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 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 si...

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Published in:Nuclear medicine and biology 2013-08, Vol.40 (6), p.808-815
Main Authors: Sasajima, Toshio, Ono, Takahiro, Shimada, Naoya, Doi, Yoshihiro, Oka, Shuntaro, Kanagawa, Masaru, Baden, Atsumi, Mizoi, Kazuo
Format: Article
Language:English
Subjects:
Animals
Anti-FACBC
Blood-Brain Barrier - metabolism
Brain Neoplasms - diagnosis
Brain Neoplasms - drug therapy
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Carboxylic Acids - metabolism
Cell Line, Tumor
Cell Proliferation - drug effects
Cyclobutanes - metabolism
Dacarbazine - analogs & derivatives
Dacarbazine - pharmacology
Dacarbazine - therapeutic use
Feasibility Studies
Glioma
Glioma - diagnosis
Glioma - drug therapy
Glioma - metabolism
Glioma - pathology
Magnetic Resonance Imaging - methods
Male
Methionine - analogs & derivatives
Methionine - metabolism
Methyl-l-methionine
MRI
Permeability
Rats
Temozolomide
Treatment Outcome
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Summary:Amino 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. C6 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. The 3H-TdR accumulation rate and amino acid tracer (anti-14C-FACBC and 3H-Met) uptake significantly decreased 48 and 72h, 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. Anti-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.
ISSN:0969-8051
1872-9614
DOI:10.1016/j.nucmedbio.2013.04.007