14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid (FTHA): Evaluation in mouse of a new probe of myocardial utilization of long chain fatty acids

Timothy R DeGrado, H. H. Coenen, G. Stocklin

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Abstract

14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid (FTHA) is a new radiolabeled long-chain fatty acid (LCFA) analog designed to undergo metabolic trapping subsequent to its commitment to the β-oxidation pathway. Sulfur-substitution at the sixth carbon of FTHA causes a prolonging of myocardial clearance half-time (T( 1/2 ) ~ 2 hr) in mice with little diminution of myocardial uptake (39.8 ± 3.0% ID/g at 5 min). Heart-to-blood ratios were 20 ± 6 and 82 ± 16 at 1 and 60 min, respectively. In contrast, the 3-thia analog, 13(R,S)-[18F]-fluoro-3-thia-hexadecanoic acid, showed lower uptake and poor retention by heart. Myocardial uptake of FTHA was reduced by 81% (p < 10-5) and 87% (p < 5 x 10-4) in mice pretreated with the carnitine palmitoyltransferase I inhibitor, 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA) at 1 and 60 min, respectively. Radioanalytical studies showed the major metabolic fate of FTHA in control and POCA treated myocardium to be unidentified metabolite(s) that bind to tissue protein. Smaller amounts of 18F radioactivity were present in myocardium as complex lipids, fatty acid, and unidentified soluble metabolites. The results indicate metabolic trapping of FTHA in myocardium subsequent to its entry into the mitochondrion and encourage its further evaluation as a PET tracer of myocardial LCFA utilization.

Original languageEnglish (US)
Pages (from-to)1888-1896
Number of pages9
JournalJournal of Nuclear Medicine
Volume32
Issue number10
StatePublished - 1991
Externally publishedYes

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Fatty Acids
Ethylene Oxide
Myocardium
Carnitine O-Palmitoyltransferase
Hairless Mouse
Palmitic Acid
Sulfur
Radioactivity
Mitochondria
Carbon
margaric acid
Lipids
Proteins

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

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14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid (FTHA) : Evaluation in mouse of a new probe of myocardial utilization of long chain fatty acids. / DeGrado, Timothy R; Coenen, H. H.; Stocklin, G.

In: Journal of Nuclear Medicine, Vol. 32, No. 10, 1991, p. 1888-1896.

Research output: Contribution to journalArticle

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abstract = "14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid (FTHA) is a new radiolabeled long-chain fatty acid (LCFA) analog designed to undergo metabolic trapping subsequent to its commitment to the β-oxidation pathway. Sulfur-substitution at the sixth carbon of FTHA causes a prolonging of myocardial clearance half-time (T( 1/2 ) ~ 2 hr) in mice with little diminution of myocardial uptake (39.8 ± 3.0{\%} ID/g at 5 min). Heart-to-blood ratios were 20 ± 6 and 82 ± 16 at 1 and 60 min, respectively. In contrast, the 3-thia analog, 13(R,S)-[18F]-fluoro-3-thia-hexadecanoic acid, showed lower uptake and poor retention by heart. Myocardial uptake of FTHA was reduced by 81{\%} (p < 10-5) and 87{\%} (p < 5 x 10-4) in mice pretreated with the carnitine palmitoyltransferase I inhibitor, 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA) at 1 and 60 min, respectively. Radioanalytical studies showed the major metabolic fate of FTHA in control and POCA treated myocardium to be unidentified metabolite(s) that bind to tissue protein. Smaller amounts of 18F radioactivity were present in myocardium as complex lipids, fatty acid, and unidentified soluble metabolites. The results indicate metabolic trapping of FTHA in myocardium subsequent to its entry into the mitochondrion and encourage its further evaluation as a PET tracer of myocardial LCFA utilization.",
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