Methyl-[¹¹C]-l-methionine uptake as measured by positron emission tomography correlates to microvessel density in patients with glioma

Positron emission tomography (PET) using methyl-[¹¹C]-l-methionine ([¹¹C]MET) is a useful tool in the diagnosis of brain tumours. The main mechanism of [¹¹C]MET uptake is probably increased transport via the L-transporter system located in the endothelial cell membrane. We used [¹¹C]MET-PET and microvessel count in glioma specimens to investigate whether the increased amino acid uptake is related to angiogenesis. Twenty-one patients with newly diagnosed and histologically confirmed glioma were investigated with [¹¹C]MET-PET before open surgery. [¹¹C]MET uptake was determined within an 8-mm region of interest in the area of the tumour showing the highest uptake, and the ratio to uptake in the corresponding contralateral region was calculated. To measure angiogenesis, immunostaining with factor VIII antibody was applied to sections from tumour tissue, and highlighted microvessels were counted in the area of highest vascularisation. In the entire patient group, a positive correlation was found between microvessel count and [¹¹C]MET uptake (Spearman: r=0.89, P<0.001). This correlation was also significant in subgroups of patients [patients with grade II and III astrocytomas (Spearman: r=0.77, P<0.01) and patients with glioblastoma (Spearman: r=0.64, P<0.05)]. Angiogenesis, as assessed by microvessel count, and increased amino acid uptake, as assessed by [¹¹C]MET-PET, are closely related events in gliomas. [¹¹C]MET-PET offers a direct measure of amino acid transport and an indirect measure of microvessel density. [¹¹C]MET-PET might be a useful tool to select potential responders to anti-angiogenic therapy and to monitor patients during such therapy.