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Differences in Transport Mechanisms of trans-1-Amino-3-[18F]Fluorocyclobutanecarboxylic Acid in Inflammation, Prostate Cancer, and Glioma Cells: Comparison with l-[Methyl-11C]Methionine and 2-Deoxy-2-[18F]Fluoro-d-Glucose

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Abstract

Purpose

We aimed to elucidate trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid (anti-[18F]FACBC) uptake mechanisms in inflammatory and tumor cells, in comparison with those of l-[methyl-11C]methionine ([11C]Met) and 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG).

Procedures

Using carbon-14-labeled tracers, in vitro time-course, pH dependence, and competitive inhibition uptake experiments were performed in rat inflammatory (T cells, B cells, granulocytes, macrophages), prostate cancer (MLLB2), and glioma (C6) cells.

Results

Anti-[14C]FACBC uptake ratios of T/B cells to tumor cells were comparable, while those of granulocytes/macrophages to tumor cells were lower than those for [14C]FDG. Over half of anti-[14C]FACBC uptake by T/B and tumor cells was mediated by Na+-dependent amino acid transporters (system ASC), whereas most [14C]Met transport in all cells was mediated by Na+-independent carriers (system L).

Conclusions

The low anti-[18F]FACBC accumulation in granulocytes/macrophages may be advantageous in discriminating inflamed regions from tumors. The significant anti-[18F]FACBC uptake in T/B cells may cause false-positives in some cancer patients who undergo FACBC-positron emission tomography (PET).

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Acknowledgments

The authors thank Mr. Shiro Yoshida and Ms. Sachiko Naito for their assistance in animal treatments and cell cultures, respectively.

Conflict of interest

Shuntaro Oka, Hiroyuki Okudaira, Masahiro Ono, and Yoshifumi Shirakami are employees of Nihon Medi-Physics Co. Ltd. Mark M. Goodman and Emory University have patent rights for anti-[18F]FACBC and are eligible to receive royalties on anti-[18F]FACBC from Nihon Medi-Physics Co. Ltd. Mark M. Goodman, David M. Schuster, and Keiichi Kawai have ongoing research collaborations with Nihon Medi-Physics Co. Ltd.

Author information

Authors and Affiliations

  1. Research Center, Nihon Medi-Physics Co., Ltd, Chiba, Japan

    Shuntaro Oka, Hiroyuki Okudaira, Masahiro Ono & Yoshifumi Shirakami

  2. Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan

    Masahiro Ono & Keiichi Kawai

  3. Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, USA

    David M. Schuster & Mark M. Goodman

  4. Biomedical Imaging Research Center, University of Fukui, Fukui, Japan

    Keiichi Kawai

  5. Kitasode 3-1, Sodegaura, Chiba, 299-0266, Japan

    Shuntaro Oka

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  1. Shuntaro Oka
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Correspondence to Shuntaro Oka.

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Oka, S., Okudaira, H., Ono, M. et al. Differences in Transport Mechanisms of trans-1-Amino-3-[18F]Fluorocyclobutanecarboxylic Acid in Inflammation, Prostate Cancer, and Glioma Cells: Comparison with l-[Methyl-11C]Methionine and 2-Deoxy-2-[18F]Fluoro-d-Glucose. Mol Imaging Biol 16, 322–329 (2014). https://doi.org/10.1007/s11307-013-0693-0

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