[18F]Fluoroacetate and [11C]Acetate Small-Animal PET Studies in Rats and Tumor Xenografts in Mice


[18F]Fluoroacetate and [11C]Acetate Small-Animal PET Studies in Rats and Tumor Xenografts in Mice

Bergmann, R.; Richter, S.; Wüst, F.; Beuthien-Baumann, B.; Pietzsch, J.

[18F]Fluoroacetate ([18F]FAC) is discussed as an addition to the well-established PET radiotracer [11C]acetate ([11C]ACE) for the diagnosis and treatment monitoring of low [18F]FDG accumulating cancer entities. The purpose of this study was to establish a reproducible method of [18F]FAC synthesis, and to assess the biodistribution and kinetics in rats and tumor bearing mice to evaluate the potential of [18F]FAC for tumor imaging, and to gain information about the [18F]FAC accumulation mechanism in human squamous cell carcinoma (FaDu) and adenocarcinoma (HT-29) xenografts.

Results and Discussion:

The optimized radiosynthesis of n.c.a. sodium [18F]FAC was performed in two steps: (1) Incorporation of fluorine into (methanesulfonyloxy)-acetic acid tert.-butyl ester as the superior labeling precursor in acetonitrile followed by (2) acidic hydrolysis of the resulting [18F]fluoroacetic acid tert.-butyl ester to afford [18F]FAC. Several consecutive purification gave sodium [18F]FAC in very reproducible radiochemical yields in high radiochemical purity (>95%) within 50 min. Arterial blood samples were analyzed and no metabolites of [18F]FAC were observed up to 60 min p.i. [18F]FAC was readily accumulated in FaDu and HT-29 tumors (tumor/muscle 1.8+/-0.2 mean+/-SEM, n=6) as shown in small-animal PET studies. [18F]FAC and [11C]ACE could clearly delineate the tumors and reached a tumor to muscle ratio up to two. Both agents showed a similar biodistribution. The differences were limited to the higher activity accumulation of the [11C]ACE in pancreas, spleen, kidneys, and the slower blood clearance of [18F]FAC. In some animals dehalogenation was observed.

Conclusion:

The remotely-controlled two step/one pot synthesis of [18F]FAC represents a robust and reproducible procedure. The differences of biodistribution between [18F]FAC and [11C]ACE in rats and tumor bearing mice are relatively small. The absence of metabolites in the arterial blood plasma allows using the plasma activity for quantitative kinetic studies without further metabolite analyses.
(Partly supported by the EU project BioCare No. 505785)

Keywords: small-animal PET; 18F-labeling; [18F]fluoroacetate; [11C]acetate; tumor bearing mice

  • Poster
    Joint Molecular Imaging Conference 2007, 08.-11.09.2007, Providence, Rhode Island, USA

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Publ.-Id: 10090