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PET of Glial Metabolism Using 2-¹⁸F-Fluoroacetate

¹ Biomedical Imaging, Genentech Inc., South San Francisco, California; ² Department of Tumor Biology and Angiogenesis, Genentech Inc., South San Francisco, California; ³ Research Pathology, Genentech Inc., South San Francisco, California; and ⁴ Early Development PKPD, Genentech Inc., South San Francisco, California

View larger version (41K): [in this window] [in a new window]   FIGURE 1.  Orthotopic glioblastoma xenograft in mice. Time–activity curves for 18F-FAC (A) and 18F-FDG (B). Correlation of tumor volumes determined by MRI with 18F-FAC (R2 = 0.934, P = 0.007) (C) and 18F-FDG (R2 = 0.416, P = 0.240) (D). Representative coronal section of whole head (animal 5), with brain tumor detected in vivo by 18F-FAC (E), 18F-FDG (F), MRI (G), and corresponding brain section stained with H&E (H).

View larger version (49K): [in this window] [in a new window]   FIGURE 2.  Cerebral focal ischemia model in rat. Time–activity curves for 18F-FAC (A) and 18F-FDG (B). Correlation of infarct volume determined by TTC with volumes determined by 18F-FAC (R2 = 0.692, P = 0.010) (C) and by 18F-FDG (R2 = 0.295, P = 0.208) (D). Representative coronal section of whole rat head with ischemic brain injury (dotted line) detected in vivo by 18F-FAC (animal 79) (E), 18F-FDG (animal 66) (F), and corresponding brain section from animal 79 stained by TTC (G) and anti-GFAP (H).

View larger version (22K): [in this window] [in a new window]   FIGURE 3.  Time–activity profiles (A) obtained during dual-tracer PET experiment using rat focal ischemia model (n = 3). 18F-FDG was injected at 0 min, followed by 18F-FAC at 30 min. Representative coronal sections of rat brains with MCAO-induced injury: 18F-FDG image obtained in first 30 min (B), and 18F-FAC image (C) obtained after subtraction. For multispectral analysis (D), areas are color-coded as follows: green (18F-FDG low, 18F-FAC low), red (18F-FDG high, 18F-FAC low), yellow (18F-FDG low, 18F-FAC high), and blue (18F-FAC high, 18F-FDG high).

View larger version (43K): [in this window] [in a new window]   FIGURE 4.  Cerebral ischemia–hypoxia mouse model. Time–activity curves for 18F-FAC (A) and 18F-FDG (B). Representative coronal section of whole mouse head with ischemia–hypoxia–induced brain injury detected in vivo by 18F-FAC (animal F2) (C), 18F-FDG (animal P2) (D), and corresponding brain section stained with TTC (animal F2) (E).

View larger version (70K): [in this window] [in a new window]   FIGURE 5.  Coronal section of whole mouse head with brain affected by ischemia–hypoxia: 18F-FAC uptake at 30 and 90 min and ex vivo TTC staining at 120 min after common carotid occlusion and hypoxia (animals M2 and M5).