[18F] FDOPA PET Imaging in Glioma: Feasibility Study for PET Guided Brain Biopsy

\[18F\]fluorodopa (3, 4-dihydroxy-6-\[18F\]fluoro-L-phenylalanine/ FDOPA) is an amino acid PET tracer originally developed for brain imaging in patients with movement disorders but has been found to be useful in brain tumour imaging. \[18F\]fluorodopa has been demonstrated to be predominantly transported by the L-type amino acid transporter without significant uptake into surrounding normal brain parenchyma with the exception of the basal ganglia. Assessing the feasibility of performing PET guided histopathology in a single and multi-site setting will be crucial in order to use PET as a planning tool for brain biopsy to detect high-grade transformation in low-grade gliomas.

Glioma is a cancer of unmet need, where survival trends have not significantly changed for decades. The distinction between high-grade (HGG) and low-grade glioma (LGG) is important as both entities confer different prognoses and management strategies. This distinction is normally made on biopsy sampling and conventional imaging. However, sampling errors are not uncommon due to the heterogeneous nature of glioma. Case series have described under-grading of gliomas on biopsy in 28% to 63% of cases. Furthermore, up to one third of high-grade gliomas may not display the typical imaging characteristics (enhancement) of a high-grade glioma. Therefore, more accurate imaging may help to make this distinction and guide biopsy and clinical management decisions at the outset. There has been growing interest in the use of amino acid PET in glioma imaging. Transport of amino acids across the blood brain barrier and low physiological levels of tracer uptake within the brain allow for good tumour visualisation. The most frequently used amino acid PET tracers described in clinical literature are \[11C\]methionine, \[18F\]fluoroethyltyrosine and \[18F\]fluorodopa, which predominantly reflect leucine transport, being mainly transported by LAT1, a high affinity leucine transporter. Alongside depiction of tumour volume, described roles of amino acid PET include differentiation of true disease progression from pseudo progression, detection of residual disease in the post-surgical patient, biopsy guidance and prognostication. Rationale The primary objective of the study will be to establish the feasibility of performing \[18F\]fluorodopa PET guided histopathology in a single and multi-site setting. Basic tumour characterisation (for example Ki67 expression and detection of IDH mutations) will be undertaken.