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

Chiotellis A; Mu L; Müller A; Selivanova SV; Keller C; Schibli R; Krämer SD; Ametamey SM

doi:10.1016/j.ejmech.2013.10.054

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Journal article

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

Chiotellis A Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Zurich, Switzerland.
Mu L
Müller A
Selivanova SV
Keller C
Schibli R
Krämer SD
Ametamey SM

2013-11-19

Published in:

European journal of medicinal chemistry. - 2013

2-(3-[(18)F]fluoropropyl)-dl-tryptophan)

2-amino-2-norbornanecarboxylic acid

2-deoxy-2-((18)F)fluoro-d-glucose

3-[(123)I]iodo-alpha-methyl-l-tyrosine)

5-(2-[(18)F]fluoroethoxy)-l-tryptophan

5-(3-[(18)F]fluoropropyl)-dl-tryptophan

5-hydroxy-l-[β-(11)C]tryptophan

L-3,4-dihydroxy-6-[(18)F]fluorophenylalanine

O-(2-[(18)F]fluroethyl)-l-tyrosine

amine precursor uptake and decarboxylation

anti-1-amino-3-[(18)F]-fluoro-cyclobutane-1-carboxylic acid

aromatic amino acid decarboxylase

tetrabutylammonium bicarbonate

triethylbenzylammonium chloride

Carcinoma, Non-Small-Cell Lung

English 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-[(18)F]fluoropropyl)-DL-tryptophan ([(18)F]2-FPTRP) and 5-(3-[(18)F]fluoro-propyl)-DL-tryptophan ([(18)F]5-FPTRP). Standard reference compounds and precursors were prepared by multi step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [(18)F]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 [(18)F]2-FPTRP comparable to the well established tyrosine analog O-(2-[(18)F]fluroethyl)-L-tyrosine ([(18)F]FET). Radiometabolite studies showed no evidence of involvement of a biotransformation step in tumor accumulation.

Language

English

Open access status

closed

Identifiers

DOI 10.1016/j.ejmech.2013.10.054
PMID 24239624

Persistent URL

https://sonar.ch/global/documents/180951

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