| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2153676 | Nuclear Medicine and Biology | 2013 | 8 Pages |
IntroductionAmino acid PET tracers are promising for visualizing gliomas and evaluating radiochemotherapeutic effects. We compared the glioma detection and early response assessment utility between trans-1-amino-3-fluoro-1-14C-cyclobutanecarboxylic acid (anti-14C-FACBC) and 3H-methyl-l-methionine (3H-Met) by simultaneously analyzing their uptake by rat gliomas treated with and without temozolomide (TMZ) in vitro and in vivo.MethodsC6 rat gliomas were incubated with low-dose TMZ to induce chemoresistance. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated a significantly greater surviving fraction in the TMZ-resistant subline (C6R) than in drug-naive cells (C6). The anti-14C-FACBC and 3H-Met uptakes were quantified using a triple-label accumulation assay to examine the relationship between tracer uptake and proliferation (3H-thymidine (TdR) accumulation rate) in tumor cells. C6 and C6R cells were inoculated into the right and left basal ganglia, respectively, of rats. Efficacy of TMZ against the orthotopic gliomas was analyzed by MRI, Evans blue extravasation, anti-14C-FACBC and 3H-Met autoradiography, and MIB-5 proliferation index.ResultsThe 3H-TdR accumulation rate and amino acid tracer (anti-14C-FACBC and 3H-Met) uptake significantly decreased 48 and 72 h, respectively, after TMZ treatment in C6 but not C6R cells. Anti-14C-FACBC uptake correlated significantly with 3H-Met uptake and the 3H-TdR accumulation rate. In the intracerebral glioma model, anti-14C-FACBC and 3H-Met autoradiography clearly delineated the tumor extent, which spread well beyond the high-T2-intensity and enhancing lesions visible on MRI and Evans blue extravasation. TMZ significantly decreased anti-14C-FACBC and 3H-Met uptake and the MIB-5 index of C6 but not C6R tumors. TMZ inhibited tracer uptake and tumor proliferation before morphological changes on MRI.ConclusionsAnti-14C-FACBC, like 3H-Met, was more sensitive than post-contrast T1-weighted MRI for detecting tumor extent and early tumor response to TMZ treatment. Anti-18F-FACBC should be a sensitive and precise imaging biomarker for tumor extent visualization and response assessment in glioma patients.
