1. Synthesis and biological evaluation of 18F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging.
- Author
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Chiotellis, Aristeidis, Mu, Linjing, Müller, Adrienne, Selivanova, Svetlana V., Keller, Claudia, Schibli, Roger, Krämer, Stefanie D., and Ametamey, Simon M.
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TRYPTOPHAN oxygenase , *POSITRON emission tomography , *MOLECULAR probes , *IMAGING of cancer , *FLUORINE compounds , *RADIOLABELING , *CHEMICAL synthesis , *IN vitro studies - Abstract
Abstract: 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-[18F]fluoropropyl)-dl-tryptophan ([18F]2-FPTRP) and 5-(3-[18F]fluoro-propyl)-dl-tryptophan ([18F]5-FPTRP). Standard reference compounds and precursors were prepared by multi step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [18F]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 [18F]2-FPTRP comparable to the well established tyrosine analog O-(2-[18F]fluroethyl)-l-tyrosine ([18F]FET). Radiometabolite studies showed no evidence of involvement of a biotransformation step in tumor accumulation. [Copyright &y& Elsevier]
- Published
- 2013
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