Treatment-Related Uptake of O-(2-18F-Fluoroethyl)-l-Tyrosine and l-[Methyl-3H]-Methionine After Tumor Resection in Rat Glioma Models

Abstract

Assessment of residual tumor after resection of cerebral gliomas can be difficult with MRI and may be improved by amino acid PET. The aim of this experimental study was to investigate uptake of 2-¹⁸F-fluoroethyl-l-tyrosine (¹⁸F-FET) and l-[methyl-³H]-methionine (³H-MET) in residual tumor after surgery and possible false-positive uptake in treatment-related changes. Methods: F98 or GS-9L rat gliomas were implanted into the brain of 64 rats. Tumors were resected after 1 wk of tumor growth, and sham surgery was performed in an additional 10 animals. At different time points after surgery (1, 2, 3, 7, and 14-16 d), rats underwent ex vivo dual-tracer autoradiography using ¹⁸F-FET and ³H-MET. Histologic slices were evaluated by immunostaining for cell density and astrogliosis. Tracer uptake was quantified by lesion-to-brain ratios (L/B) at the rim of the resection cavity (considered treatment-related uptake) and in residual or recurrent tumor tissue. Four animals showing no residual tumor underwent PET 3 d after surgery to examine time-activity curves of ¹⁸F-FET uptake in treatment-related changes. Results: Treatment-related uptake with a mean L/B of 2.0 ± 0.3 for ¹⁸F-FET and a mean L/B of 1.7 ± 0.2 for ³H-MET was noted at the rim of the resection cavity in the first week after surgery, decreasing significantly by 14-16 d (P < 0.01). Treatment-related tracer uptake was significantly higher for ¹⁸F-FET than for ³H-MET (P < 0.001). Tracer uptake in rat gliomas exceeded treatment-related tracer uptake at all time points (P < 0.001), but the latter was in the range of human gliomas. Reactive astrogliosis was noted near the resection cavity from the second day after surgery. Time-activity curves of ¹⁸F-FET uptake in those areas revealed constantly increasing uptake. Conclusion: Surgery may induce significant treatment-related ¹⁸F-FET and ³H-MET uptake near the resection cavity in the first week after surgery, presumably caused by reactive astrogliosis. Treatment-related tracer uptake was less pronounced for ³H-MET, indicating that ¹¹C-MET may be better suited for assessing the postoperative situation than ¹⁸F-FET. Assessment of residual tumor after surgery by amino acid PET seems to be more reliable after an interval of 14 d.

Keywords: 18F-FET; 2-18F-fluoroethyl-l-tyrosine; 3H-MET; PET; glioma; l-[methyl-3H]-methionine; tumor resection.