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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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18-[18F]Fluoro-4-thia-palmitate

[18F]FTP
, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: December 22, 2010.

Chemical name:18-[18F]Fluoro-4-thia-palmitateimage 103058738 in the ncbi pubchem database
Abbreviated name:[18F]FTP
Synonym:
Agent category:Compound
Target:Fatty acid oxidation (FAO) enzymes
Target category:Enzyme
Method of detection:Positron emission tomography (PET)
Source of signal:18F
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
  • Checkbox Non-primate non-rodent mammals
Click on the above structure for additional information in PubChem.

Background

[PubMed]

β-Oxidation of long-chain fatty acids is the major (60%–80%) aerobic process for energy production in the heart, liver, and skeletal muscle. Abnormalities of fatty acid oxidation (FAO) are associated with several cardiovascular diseases, neurodegeneration, fatty liver, and diabetes (1-5). Myocardium has a high mitochondrial content because of high energy usage. Carnitine palmitoyltransferases (CPT1 and CPT2) mediate transfer of fatty acids into the mitochondrial matrix for β-oxidation (6, 7). Various radiolabeled, thia-substituted, fatty acid analogs have been found to be metabolically trapped in the myocardial mitochondria (8-10). 4-Thia fatty acids are oxidized in the mitochondria to 4-thia-enoyl-CoAs, which cannot be further metabolized and trapped (protein-bound) in the mitochondria. DeGrado et al. (11, 12) have synthesized 18-[18F]fluoro-4-thia-palmitate ([18F]FTP) for evaluation as a positron emission tomography (PET) agent of FAO.

Synthesis

[PubMed]

[18F]FTP was prepared as described by DeGrado et al. (13). [18F]Fluoride/Kryptofix 2.2.2/K2CO3 and methyl-16-iodo-4-thia-hexadecanoate were heated in acetonitrile for 15 min at 85°C, followed by hydrolysis with KOH for 4 min at 90°C. [18F]FTP was purified with high-performance liquid chromatography with radiochemical yields of 25%–60% (decay-corrected) and a radiochemical purity of >99%. Specific activity of [18F]FTP was >74.0 GBq/µmol (2.0 Ci/µmol) at the end of synthesis.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

DeGrado et al. (13) performed perfusion studies with isolated rat hearts (n = 5 per group) in normoxic (95% O2) and hypoxic (35% O2) conditions. [18F]FTP was administered at the aortic root. The fractional tracer metabolic rate (FRFTP) was 1.45 ± 0.39 mL/min per g under normoxic conditions and 0.73 ± 0.16 mL/min per g under hypoxic conditions. There was a reduction of 50% in the hypoxic group relative to the normoxic group. The FRFTP was ~60% of the palmitate oxidation rate in these two conditions.

Animal Studies

Rodents

[PubMed]

DeGrado et al. (12) performed ex vivo biodistribution studies of [18F]FTP in rats. [18F]FTP accumulated mainly in the heart, liver, bone, and kidney with 0.32 ± 0.17% injected dose (ID)/g, 1.15 ± 0.16% ID/g, 0.24 ± 0.07% ID/g, and 0.25 ± 0.04% ID/g, respectively, at 30 min after injection. Retention of [18F]FTP in the heart was moderate with 0.17 ± 0.05% ID/g at 120 min, whereas there was a slight washout in the liver and kidney. Bone accumulation was approximately one-fold higher at 120 min. Pretreatment with the CPT1 inhibitor etomoxir (40 mg/kg, 120 min before [18F]FTP injection) reduced the radioactivity level in the heart by 82% at 30 min after injection with little inhibition in the other organs. Folch-type analysis of the excised hearts showed that 80% of [18F]FTP radioactivity was protein-bound. Pretreatment with etomoxir reduced the protein-bound radioactivity to 10%. The heart/blood, heart/lung, heart/brain, and heart/muscle ratios were 7, 3, 10, and 10, respectively, at 120 min after injection.

