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Imaging tumour ATB0,+ transport activity by PET with the cationic amino acid O-2((2-[18F]fluoroethyl)methyl-amino)ethyltyrosine


Müller, Adrienne; Chiotellis, Aristeidis; Keller, Claudia; Ametamey, Simon M; Schibli, Roger; Mu, Linjing; Krämer, Stefanie D (2014). Imaging tumour ATB0,+ transport activity by PET with the cationic amino acid O-2((2-[18F]fluoroethyl)methyl-amino)ethyltyrosine. Molecular Imaging and Biology, 16(3):412-420.

Abstract

PURPOSE The concentrative amino acid transporter ATB(0,+) (SLC6A14) is under evaluation as a target for anticancer therapy. An ATB(0,+)-selective positron emission tomography (PET) probe could advance preclinical drug development. We characterised the cationic tyrosine analogue O-2((2-[(18)F]fluoroethyl)methyl-amino)ethyltyrosine ([(18)F]FEMAET) as a PET probe for ATB(0,+) activity. PROCEDURES Cell uptake was studied in vitro. ATB(0,+) expression was quantified by real-time PCR. [(18)F]FEMAET accumulation in xenografts was investigated by small animal PET with mice. RESULTS [(18)F]FEMAET accumulated in PC-3 and NCI-H69 cancer cells in vitro. As expected for ATB(0,+) transport, uptake was inhibited by LAT/ATB(0,+) inhibitors and dibasic amino acids, and [(18)F]FEMAET efflux was only moderately stimulated by extracellular amino acids. ATB(0,+) was expressed in PC-3 and NCI-H69 but not MDA-MB-231 xenografts. PET revealed accumulation in PC-3 and NCI-H69 xenografts and significant reduction by ATB(0,+) inhibition. Uptake was negligible in MDA-MB-231 xenografts. CONCLUSION ATB(0,+) activity can be imaged in vivo by PET with [(18)F]FEMAET.

Abstract

PURPOSE The concentrative amino acid transporter ATB(0,+) (SLC6A14) is under evaluation as a target for anticancer therapy. An ATB(0,+)-selective positron emission tomography (PET) probe could advance preclinical drug development. We characterised the cationic tyrosine analogue O-2((2-[(18)F]fluoroethyl)methyl-amino)ethyltyrosine ([(18)F]FEMAET) as a PET probe for ATB(0,+) activity. PROCEDURES Cell uptake was studied in vitro. ATB(0,+) expression was quantified by real-time PCR. [(18)F]FEMAET accumulation in xenografts was investigated by small animal PET with mice. RESULTS [(18)F]FEMAET accumulated in PC-3 and NCI-H69 cancer cells in vitro. As expected for ATB(0,+) transport, uptake was inhibited by LAT/ATB(0,+) inhibitors and dibasic amino acids, and [(18)F]FEMAET efflux was only moderately stimulated by extracellular amino acids. ATB(0,+) was expressed in PC-3 and NCI-H69 but not MDA-MB-231 xenografts. PET revealed accumulation in PC-3 and NCI-H69 xenografts and significant reduction by ATB(0,+) inhibition. Uptake was negligible in MDA-MB-231 xenografts. CONCLUSION ATB(0,+) activity can be imaged in vivo by PET with [(18)F]FEMAET.

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11 citations in Web of Science®
11 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nuclear Medicine
Dewey Decimal Classification:610 Medicine & health
Date:June 2014
Deposited On:12 Feb 2015 13:43
Last Modified:05 Apr 2016 19:06
Publisher:Springer
ISSN:1536-1632
Publisher DOI:https://doi.org/10.1007/s11307-013-0711-2
PubMed ID:24307544

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