Synthesis and animal studies of L-para-(/sup 18/F)-fluorophenyl-alanine as probe for in vivo cerebral protein synthesis
For the quantitation of cerebral protein synthesis in man by dynamic PET studies, fluorine-18 analogues seem superior to carbon-11 labeled substrates with respect to half-life and interference of amino acid metabolism giving rise to reutilization. Therefore, para- and ortho- /sup 18/F- fluorophenylalanine were prepared to study its metabolism in neuronal tissue. A labeling method was developed using direct electrophilic fluorination with (/sup 18/F)-F/sub 2/. Reaction of fluorine with L-phenylalanine in CF/sub 3/CO/sub 2/H at O/sup 0/C yielded 12-15% of ortho- and 6-8% of para-/sup 18/F-flurorophenylalanine. Isolation of the isomers was achieved by means of repeated RP-HPLC. The specific activity was about 2 Ci/mmole at 100 min after EOB. Both compounds showed a pharmacokinetic behaviour in mice after i.v. injection typical for natural amino acids. The accumulation in mice brain tissue reaches a plateau value after 5 min with 1.7% of the injected dose/g for para (2.5% in gerbils) and 2% for ortho. In a pilot study, about 1 mCi of p-/sup 18/F-phenylalanine was coinjected with 0.3 mCi (100 Ci/mmole) /sup 3/H-phenylalanine into the femoral vein of halothane-anesthetized Mongolian gerbils. The distribution obtained autoradiographyically in 20 ..mu..m sections of the frozen brain of an animal after 45 min revealed a similar pattern for both compounds indicating protein synthesis. In a parallel study 3-/sup 14/C-para-fluorophenylalanine was used to determine the chemical form of radioactivity in brain by means of HPLC. After 45 minutes, 7% of total brain activity was found as free amino acid and 60% was incorporated into proteins.
- Research Organization:
- Institut fur Chemie 1, Kernforschungsanlage Julich GmbH
- OSTI ID:
- 7033443
- Report Number(s):
- CONF-850611-; TRN: 87-010560
- Journal Information:
- J. Nucl. Med.; (United States), Vol. 26:5; Conference: 32. annual meeting of the Society of Nuclear Medicine, Houston, TX, USA, 2 Jun 1985
- Country of Publication:
- United States
- Language:
- English
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550501* - Metabolism- Tracer Techniques