Other Non-Primate Mammals

[PubMed]

Whole-body PET imaging in two swine showed that [18F]FTP accumulated mainly in the heart, liver, and kidneys with low accumulation in the bone over an imaging period of 3 h (13). Good myocardial images were observed at 10–20 min after injection with little interference from the lung and liver. Myocardium/blood and myocardium/lung ratios were 7 and 8, respectively, at 20 min after injection. Myocardium clearance half-time of radioactivity was 5 h, whereas the clearance half-time was 50 min for the liver.

Non-Human Primates

[PubMed]

No publication is currently available.

Human Studies

[PubMed]

No publication is currently available.

NIH Support

R01 HL63371, R01 CA108620, HL54882

References

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Stanley W.C., Recchia F.A., Lopaschuk G.D. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev. 2005;85(3):1093–129. [PubMed: 15987803]
2.
Bergmann S.R., Herrero P., Sciacca R., Hartman J.J., Rubin P.J., Hickey K.T., Epstein S., Kelly D.P. Characterization of altered myocardial fatty acid metabolism in patients with inherited cardiomyopathy. J Inherit Metab Dis. 2001;24(6):657–74. [PubMed: 11768585]
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Liu Y. Fatty acid oxidation is a dominant bioenergetic pathway in prostate cancer. Prostate Cancer Prostatic Dis. 2006;9(3):230–4. [PubMed: 16683009]
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You M., Crabb D.W. Recent advances in alcoholic liver disease II. Minireview: molecular mechanisms of alcoholic fatty liver. Am J Physiol Gastrointest Liver Physiol. 2004;287(1):G1–6. [PubMed: 15194557]
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Stanley W.C., Lopaschuk G.D., McCormack J.G. Regulation of energy substrate metabolism in the diabetic heart. Cardiovasc Res. 1997;34(1):25–33. [PubMed: 9217869]
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Jogl G., Hsiao Y.S., Tong L. Structure and function of carnitine acyltransferases. Ann N Y Acad Sci. 2004;1033:17–29. [PubMed: 15591000]
7.
Bonnefont J.P., Djouadi F., Prip-Buus C., Gobin S., Munnich A., Bastin J. Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects. Mol Aspects Med. 2004;25(5-6):495–520. [PubMed: 15363638]
8.
Taylor M., Wallhaus T.R., Degrado T.R., Russell D.C., Stanko P., Nickles R.J., Stone C.K. An evaluation of myocardial fatty acid and glucose uptake using PET with [18F]fluoro-6-thia-heptadecanoic acid and [18F]FDG in Patients with Congestive Heart Failure. J Nucl Med. 2001;42(1):55–62. [PubMed: 11197981]
9.
DeGrado T.R., Wang S., Rockey D.C. Preliminary evaluation of 15-[18F]fluoro-3-oxa-pentadecanoate as a PET tracer of hepatic fatty acid oxidation. J Nucl Med. 2000;41(10):1727–36. [PubMed: 11038005]
10.
Stone C.K., Pooley R.A., DeGrado T.R., Renstrom B., Nickles R.J., Nellis S.H., Liedtke A.J., Holden J.E. Myocardial uptake of the fatty acid analog 14-fluorine-18-fluoro-6-thia-heptadecanoic acid in comparison to beta-oxidation rates by tritiated palmitate. J Nucl Med. 1998;39(10):1690–6. [PubMed: 9776270]
11.
DeGrado T.R., Bhattacharyya F., Pandey M.K., Belanger A.P., Wang S. Synthesis and preliminary evaluation of 18-(18)F-fluoro-4-thia-oleate as a PET probe of fatty acid oxidation. J Nucl Med. 2010;51(8):1310–7. [PubMed: 20660391]
12.
DeGrado T.R., Kitapci M.T., Wang S., Ying J., Lopaschuk G.D. Validation of 18F-fluoro-4-thia-palmitate as a PET probe for myocardial fatty acid oxidation: effects of hypoxia and composition of exogenous fatty acids. J Nucl Med. 2006;47(1):173–81. [PubMed: 16391202]
13.
DeGrado T.R., Wang S., Holden J.E., Nickles R.J., Taylor M., Stone C.K. Synthesis and preliminary evaluation of (18)F-labeled 4-thia palmitate as a PET tracer of myocardial fatty acid oxidation. Nucl Med Biol. 2000;27(3):221–31. [PubMed: 10832078]

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