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

Journal Article · Fri Feb 01 00:00:00 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), Vol. 34:2; ISSN 0022-2623
• Country of Publication: United States
• Language: English

Related Subjects

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