Correlation of F-18-fluoro-ethyl-tyrosin uptake with vascular and cell density in non-contrast-enhancing gliomas

Objective Even without contrast enhancement on MRI scans gliomas can show histological features of anaplasia. These tumors are heterogeneous regarding anaplastic and non-anaplastic areas. Increased amino acid uptake was shown to be associated with dismal prognosis in gliomas. We investigated histological correlates of tumor grading in biopsies obtained from regions with maximum amino acid uptake revealed by F-18-fluoro-ethyl-tyrosin positron emission tomography (FET-PET). Methods We included 22 patients with non-contrast enhancing lesions on MRI scans. PET was performed 10 min after FET injection, and the area of maximum FET uptake was chosen as the biopsy target. In 13 patients neuronavigated biopsies were obtained during tumor resection. Nine patients had a stereotactic biopsy. The ratio of maximum standardized uptake value (SUV) to background was calculated. Histological specimens were classified and graded according to world health organization (WHO) criteria. We investigated cell and vascular density, mitotic activity, proliferation index, microvascular proliferation, nuclear pleomorphism, necrosis and immunoreactivity of LAT1 (SLC7A5), an amino acid transporter with prognostic impact in gliomas. Results 12 of the 22 non-contrast enhancing gliomas corresponded to anaplastic astrocytomas WHO grade III. Vascular and cellular density was correlated highly to the SUV ratio (P = 0.0015 and P = 0.0021, respectively), but with no nuclear pleomorphism, mitotic activity, Mib-1 immunoreactivity, or microvascular proliferation. Thus, no correlation was found between FET uptake and tumor grade. Conclusion FET-PET correlates with vascular and cell density in non-contrast enhancing gliomas. Although tumor grade cannot be predicted, clinical use of FET PET as an indicator for neovascularization should be addressed in future studies. Florian Stockhammer and Michail Plotkin contributed equally to this work. Christian Woiciechowsky and Frank van Landeghem contributed equally to this work.