P01.119 TSPO imaging in High Grade Glioma - a multitracer PET, MRI and neuropathology study

The translocator protein (TSPO) is an 18 kDa mitochondrial molecule (previously known as Peripheral Benzodiazepine Receptor), largely studied in neuroinflammation disorders and recently of growing interest in neuro-oncology [2,3]. The aim of our study is to investigate the uptake of [11C](R)-PK11195 (a PET radiotracer for TSPO) and [11C]Methionine and correlate with MR Imaging. Eleven patients (mean age 60 ± 16, M/F=5/6) with lesions suspicious of HGG on clinical MRI were recruited. All patients underwent contrast-enhanced structural and diffusion tensor MR imaging as well as dynamic [11C]-(R)PK11195 and [11C]Methionine PET scans before treatment. Parametric maps of [11C]-(R)PK11195 binding potential (BP) were generated using simplified reference tissue modelling with cerebellar grey matter as reference tissue. BP parametric maps were co-registered to post-contrast T1, fractional anisotropy(FA) and apparent diffusion coefficient (ADC) maps, and finally to [11C]Methionine summed image. Tumour was delineated as a T/N threshold above 1.4 on co-registered [11C]Methionine PET scans and a further regions delineating gadolinium enhancement and necrosis within the tumour were manually delineated. Co-registered MR/PET images were used to guide targeted tumour biopsies which were used to compare directly with histology. All confirmed HGG patients demonstrated a vivid uptake of [11C](R)-PK11195 (mean BP of whole tumour delineated using 1.4 [11C]Methionine threshold: 2.95 range 1.7–4.1; maximal BP: 4.12 range 2.1–6.2). [11C]Methionine uptake extended beyond gadolinium enhancement almost in all HGG cases, and regions of higher uptake did not spatially correlate to hottest [11C](R)-PK11195 areas (Figure 1). A significant correlation was found instead between increased [11C]Methionine uptake and mean diffusivity values (pairwise correlation coeficient = 0.69, p<0.01). TSPO antibody stain of hot TSPO targeted biopsies showed clearly higher values on optical density(OD) measurements, compared to cold uptake targeted areas within the tumour, confirming the correlation of [11C](R)-PK11195 PET imaging and histology (hot biopsies mean OD 4.3% vs 1.3% cold, p<0.001) (Figure 2). Further 3D histology modelling, colouring with multiple antibodies (Iba1, IDH1 and CD31) showed the localisation of TSPO in tumour hottest regions is mainly in the neoplastic cells rather than microglia or endothelium. Tumour recurrence was found to coincide with the regions of higher [11C](R)-PK11195 uptake in 2 of the patient's clinical MR scans. [11C]-(R)PK11195 has the potential to detect early recurrence and provides information complimentary to perfusion metrics in early detection of recurrence. Methionine offers a better tumour delineation which could lead to more extensive surgical resections and better chances for survival.