[18F]FE@SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo study in rodents

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• 作者：Daniela Haeusler ; Claudia Kuntner…
• 关键词：Adenosine A3 receptor ; Small ; animal PET ; [18F]FE@SUPPY ; Xenograft ; Efflux transporter ; Tumour marker
• 刊名：European Journal of Nuclear Medicine and Molecular Imaging
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：42
• 期：5
• 页码：741-749
• 全文大小：697 KB
• 参考文献：1. Gessi, S, Merighi, S, Sacchetto, V, Simioni, C, Borea, PA (1808) Adenosine receptors and cancer. Biochim Biophys Acta 2011: pp. 1400-1412
  2. Wadsak, W, Mien, LK, Shanab, K, Weber, K, Schmidt, B, Sindelar, KM (2008) Radiosynthesis of the adenosine A3 receptor ligand 5-(2-[18F]fluoroethyl)2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate ([18F]FE@SUPPY). Radiochim Acta 96: pp. 119-124 CrossRef
  3. Wadsak, W, Mien, LK, Shanab, K, Ettlinger, DE, Haeusler, D, Sindelar, KM (2008) Preparation and first evaluation of [18F]FE@SUPPY: a new PET tracer for the adenosine A3 receptor. Nucl Med Biol 35: pp. 61-66 CrossRef
  4. Kiesewetter, DO, Lang, L, Ma, Y, Bhattacharjee, AK, Gao, ZG, Joshi, BV (2009) Synthesis and characterization of [76Br]-labeled high-affinity A3 adenosine receptor ligands for positron emission tomography. Nucl Med Biol 36: pp. 3-10 CrossRef
  5. Haeusler, D, Mitterhauser, M, Mien, LK, Shanab, K, Lanzenberger, RR, Schirmer, E (2009) Radiosynthesis of a novel potential adenosine A3 receptor ligand 5-ethyl 2,4-diethyl-3-((2-[18F]fluoroethyl)sulfanylcarbonyl)-6-phenylpyridine-5-carboxylate ([18F]FE@SUPPY:2). Radiochim Acta 97: pp. 753-758 CrossRef
  6. Mitterhauser, M, Haeusler, D, Mien, LK, Ungersboeck, J, Nics, L, Lanzenberger, RR (2009) Automatisation and first evaluation of [18F]FE@SUPPY:2, an alternative PET-tracer for the adenosine A3 receptor: a comparison with [18F]FE@SUPPY. Open Nucl Med J 1: pp. 15-23 CrossRef
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  10. Balber, T, Haeusler, D, Wadsak, W, Hacker, M, Shanab, K, Spreitzer, H (2013) Is there a better ligand for the A3R than FE@SUPPY as a potential PET-tracer?. Nuklearmedizin 6: pp. A138
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  12. Haeusler, D, Nics, L, Mien, LK, Ungersboeck, J, Lanzenberger, R, Shanab, K (2010) [18F]FE@SUPPY and [18F]FE@SUPPY:2 -metabolic considerations. Nucl Med Biol 37: pp. 421-426 CrossRef
  13. Haeusler, D, Szerencsics, E, Girschele, F, Dudczak, R, Wadsak, W, Mitterhauser, M (2011) An autoradiographic study regarding the adenosine A3 receptor on human and rat brain tissues [abstract]. Eur J Nucl Med Mol Imaging 38: pp. 149S
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  17. Fueger BJ, Czernin
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Nuclear Medicine
  Imaging and Radiology
  Orthopedics
  Cardiology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1619-7089

文摘

Purpose The adenosine A3 receptor (A3R) is involved in cardiovascular, neurological and tumour-related pathologies and serves as an exceptional pharmaceutical target in the clinical setting. A3R antagonists are considered antiinflammatory, antiallergic and anticancer agents, and to have potential for the treatment of asthma, COPD, glaucoma and stroke. Hence, an appropriate A3R PET tracer would be highly beneficial for the diagnosis and therapy monitoring of these diseases. Therefore, in this preclinical in vivo study we evaluated the potential as a PET tracer of the A3R antagonist [18F]FE@SUPPY. Methods Rats were injected with [18F]FE@SUPPY for baseline scans and blocking scans (A3R with MRS1523 or FE@SUPPY, P-gp with tariquidar; three animals each). Additionally, metabolism was studied in plasma and brain. In a preliminary experiment in a mouse xenograft model (mice injected with cells expressing the human A3R; three animals), the animals received [18F]FE@SUPPY and [18F]FDG. Dynamic PET imaging was performed (60?min in rats, 90?min in xenografted mice). In vitro stability of [18F]FE@SUPPY in human and rat plasma was also evaluated. Results [18F]FE@SUPPY showed high uptake in fat-rich regions and low uptake in the brain. Pretreatment with MRS1523 led to a decrease in [18F]FE@SUPPY uptake (p--.03), and pretreatment with the P-gp inhibitor tariquidar led to a 1.24-fold increase in [18F]FE@SUPPY uptake (p--.09) in rat brain. There was no significant difference in metabolites in plasma and brain in the treatment groups. However, plasma concentrations of [18F]FE@SUPPY were reduced to levels similar to those in rat brain after blocking. In contrast to [18F]FDG uptake (p--.12), the xenograft model showed significantly increased uptake of [18F]FE@SUPPY in the tissue masses from CHO cells expressing the human A3R (p--.03). [18F]FE@SUPPY was stable in human plasma. Conclusion Selective and significant tracer uptake of [18F]FE@SUPPY was found in xenografted mice injected with cells expressing human A3R. This finding supports the strategy of evaluating [18F]FE@SUPPY in “humanized animal models- In conclusion, preclinical evaluation points to the suitability of [18F]FE@SUPPY as an A3R PET tracer in humans.