- Discovery of 7-[18F]Fluorotryptophan as a Novel Positron Emission Tomography (PET) Probe for the Visualization of Tryptophan Metabolism in Vivo
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Tryptophan and its metabolites are involved in different physiological and pathophysiological processes. Consequently, positron emission tomography (PET) tracers addressing tryptophan metabolic pathways should allow the detection of different pathologies like neurological disorders and cancer. Herein we report an efficient method for the preparation of fluorotryptophans labeled in different positions with 18F and their biological evaluation. 4-7-[18F]Fluorotryptophans ([18F]FTrps) were prepared according to a modified protocol of alcohol-enhanced Cu-mediated radiofluorination in 30-53% radiochemical yields. In vitro experiments demonstrated high cellular uptake of 4-7-[18F]FTrps in different tumor cell lines. 4, 5-, and 6-[18F]FTrps, although stable in vitro, suffered from rapid in vivo defluorination. In contrast, 7-[18F]FTrp demonstrated a high in vivo stability and enabled a clear delineation of serotonergic areas and melatonin-producing pineal gland in rat brains. Moreover 7-[18F]FTrp accumulated in different tumor xenografts in a chick embryo CAM model. Thus, 7-[18F]FTrp represents a highly promising PET probe for imaging of Trp metabolism.
- Zlatopolskiy, Boris D.,Zischler, Johannes,Sch?fer, Dominique,Urusova, Elizaveta A.,Guliyev, Mehrab,Bannykh, Olesia,Endepols, Heike,Neumaier, Bernd
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p. 189 - 206
(2018/02/10)
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- Mild, Aqueous α-Arylation of Ketones: Towards New Diversification Tools for Halogenated Metabolites and Drug Molecules
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The palladium-catalysed aqueous α-arylation of ketones was developed and tested for a large variety of reaction partners. These mild conditions enabled the coupling of aryl/alkyl-ketones with N-protected halotryptophans, heterocyclic haloarenes, and challenging base-sensitive compounds. The synthetic potential of this new methodology for the diversification of complex bioactive molecules was exemplified by derivatising prochlorperazine. The methodology is mild, aqueous and flexible, representing a means of functionalizing a wide range of halo-aromatics and therefore has the potential to be extended to complex molecule diversification.
- Marelli, Enrico,Renault, Yohann,Sharma, Sunil V.,Nolan, Steven P.,Goss, Rebecca J. M.
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p. 3832 - 3836
(2017/03/27)
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- Somatostatin analogs having a substituted tryptophyl residue in position eight
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Tetradecapeptides of the formula STR1 in which A represents L, D or DL 5- or 6- fluoro-, bromo-,chloro- or iodotryptophyl, or a therapeutically acceptable acid addition salt thereof, their preparation and intermediates for their preparation are disclosed. The tetradecapeptides are useful for inhibiting the release of growth hormone. Compositions and methods for their use also are disclosed.
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