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 in | European journal of medicinal chemistry Vol. 70; pp. 768 - 780 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
PARIS
Elsevier
01.12.2013
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Subjects | |
Online Access | Get full text |
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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. |
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ISSN: | 0223-5234 1768-3254 |
DOI: | 10.1016/j.ejmech.2013.10.054 |