TO THE EDITOR: We read with great interest the recent article by Filss et al. published in The Journal of Nuclear Medicine (1). They observed a considerable increase of 18F-FET uptake in 26% of subjects compared with preoperative values adjacent to the resection cavity with subsequent decrease in follow-up PET in most of the patients. The authors did not directly study the histopathology, but hypothesized that surgical intervention stimulated the metabolic activity of infiltrating tumor tissue with low metabolic activity before surgery. This is a very important study given the growing interest in using amino acid PET for target volume definition for radiotherapy beyond MRI signal abnormality (2,3), and clinicians should be aware of this phenomenon especially during the first 2 wk after surgery.
Postoperative ischemic changes after glioma resection are very common and can be diagnosed on early postoperative MRI by diffusion-weighted imaging. In a study of 104 patients with newly diagnosed and recurrent glioma (4), these postoperative ischemic lesions were identified in 31% of patients with newly diagnosed gliomas and 80% patients with recurrent gliomas (4). It is important to mention that most of these ischemic lesions were clinically silent, and only 24% of patients with newly diagnosed glioma and 48% of patients with recurrent glioma had new neurologic deficits (4). In another study of 251 glioblastoma patients who underwent surgery, postoperative infarct volume significantly correlated as an independent variable with overall survival (5), and the authors suggested that hypoxia might mediate invasive tumor growth and contribute to decreased survival (5).
A multitracer PET study to investigate amino acid accumulation in brain tissue surrounding focal ischemia demonstrated 11C-MET uptake not only in the core of ischemia but also in surviving brain tissue surrounding infarction likely representing alterations of amino acid transport or protein synthesis (6). Increased 18F-FET uptake in subacute ischemia is also anecdotally reported by others (7,8). In a preclinical study of focal cortical ischemia induction in rats, increased uptake of 18F-FET was observed in the ischemic lesions for up to 7 days and the lesion-to-brain (L/B) ratio cutoff of 2 was exceeded in 48% of animals (9).
We believe that the high incidence of postoperative ischemic and other nonspecific changes that result in increased 18F-FET uptake even in the absence of viable tumor may diminish the specificity of 18F-FET PET early in the postoperative period. Filss et al. could test this hypothesis by correlating the location of postoperative ischemia on diffusion-weighted images with increased 18F-FET uptake. If concordance is seen, early postoperative MRI might provide important information with regard to the spatial location of ischemia compared with increased 18F-FET uptake and may warrant a delay in postoperative PET until nonspecific postoperative causes of uptake have resolved.
Footnotes
Published online Jul. 9, 2020.
- © 2020 by the Society of Nuclear Medicine and Molecular Imaging.