@entity470 ( @entity470 ), upregulated in many @entity5 types, have been a target for therapeutic development and molecular imaging. The objective of this study was to evaluate the distribution and metabolic characteristics of fluorine-18 labeled anilinoquinazolines as potential imaging agents for @entity470 @entity669 kinase expression. @entity8984 labeled fluoronitrobenzenes were prepared by reaction of @entity972 cryptand [(18)F]fluoride with 1,2- and 1,4-dinitrobenzenes, and 3-nitro-N,N,N-trimethylanilinium triflate in 5min. Decay-corrected radiochemical yields of [(18)F]fluoride incorporation into the @entity6836 -aromatic compounds were 81  2%, 44  4% and 77  5% (n=3-5) for the 2-, 3- and 4-fluoro isomers, respectively. @entity8951 reduction to the corresponding [(18)F]fluoroanilines was achieved with greater than 80% conversion in 5min. Coupling of [(18)F]fluoroaniline-hydrochlorides to 6,7-dimethoxy-4-chloro-quinazoline gave the corresponding 6,7-dimethoxy-4-(2-, 3- and 4-[(18)F]fluoroanilino)quinazolines in 31  5%, 17  2% and 55  2% radiochemical yield, respectively, while coupling to the 6,7-diethoxy-4-chloro-quinazoline produced 6,7-diethoxy-4-(2-, 3- and 4-[(18)F]fluoroanilino)quinazolines in 19  6%, 9  3% and 36  6% radiochemical yield, respectively, in 90min to end of synthesis from [(18)F]fluoride. Biodistribution of 2- and 4-[(18)F]fluoroanilinoquinazolines was conducted in @entity5 -bearing @entity19 (MDA-MB-435 and MDA-MB-468 xenografts). @entity5 uptake (<1% injected dose per gram (ID/g) of tissue up to 3h postinjection of the radiotracers) was observed. High bone uptake (5-15% ID/g) was noted with the 4-[(18)F]fluoroanilinoquinazolines. The metabolic stabilities of radiolabeled @entity70280 were further evaluated by incubation with @entity1 female cryopreserved isolated hepatocytes. @entity528 was observed by radio-TLC, whereas, the 2- and 3-[(18)F]fluoroaniline derivatives were significantly more stable, up to 2h, corroborating the in vivo biodistribution studies. para-Substituted [(18)F]fluoroanilines, a common structural motif in radiopharmaceuticals, are highly susceptible to metabolic degradation.

Metabolic stability of 6,7-dialkoxy-4-(2-, 3- and 4-[18F]fluoroanilino)quinazolines, potential XXXX imaging probes.

@entity8984 :: ('CHEBI:36939', 'Chemical') :: ['Fluorine-18'] @entity1 :: ('9606', 'Species') :: ['human'] @entity70280 :: ('MESH:D011799', 'Chemical') :: ['quinazolines'] @entity470 :: ('1956', 'Gene') :: ['Epidermal growth factor receptors', 'EGFR'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'Low tumor'] @entity8951 :: ('MESH:C025364', 'Chemical') :: ['Sodium borohydride'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity6836 :: ('CHEBI:29785', 'Chemical') :: ['nitro'] @entity972 :: ('MESH:D011188', 'Chemical') :: ['potassium'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity528 :: ('MESH:D009410', 'Disease') :: ['Rapid degeneration of the 4-fluoro-substituted compounds to baseline polar metabolites']
@entity470 :: (1956,Gene) :: ['EGFR']
