Trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid (anti-18F-FACBC) is a feasible alternative to 11C-methyl-L-methionine and magnetic resonance imaging for monitoring treatment response in gliomas

Amino acid PET tracers are reliable markers of treatment responses to single-agent or combination therapies including temozolomide, interferon-β, and/or bevacizumab for glioblastoma

“…Unsurprisingly, anti-14 C-FACBC accumulation (V d of anti-14 C-FACBC) closely correlated with 3 H-Met accumulation (V d of 3 H-Met) and tumor proliferation (K i of 3 H-TdR). The close correlation of amino acid tracer accumulation and tumor proliferation is consistent with previous reports [29][30][31] and our previous experimental study [18].…”

“…The autoradiographic biodistribution patterns of anti-14 C-FACBC and 3 H-Met correlated with the histological localization of TMZ-resistant cells (U87R) as well as drug-naive cells (U87), while U87R-derived tumors, which showed focal and equivocal expression of VEGF and less Evans blue extravasation, were noted as equivocal tumors on contrast-enhanced T1-weighted and T2-weighted MR images because of the underestimation of tumor extent owing to BBB disruption. These findings are consistent with those for 11 C-Met in human gliomas [32][33][34] and our previous experimental study [18]. A multimodal image fusion study with spatial correlation of 11 C-Met PET, MRI, and stereotactic histology demonstrated that MRI failed to delineate the exact margins of low-or high-grade gliomas [32].…”

“…In another series of experiments, both cell lines were exposed to TMZ (final concentration, 15-250 μM) in combination with IFN (final concentration, 100 IU/mL) and/or Bev (final concentration, 30 μg/mL). Four days after treatment, MTT cytotoxicity assays were performed as previously described [18]. The cytotoxicity of the single agent or combination was expressed as the percent surviving fraction, calculated as surviving fraction (%) = optical density (treated)/optical density (non-treated) × 100.…”

“…Anesthetic gas supply was maintained throughout imaging via tubing attached hermetically to the holder system. T2-weighted and post-contrast (Gd) T1-weighted images were obtained as previously described [18].…”

“…Brains were immediately removed and frozen in acetone with powdered dry ice prior to sectioning. Double-labeled autoradiography was performed as previously described [18,22,23]. First, standard imaging plates (BAS IP MS, GE Healthcare) were exposed to dried coronal sections (20 μm thick) and [ 14 C] autoradiographic standards (GE Healthcare) for 6 days to generate autoradiograms, which provide quantitative measurements of anti-14 C-FACBC represented by the differential absorption ratio (DAR).…”