Synthesis and tissue distribution of fluorine-18 labeled trifluorohexadecanoic acids. Considerations in the development of metabolically blocked myocardial imaging agents
- Univ. of Illinois, Urbana, IL (United States)
- Washington Univ. School of Medicine, St. Louis, MO (United States)
A versatile method for the synthesis of trifluoro fatty acids, potential metabolically blocked myocardial imaging agents, has been developed. Two trifluorohexadecanoic (palmitic) acids have been prepared [6,6,16-trifluorohexadecanoic acid (I) and 7,7,16-trifluorohexadecanoic acid (II)], each of which bears two of the fluorine atoms as a gem-difluoromethylene unit on the fatty acid chain (at C-6 or C-7) and the third at the [omega] (C-16) position. The metabolic stability of carbon-fluorine bonds suggests the gem-difluoro group may block the [beta]-oxidation pathway, while the terminal fluorine could be the site for labeling with fluorine-18. The convergent synthetic approach utilizes a 2-lithio-1,3-dithiane derived from 10-undecenal or 9-decenal, which is alkylated with the OBO (oxabicyclooctyl) ester of 5-bromopentanoic acid or 6-bromohexanoic acid, respectively. Hydroboration-oxidation and alcohol protection are followed by halofluorination to convert the 1,3-dithiane system to a gem-difluoro group. The third fluorine is introduced by fluoride ion displacement of a trifluoromethanesulfonate. This synthesis is adapted to the labeling of these trifluoro fatty acids with the short-lived radionuclide fluorine-18 (t[sub 1/2] = 110 min), with the third fluorine introduced as fluoride ion in the penultimate step. The radiochemical syntheses proceed in 3-34% radiochemical yield (decay corrected), with an overall synthesis and purification time of 90 min. Tissue distribution studies in rats were performed with I and II, as well as with 16-[[sup 18]F]fluoropalmitic acid (III), [[sup 11]C]palmitic acid, and [[sup 11]C]octanoic acid. The heart uptake of the fluoropalmitic acids decreases with substitution, the 2-min activity level for 16-fluoropalmitic acid being 65% and that for both 6,6,16-and 7,7,17-trifluoropalmitic acids being 30% that of palmitic acid.
- DOE Contract Number:
- FG02-84ER60218
- OSTI ID:
- 5492848
- Journal Information:
- Bioconjugate Chemistry; (United States), Vol. 1:4; ISSN 1043-1802
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
FLUORINE 18
CHEMICAL REACTIONS
HEXADECANOIC ACID
FLUORINATION
LABELLING
MYOCARDIUM
BIOMEDICAL RADIOGRAPHY
RADIOPHARMACEUTICALS
CHEMICAL PREPARATION
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
DIAGNOSTIC TECHNIQUES
DRUGS
FLUORINE ISOTOPES
HALOGENATION
HEART
HOURS LIVING RADIOISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MEDICINE
MONOCARBOXYLIC ACIDS
MUSCLES
NANOSEC LIVING RADIOISOTOPES
NUCLEAR MEDICINE
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RADIOISOTOPES
RADIOLOGY
SYNTHESIS
400703* - Radiochemistry & Nuclear Chemistry- Radioisotope Production
550601 - Medicine- Unsealed Radionuclides in Diagnostics
560160 - Radionuclide Effects
Kinetics
& Toxicology