Synthesis of high specific activity (+)- and (-)-6-( sup 18 F)fluoronorepinephrine via the nucleophilic aromatic substitution reaction

Journal Article · Thu Jan 31 23:00:00 EST 1991 · Journal of Medicinal Chemistry; (USA)

DOI:https://doi.org/10.1021/jm00106a043· OSTI ID:5893387

Ding, Y S; Fowler, J S; Gatley, S J; Dewey, S L; Wolf, A P ^[1]

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1. Brookhaven National Laboratory, Upton, NY (USA)

The first example of a no-carrier-added {sup 18}F-labeled catecholamine, 6-({sup 18}F)fluoronorepinephrine (6-({sup 18}F)FNE), has been synthesized via nucleophilic aromatic substitution. The racemic mixture was resolved on a chiral HPLC column to obtain pure samples of (-)-6-({sup 18}F)FNE and (+)6-({sup 18}F)FNE. Radiochemical yields of 20% at the end of bombardment (EOB) for the racemic mixture (synthesis time 93 min), 6% for each enantiomer (synthesis time 128 min) with a specific activity of 2-5 Ci/mumol at EOB were obtained. Chiral HPLC peak assignment for the resolved enantiomers was achieved by using two independent methods: polarimetric determination and reaction with dopamine beta-hydroxylase. Positron emission tomography (PET) studies with racemic 6-({sup 18}F)FNE show high uptake and retention in the baboon heart. This work demonstrates that nucleophilic aromatic substitution by ({sup 18}F)fluoride ion is applicable to systems having electron-rich aromatic rings, leading to high specific activity radiopharmaceuticals. Furthermore, the suitably protected dihydroxynitrobenzaldehyde 1 may serve as a useful synthetic precursor for the radiosynthesis of other complex {sup 18}F-labeled radiotracers.

• OSTI ID: 5893387
• Journal Information: Journal of Medicinal Chemistry; (USA), Journal Name: Journal of Medicinal Chemistry; (USA) Vol. 34:2; ISSN JMCMA; ISSN 0022-2623
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
BABOONS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
CARDIOVASCULAR SYSTEM
CHEMICAL PREPARATION
CHROMATOGRAPHY
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DRUGS
EMISSION COMPUTED TOMOGRAPHY
FLUORINE 18
FLUORINE ISOTOPES
HEART
HOURS LIVING RADIOISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MONKEYS
NUCLEI
ODD-ODD NUCLEI
ORGANS
POSITRON COMPUTED TOMOGRAPHY
PRIMATES
RADIOISOTOPES
RADIOPHARMACEUTICALS
SEPARATION PROCESSES
SPECIFICITY
SYNTHESIS
TOMOGRAPHY
UPTAKE
VERTEBRATES