P04.01 [11C]-(R)PK11195 PET imaging and Dynamic MRI in Transforming Gliomas

Abstract

INTRODUCTION: The diagnosis of transforming glioma can be challenging with conventional MRI. Stereotactic biopsies based on post-contrast MRI can miss the regions of early transformation, therefore leading to inaccurate tumour grade. Dynamic MRI together with positron emission tomography (PET) can provide additional physiological and biological information to identify regions of anaplastic transformation. The translocator protein (TSPO) is an 18 kDa mitochondrial molecule that can be imaged with PET using the radiotracer [11C]-(R)PK11195. We compared [11C]-(R)PK11195 PET to relative cerebral blood volume (rCBV), which is known to rise earlier than contrast enhancement during progression. METHODS: Twenty-six patients (mean age 38 ± 11.5, M/F=16/10) with lesions suspicious of transforming glioma on clinical MRI were recruited. All patients underwent perfusion MRI and dynamic [11C]-(R)PK11195 PET scans. Parametric maps of rCBV and [11C]-(R)PK11195 binding potential (BP) were generated. Co-registered MR/ PET images were used to guide biopsy/resection. The cohort consisted of 12 astrocytomas (5 grade III) and 14 oligodendroglioma (3 grade III) All but one were IDH1R132H mutant; all oligodendrogliomas showed 1p19q co-deletion; low-grade and anaplastic astrocytomas lost ATRX expression. RESULTS: BP and rCBV differed between grade II and III tumours. Both AA and AO demonstrated higher mean and maximal BP of [11C]-(R)PK11195 (mean BP: 0.08 ± 0.18 vs.-0.07 ± 0.15, p=0.032; maximal BP: 1.59 ± 0.63 vs. 0.79 ± 0.28, p=0.001). Increased rCBV was found in oligodendrogliomas grade II and III compared to astrocytomas of similar grade (mean rCBV: 1.38 vs 0.97 and 1.44 vs. 1.09 respectively, p=0.01). Although, no significant increase of rCBV was found in AO and AA compared to lower grade oligodendrogliomas and astrocytomas (mean rCBV of whole tumour: 1.44 vs 1.38 and 1.09 vs.0.97 respectively, p=0.53). To further investigate correlations between rCBV and [11C]-(R)PK11195 BP, we defined a 10mm volume of interest (VOI) on highest uptake of radiotracer and compared with the mean rCBV of the same VOI. A significant correlation was found between BPmax and rCBV of the same 10mm VOI (pairwise correlation coefficient = 0.5984, p= 0.0042). High variance of [11C]-(R)PK11195 binding between grade III gliomas was observed; 5 out of 8 grade III gliomas (3 oligodedrogliomas) demonstrated high BP areas corresponding to or extending beyond areas of enhancement where present. Three grade III tumours with no contrast enhancement showed high [11C]-(R)PK11195 binding. CONCLUSIONS: [11C]-(R)PK11195 has the potential to detect transformation and provides information complimentary to perfusion metrics in early detection of progression.