Preparation and preliminary tissue studies of optically active 11C-d- and l-phenylalanine

Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds

“…213,288 On the other hand, [3-11 C]phenylalanine was prepared by 11 C-alkylation either via condensation reaction of [ 11 C]benzaldehyde with 2-aryl-5-oxazolone 342, 343 and by 1 1 C -b e n z y l a t i o n o f c o m m e r c i a l l y a v a i l a b l e N -(diphenylmethylene)glycine ester by applying a phase-transfer reaction/catalysis. 217,344−346 Also, the biosynthetic/enzyme approach was used either for the resolution of racemic D,L-[1-11 C]phenylalanine 215,272,345 (which was later replaced by chiral HPLC) or for the preparation of pure L-[1-11 C]phenylalanine 343,347 starting from the corresponding 11 Clabeled precursor. Considerable progress has been made in t h e e n a n t i o s e l e c t i v e p r e p a r a t i o n o f L -[ 3 -1 1 C ]phenylalanine, 346,347 and 11 C-radiolabeled amino acids at the 3-carbon during the last three decades.…”

“… Phenylalanine has one of the highest brain uptake indexes among amino acids . Although it has good potential for investigating protein synthesis rates in vivo by PET, only limited in vivo studies have been performed using this 11 C-labeled amino acid. − One reason might be its peripheral metabolism to tyrosine and intense competition with tyrosine and methionine for the same transport system localized in the endothelium of the brain capillaries with consequent complications for tracer kinetic modeling. The second reason is that until recently, no automated procedure has been available for reliable production of [ 11 C]­phenylalanine due to complex multistep syntheses or low RCYs after isolation and purification of l -enantiomer …”

“…[ 11 C]­Phenylalanine has been labeled at the 1 - (the carboxyl ) and 3 -carbon positions. , Racemic carboxyl-labeled d , l -[ 1 - 11 C]­phenylalanine was prepared by a modified Bücherer–Strecker synthesis using [ 11 C]­cyanide ,, as a radiolabeling agent and by 11 C-carboxylation of the activated α-lithioisonitrile precursor with [ 11 C]­CO 2 followed by acid hydrolysis of the intermediate. , On the other hand, [ 3 - 11 C]­phenylalanine was prepared by 11 C-alkylation either via condensation reaction of [ 11 C]­benzaldehyde with 2 -aryl- 5 -oxazolone , and by 11 C-benzylation of commercially available N -( diphenylmethylene )­glycine ester by applying a phase-transfer reaction/catalysis. ,− Also, the biosynthetic/enzyme approach was used either for the resolution of racemic d , l -[ 1 - 11 C]­phenylalanine ,, (which was later replaced by chiral HPLC) or for the preparation of pure l -[ 1 - 11 C]­phenylalanine , starting from the corresponding 11 C-labeled precursor. Considerable progress has been made in the enantioselective preparation of l -[ 3- 11 C]­phenylalanine, , and 11 C-radiolabeled amino acids at the 3 -carbon during the last three decades. ,− In this regard, Pekošak et al .…”

“…However, the image lacks a precise interpretation of the whole-body distribution. 211,341 Racemic carboxyl-labeled D,L-[1- 11 C]phenylalanine was prepared by a modified Bucherer−Strecker synthesis using [ 11 C]cyanide 212,215,287 as a radiolabeling agent and by 11 Ccarboxylation of the activated α-lithioisonitrile precursor with [ 11 C]CO 2 followed by acid hydrolysis of the intermediate. 213,288 On the other hand, [3-11 C]phenylalanine was prepared by 11 C-alkylation either via condensation reaction of [ 11 C]benzaldehyde with 2-aryl-5-oxazolone 342, 343 and by 1 1 C -b e n z y l a t i o n o f c o m m e r c i a l l y a v a i l a b l e N -(diphenylmethylene)glycine ester by applying a phase-transfer reaction/catalysis.…”

Criteria for the tracer kinetic measurement of cerebral protein synthesis in humans with positron emission tomography

“…Another factor that affects the level of background activity from metabolism is the branching fraction (the ratio of lCRPS/metabolism) through these competitive pathways. Results are shown in states in which subjects (1) fast for about 8 hours, ( 2 ) fast for about 8 hours and are then given a load dose of oral glucose (I to 2 hours before the study), and (3) are fed a carbohydrate meal 1 to 2 hours before the study plus a supplement of oral glucose 30 minutes to 1 hour prior to the study. Studies performed in the fasted state 'Studies in two separate subjects in the same dietary state but having different levels of plasma leucine (shown in the Table) and glucose (top subject = 98 mgllO0 ml; bottom subject = 130 mg/IOO ml).…”