18F-methylcholine PET/CT, in vivo magnetic resonance spectroscopy imaging and tissue enzyme biomarkers of choline metabolism in primary brain gliomas

Pilot C-11/ F-18 choline PET studies show differential uptake between benign and malignant tumours, however the cellular and molecular basis of this uptake and MRS-visible choline containing compounds (Cho) is not well understood. Choline kinase-α phosphorylates choline, an essential step in membrane synthesis, and is expressed by malignant tumours; it presents a potential novel therapeutic target. We investigate the relationship between choline metabolism detected in vivo using MRS and PET, CKα expression and proliferation in anatomically-defined locations within gliomas. Prospective pilot study. 14 patients with suspected primary glioma underwent multimodal 3T MRI (including multi-voxel MRS) and dynamic 18F-FMC PET/CT prior to surgery. Co-registered PET and MRI data were used to identify regions of high and low choline, and targeted biopsies were performed using a surgical planning tool. Immunohistochemistry for CKα expression was performed on these samples. All tumours showed increased tracer uptake relative to contralateral white matter. Significant differences in TBR were found between WHO grade IV and WHO grades I, II & III tumours in 18F-FMC uptake and between WHO grades IV&III and WHO grades I&II using Cho/Cr ratios on MRS. Combining PET and MRS data showed spatial concordance between regions of high PET uptake and highest Cho/Cr ratio, however there was no correlation between the actual levels of uptake (TBR) and the Cho/Cr ratio in these regions. Furthermore, regions of contrast enhancement on MRI showed high uptake on PET. CKα expression assays showed no simple relationship with imaging parameters. Combining 18F-FMC uptake and Cho/Cr ratio on MRS may help stratify aggressive glioma phenotypes. Establishing the relationship between imaging-derived choline biomarkers markers and CKα expression is challenging, and may be confounded by both physiological and technical factors.