Efficient automated syntheses of high specific activity 6-[18F]fluorodopamine using a diaryliodonium salt precursor

Kiel D. Neumann, Linlin Qin, Amy L. Vavere, Bin Shen, Zheng Miao, Frederick T. Chin, Barry L. Shulkin, Scott E. Snyder, Stephen G. Dimagno

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

6-[18F]Fluorodopamine (6-[18F]F-DA) is a positron emission tomography radiopharmaceutical used to image sympathetic cardiac innervation and neuroendocrine tumors. Imaging with 6-[18F]F-DA is constrained, in part, by the bioactivity and neurotoxicity of 6-[19F]fluorodopamine. Furthermore, routine access to this radiotracer is limited by the inherent difficulty of incorporation of [18F]fluoride into electron-rich aromatic substrates. We describe the simple and direct preparation of high specific activity (SA) 6-[18F]F-DA from no-carrier-added (n.c.a.) [18F]fluoride. Incorporation of n.c.a. [18F]fluoride into a diaryliodonium salt precursor was achieved in 50-75% radiochemical yields (decay corrected to end of bombardment). Synthesis of 6-[18F]F-DA on the IBA Synthera® and GE TRACERlab FX-FN automated platforms gave 6-[18F]F-DA in >99% chemical and radiochemical purities after HPLC purification. The final non-corrected yields of 6-[18F]F-DA were 25 ± 4% (n = 4, 65 min) and 31 ± 6% (n = 3, 75 min) using the Synthera and TRACERlab modules, respectively. Efficient access to high SA 6-[18F]F-DA from a diaryliodonium salt precursor and n.c.a. [18F]fluoride is provided by a relatively subtle change in reaction conditions - replacement of a polar aprotic solvent (acetonitrile) with a relatively nonpolar solvent (toluene) during the critical radiofluorination reaction. Implementation of this process on common radiochemistry platforms should make 6-[18F]F-DA readily available to the wider imaging community.

Original languageEnglish (US)
Pages (from-to)30-34
Number of pages5
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2016

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Fluorides
Salts
Radiochemistry
Imaging techniques
Heart Neoplasms
Positron emission tomography
Neuroendocrine Tumors
Radiopharmaceuticals
Toluene
Bioactivity
Positron-Emission Tomography
Purification
Tumors
High Pressure Liquid Chromatography
Electrons
6-fluorodopamine
Substrates

Keywords

  • 6-[F]fluorodopamine
  • diaryliodonium salts
  • emission computed tomography
  • fluorine-18
  • positron emission tomography

ASJC Scopus subject areas

  • Analytical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Drug Discovery
  • Radiology Nuclear Medicine and imaging
  • Biochemistry

Cite this

Efficient automated syntheses of high specific activity 6-[18F]fluorodopamine using a diaryliodonium salt precursor. / Neumann, Kiel D.; Qin, Linlin; Vavere, Amy L.; Shen, Bin; Miao, Zheng; Chin, Frederick T.; Shulkin, Barry L.; Snyder, Scott E.; Dimagno, Stephen G.

In: Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 59, No. 1, 01.01.2016, p. 30-34.

Research output: Contribution to journalArticle

Neumann, KD, Qin, L, Vavere, AL, Shen, B, Miao, Z, Chin, FT, Shulkin, BL, Snyder, SE & Dimagno, SG 2016, 'Efficient automated syntheses of high specific activity 6-[18F]fluorodopamine using a diaryliodonium salt precursor', Journal of Labelled Compounds and Radiopharmaceuticals, vol. 59, no. 1, pp. 30-34. https://doi.org/10.1002/jlcr.3367
Neumann, Kiel D. ; Qin, Linlin ; Vavere, Amy L. ; Shen, Bin ; Miao, Zheng ; Chin, Frederick T. ; Shulkin, Barry L. ; Snyder, Scott E. ; Dimagno, Stephen G. / Efficient automated syntheses of high specific activity 6-[18F]fluorodopamine using a diaryliodonium salt precursor. In: Journal of Labelled Compounds and Radiopharmaceuticals. 2016 ; Vol. 59, No. 1. pp. 30-34.
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abstract = "6-[18F]Fluorodopamine (6-[18F]F-DA) is a positron emission tomography radiopharmaceutical used to image sympathetic cardiac innervation and neuroendocrine tumors. Imaging with 6-[18F]F-DA is constrained, in part, by the bioactivity and neurotoxicity of 6-[19F]fluorodopamine. Furthermore, routine access to this radiotracer is limited by the inherent difficulty of incorporation of [18F]fluoride into electron-rich aromatic substrates. We describe the simple and direct preparation of high specific activity (SA) 6-[18F]F-DA from no-carrier-added (n.c.a.) [18F]fluoride. Incorporation of n.c.a. [18F]fluoride into a diaryliodonium salt precursor was achieved in 50-75{\%} radiochemical yields (decay corrected to end of bombardment). Synthesis of 6-[18F]F-DA on the IBA Synthera{\circledR} and GE TRACERlab FX-FN automated platforms gave 6-[18F]F-DA in >99{\%} chemical and radiochemical purities after HPLC purification. The final non-corrected yields of 6-[18F]F-DA were 25 ± 4{\%} (n = 4, 65 min) and 31 ± 6{\%} (n = 3, 75 min) using the Synthera and TRACERlab modules, respectively. Efficient access to high SA 6-[18F]F-DA from a diaryliodonium salt precursor and n.c.a. [18F]fluoride is provided by a relatively subtle change in reaction conditions - replacement of a polar aprotic solvent (acetonitrile) with a relatively nonpolar solvent (toluene) during the critical radiofluorination reaction. Implementation of this process on common radiochemistry platforms should make 6-[18F]F-DA readily available to the wider imaging community.",
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AU - Shen, Bin

AU - Miao, Zheng

AU - Chin, Frederick T.

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