Abstract
BACKGROUND: Choline containing compounds are key components of cell membranes; their metabolism important in membrane turnover, and therefore cellular proliferation. Choline elevation has been reported as a marker of aggressive glioma phenotype in numerous in vivo magnetic resonance spectroscopy (MRS) studies, and more recently 18F-methylcholine-PET has been applied to glioma characterisation. This preliminary study aims to examine the relationship between MRS and PET imaging choline measures in defined tumour regions, and validate these against tissue biomarkers of choline metabolism and proliferation. METHODS: A prospective pilot study of 12 subjects, aged 18-80, with suspected primary supratentorial glioma of varying grades suitable for biopsy/resection. An MRI protocol, including multivoxel MRS (TE = 30ms; TR = 1500ms), was acquired at 3T using a 32 channel head coil; PET/CT was performed with 285MBq of 18F-methylcholine with a dedicated 45 minute brain dynamic list mode acquisition. Stereotactic biopsies were obtained using neuronavigation from low and high choline areas identified on imaging, fused with high resolution structural images. RESULTS: Preliminary data from 8 patients suggests spatial concordance between high choline uptake on PET and elevated MRS choline/creatine ratios. Tissue from 4 patients (2 WHO grade-II, 2 grade-III) showed high choline areas on imaging correlate with reactive gliosis and macrophage infiltrates, but no mitotic activity or denser cellularity. In one predominantly grade II astrocytoma, areas of elevated uptake on PET showed denser cellularity and mitoses, in keeping with early malignant progression. CONCLUSIONS: Preliminary findings suggest choline PET and MRS may detect regions of inflammatory infiltrate, rather than showing a simple relationship with high tumour cellular proliferation. In one case, elevated choline uptake on PET corresponded to early focal malignant transformation. Whilst these imaging methods show continued promise for glioma characterisation, further validation against tissue enzymatic and genetic biomarkers, and clinical outcomes is essential for their rational translation into wider clinical practice.
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