PET of Glial Metabolism Using 2-¹⁸F-Fluoroacetate

Abstract

Imaging of the glial activation that occurs in response to central nervous system trauma and inflammation could become a powerful technique for the assessment of several neuropathologies. The selective uptake and metabolism of 2-18 F-fluoroacetate ( 18 F-FAC) in glia may represent an attractive strategy for imaging glial metabolism. Methods: We have evaluated the use of 18 F-FAC as a specific PET tracer of glial cell metabolism in rodent models of glioblastoma, stroke, and ischemia-hypoxia. Results: Enhanced uptake of 18 F-FAC was observed (6.98 6 0.43 percentage injected dose per gram [%ID/g]; tumor-to-normal ratio, 1.40) in orthotopic U87 xenografts, compared with healthy brain tissue. The lesion extent determined by 18 F-FAC PET correlated with that determined by MRI (R 2 5 0.934, P 5 0.007). After transient middle cerebral artery occlusion in the rat brain, elevated uptake of 18 F-FAC (1.00 6 0.03 %ID/g; lesion-to-normal ratio, 1.90) depicted the ischemic territory and correlated with infarct volumes as determined by 2,3,5-triphenyltetrazolium chloride staining (R 2 5 0.692, P 5 0.010) and with the presence of activated astrocytes detected by anti-glial fibrillary acidic protein.Ischemia-hypoxia, induced by permanent ligation of the common carotid artery with transient hypoxia, resulted in persistent elevation of 18 F-FAC uptake within 30 min of the induction of hypoxia. Conclusion: Our data support the further evaluation of 18 F-FAC PET for the assessment of glial cell metabolism associated with neuroinflammation.

Evaluation of 2-[18F]fluoroacetate Kinetics in Rodent Models of Cerebral Hypoxia–Ischemia

“…17 Our data also showed some bone uptake in rat data toward the latter part of acquisition. In addition, hyperintense regions in k 3 maps were observed to coincide with skeletal structures, suggesting [ 18 17,19 Furthermore, defluorination is not as prevalent in non-human primates, with bone uptake at 3% of injected dose in cynomolgus monkeys but 39% in pigs. 18 In baboons, the specific uptake value of iliac bone was reported to be low even 2 hours post [ 18 F]FACE injection.…”

“…Parametric images of apparent diffusion coefficient (ADC) were then calculated from this data. For both mouse and rat, T2 parametric images were calculated from data acquired with a multispin echo sequence with the following parameters: repetition time, 3,000 milliseconds; echo time, 19 and delivered via tail vein infusion at an average activity concentration of 249 ± 96 mCi (mouse) or 853±104 mCi (rat) in 100 mL saline during the first minute of a 30-minute (mouse) or 90-minute (rat) dynamic scan. A short infusion delivery was selected for reproducibility and peak identifiability given the chosen frame durations.…”

“…14 In the past, this mechanism has been exploited by the use of sodium fluoroacetate as a potent rodenticide and also for the study of brain metabolism. 15,16 The use of [ 18 19,20 These results suggested the intriguing possibility that the observed [ 18 F]FACE uptake is metabolism-driven, thus suggesting the potential use of this tracer for imaging glia-specific metabolism in these animal models. In this study, we have investigated the extent to which [ 18 F]FACE uptake in cerebral H-I is driven by metabolism or by other factors.…”

2-18F-Fluoroacetate: A Useful Tool for Assessing Gliosis in the Central Nervous System?

“…The work of Marik et al (25), presented in this issue of The Journal of Nuclear Medicine, is the first study, to our knowledge, to examine the utility of 18 F-FAC as a noninvasive index of glial cell metabolism. The study provides an intriguing first look at what might represent a novel and potentially useful application for imaging CNS inflammation.…”

Increase in [18F]-Fluoroacetate Uptake in Patients With Chronic Hemodynamic Cerebral Ischemia

“…Experimental studies using positron emission tomography (PET) have shown an increase in the uptake of 18 F-FACE in rodent models of cerebral ischemia, although the precise mechanism for the increased uptake of 18 F-FACE was not determined. 4 Because the increased 18 F-FACE uptake was correlated with infarct volumes, these studies have suggested that the increased 18 F-FACE uptake may reflect the brain regions that are most at risk for ischemic damage. However, there has been no evaluation of 18 F-FACE PET in patients with ischemic stroke.…”