Uptake of 18F-Fluorocholine, 18F-Fluoroethyl-l-Tyrosine, and 18F-FDG in Acute Cerebral Radiation Injury in the Rat: Implications for Separation of Radiation Necrosis from Tumor Recurrence

摘要

Differentiation between posttherapy radiation necrosis and recurrent tumor in humans with brain tumor is still a difficult diagnostic task. The new PET tracers 18F-fluoro-ethyl-l-tyrosine (FET) and 18F-fluorocholine (N,N-dimethyl-N-18F-fluoromethyl-2-hydroxyethylammonium [FCH]) have shown promise for improving diagnostic accuracy. This study assessed uptake of these tracers in experimental radiation injury. Methods: In a first model, circumscribed lesions were induced in the cortex of 35 rats using proton irradiation of 150 or 250 Gy. After radiation injury developed, uptake of 18F-FET, 18F-FCH, and 18F-FDG was measured using autoradiography and correlated with histology and disruption of the blood-brain barrier as determined with Evans blue. In a second model, uptake of the tracers was assessed in acute cryolesions, which are characterized by the absence of inflammatory cells. Results: Mean 18F-FET, 18F-FCH, and 18F-FDG standardized uptake values in the most active part of the radiation lesion and the contralateral normal cortex (in parentheses) were 2.27 ?± 0.46 (1.42 ?± 0.23), 2.52 ?± 0.42 (0.61 ?± 0.12), and 6.21 ?± 1.19 (4.35 ?± 0.47). The degree of uptake of 18F-FCH and 18F-FDG correlated with the density of macrophages. In cryolesions, 18F-FET uptake was similar to that in radiation lesions, and 18F-FCH uptake was significantly reduced. Conclusion: Comparison of tracer accumulation in cryolesions and radiation injuries demonstrates that 18F-FET uptake is most likely due to a disruption of the blood-brain barrier alone, whereas 18F-FCH is additionally trapped by macrophages. Uptake of both tracers in the radiation injuries is generally lower than the published uptake in tumors, suggesting that 18F-FET and 18F-FCH are promising tracers for separating radiation necrosis from tumor recurrence. However, the comparability of our data with the literature is limited by factors such as different species and acquisition protocols and modalities. Thus, more studies are needed to settle this issue. Nevertheless, 18F-FCH and 18F-FET seem superior to 18F-FDG for this purpose.