrasound images used during the biopsy procedure. The tissue samples will undergo research-specific molecular analyses for biomarkers of tumour hypoxia. These analyses are not part of standard clinical care and will be used to validate and correlate the MRI findings with tissue-based measures of hypoxia. Prostate cancer treatment and all clinical management decisions will remain standard of care and will not be affected by the MRI or molecular biomarker results. The imaging and tissue analysis data will be used solely for research purposes to develop and validate MRI methods for identifying hypoxia in prostate cancer.