Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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Synthesis and biodistribution of 18F-labeled α-, β- and ω-fluorohexadecanoic acid

  • Lee, Yun-Sang (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Kim, Young Joo (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Cheon, Gi Jeong (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Jeong, Jae Min (Department of Nuclear Medicine, Seoul National University College of Medicine)
  • Received : 2018.12.07
  • Accepted : 2018.12.19
  • Published : 2018.12.30
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Abstract

${\omega}-[^{18}F]$-Fluorohexadecanoic acid (FHA) has been used for imaging of fatty acid metabolism of myocardium. To increase retention of radiolabeled fatty acid by blocking ${\beta}$-oxidation, methyl branched analogues have been used. In this experiment, we tried to synthesize 18F-labeled ${\alpha}-$, ${\beta}-$ and ${\omega}-FHA$ for imaging of the myocardial fatty acid metabolism. We synthesized ${\alpha}-$, ${\beta}-$ and ${\omega}$-mesylated methyl hexadecanoates and labeled with $^{18}F$ by reacting with $[^{18}F]$TBAF in acetonitrile at $80^{\circ}C$ for 10 min. Methyl ester group was removed by 1 M NaOH at $80^{\circ}C$ for 5 min. The yields of ${\alpha}-[^{18}F]$ and ${\omega}-[^{18}F]FHA$ were 25.5 and 45.5%, respectively [EOS]. However, ${\beta}-[^{18}F]FHA$ was not labeled at all due to a fast elimination reaction. The biodistribution study in ICR-mice showed that ${\omega}-[^{18}F]FHA$ has higher myocardial uptake and lower liver uptake than ${\alpha}-[^{18}F]FHA$. The electron-withdrawing effect of fluorine at ${\alpha}-$ position is believed to be the major factor affecting the biodistribution.

Keywords

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Figure 1. Chemical structures of 18F-labeled α-, β- and ω-FHA

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Figure 2. Synthesis of 18F-labeling precursors

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Figure 3. 18F-labeling

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Figure 4. Purification of α- and ω-[18F]FHA

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Figure 5. TLC chromatogram of α- and ω-[18F]FHA

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Figure 6. Elimination reaction in the synthesis of β-[18F]FHA and the molecular ion peak of elimination product from mass spectrometer data

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Figure 7. Biodistribution of α- and ω-[18F]FHA

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Figure 8. PET images of α- and ω-[18F]FHA in dogs. (A) Short axis static view at 3 min of α-[18F]FHA (B) Short axis static view at 3 min of ω-[18F]FHA

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