Synthesis and biological evaluation of F-18-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging

In the search for an efficient, fluorine-18 labeled amino acid based radiotracer for tumor imaging with positron emission tomography (PET), two new tryptophan analogs were synthesized and characterized in vitro and in vivo. Both are tryptophan alkyl-derivatives, namely 2-(3-[F-18]fluoropropyl)-DL-tr...

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Published inEuropean journal of medicinal chemistry Vol. 70; pp. 768 - 780
Main Authors Chiotellis, Aristeidis, Mu, Linjing, Mueller, Adrienne, Selivanova, Svetlana V., Keller, Claudia, Schibli, Roger, Kraemer, Stefanie D., Ametamey, Simon M.
Format Journal Article
LanguageEnglish
Published PARIS Elsevier 01.12.2013
Subjects
Chemistry, Medicinal
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Science & Technology
AMINO-ACID DECARBOXYLASE
Tryptophan
Amino acids
CELL-LINES
UPTAKE MECHANISMS
IMPROVED SELECTIVITY
TRANSPORT
POSITRON-EMISSION-TOMOGRAPHY
CLINICAL-APPLICATIONS
PROSTATE-CANCER
Tumor imaging
D-ISOMERS
EXPRESSION
PET
LAT
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Summary:In the search for an efficient, fluorine-18 labeled amino acid based radiotracer for tumor imaging with positron emission tomography (PET), two new tryptophan analogs were synthesized and characterized in vitro and in vivo. Both are tryptophan alkyl-derivatives, namely 2-(3-[F-18]fluoropropyl)-DL-tryptophan ([F-18]2-FPTRP) and 5-(3-[F-18]fluoro-propyl)-DL-tryptophan ([F-18]5-FPTRP) Standard reference compounds and precursors were prepared by multi step approaches. Radiosynthesis was achieved by nocarrier-added nucleophilic [F-18]fluorination in 29-34% decay corrected yields with radiochemical purity over 99%. In vitro cell uptake assays showed that both compounds are substrates for amino acid transport and enter small cell lung cancer cells (NCI-H69) most probably almost exclusively via large neutral amino acids transporter(s) (LAT). Small animal PET imaging with xenograft bearing mice revealed high tumor/background ratios for [F-18]2-FPTRP comparable to the well established tyrosine analog O-(2-[F-18]fluroethyl)-L-tyrosine ([F-18]FET). Radiometabolite studies showed no evidence of involvement of a biotransformation step in tumor accumulation. (C) 2013 Elsevier Masson SAS. All rights reserved.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2013.10.054