Synthesis of [11C]PBR06 and [18F]PBR06 as agents for positron emission tomographic (PET) imaging of the translocator protein (TSPO)

Min Wang, Mingzhang Gao, Kathy Miller, Qi-Huang Zheng

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The translocator protein 18 kDa (TSPO) is an attractive target for molecular imaging of neuroinflammation and tumor progression. [ 18F]PBR06, a fluorine-18 labeled form of PBR06, is a promising PET TSPO radioligand originally developed at NIMH. [11C]PBR06, a carbon-11 labeled form of PBR06, was designed and synthesized for the first time. The standard PBR06 was synthesized from 2,5-dimethoxybenzaldehyde in three steps with 71% overall chemical yield. The radiolabeling precursor desmethyl-PBR06 was synthesized from 2-hydroxy-5-methoxybenzaldehyde in five steps with 12% overall chemical yield. The target tracer [11C]PBR06 was prepared by O-[11C]methylation of desmethyl-PBR06 with [ 11C]CH3OTf in CH3CN at 80 °C under basic condition and isolated by HPLC combined with SPE purification with 40-60% decay corrected radiochemical yield and 222-740 GBq/μmol specific activity at EOB. On the similar grounds, [18F]PBR06 was also designed and synthesized. The previously described Br-PBR06 precursor was synthesized from 2,5-dimethoxybenzaldehyde in two steps with 78% overall chemical yield. A new radiolabeling precursor tosyloxy-PBR06, previously undescribed tosylate congener of PBR06, was designed and synthesized from ethyl 2-hydroxyacetate, 4-methylbenzene-1-sulfonyl chloride, and N-(2,5-dimethoxybenzyl)-2- phenoxyaniline in four steps with 50% overall chemical yield. [ 18F]PBR06 was prepared by the nucleophilic substitution of either new tosyloxy-PBR06 precursor or known Br-PBR06 precursor in DMSO at 140 °C with K[18F]F/Kryptofix 2.2.2 for 15 min and HPLC combined with SPE purification in 20-60% decay corrected radiochemical yield, >99% radiochemical purity, 87-95% chemical purity, and 37-222 GBq/μmol specific activity at EOB. Radiosynthesis of [18F]PBR06 using new tosylated precursor gave similar radiochemical purity, and higher specific activity, radiochemical yield and chemical purity in comparison with radiosynthesis using bromine precursor.

Original languageEnglish
Pages (from-to)1331-1340
Number of pages10
JournalSteroids
Volume76
Issue number12
DOIs
StatePublished - Nov 2011

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Positrons
Electrons
Imaging techniques
Glycolates
Proteins
High Pressure Liquid Chromatography
National Institute of Mental Health (U.S.)
Bromine
Molecular Imaging
Purification
Fluorine
Dimethyl Sulfoxide
Methylation
Molecular imaging
Carbon
N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline
Tumors
Substitution reactions
Neoplasms

Keywords

  • [C]PBR06
  • [F]PBR06
  • Neuroinflammation imaging
  • Positron emission tomography (PET)
  • The translocator protein 18 kDa (TSPO)
  • Tumor imaging

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Molecular Biology
  • Organic Chemistry
  • Pharmacology

Cite this

Synthesis of [11C]PBR06 and [18F]PBR06 as agents for positron emission tomographic (PET) imaging of the translocator protein (TSPO). / Wang, Min; Gao, Mingzhang; Miller, Kathy; Zheng, Qi-Huang.

In: Steroids, Vol. 76, No. 12, 11.2011, p. 1331-1340.

Research output: Contribution to journalArticle

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abstract = "The translocator protein 18 kDa (TSPO) is an attractive target for molecular imaging of neuroinflammation and tumor progression. [ 18F]PBR06, a fluorine-18 labeled form of PBR06, is a promising PET TSPO radioligand originally developed at NIMH. [11C]PBR06, a carbon-11 labeled form of PBR06, was designed and synthesized for the first time. The standard PBR06 was synthesized from 2,5-dimethoxybenzaldehyde in three steps with 71{\%} overall chemical yield. The radiolabeling precursor desmethyl-PBR06 was synthesized from 2-hydroxy-5-methoxybenzaldehyde in five steps with 12{\%} overall chemical yield. The target tracer [11C]PBR06 was prepared by O-[11C]methylation of desmethyl-PBR06 with [ 11C]CH3OTf in CH3CN at 80 °C under basic condition and isolated by HPLC combined with SPE purification with 40-60{\%} decay corrected radiochemical yield and 222-740 GBq/μmol specific activity at EOB. On the similar grounds, [18F]PBR06 was also designed and synthesized. The previously described Br-PBR06 precursor was synthesized from 2,5-dimethoxybenzaldehyde in two steps with 78{\%} overall chemical yield. A new radiolabeling precursor tosyloxy-PBR06, previously undescribed tosylate congener of PBR06, was designed and synthesized from ethyl 2-hydroxyacetate, 4-methylbenzene-1-sulfonyl chloride, and N-(2,5-dimethoxybenzyl)-2- phenoxyaniline in four steps with 50{\%} overall chemical yield. [ 18F]PBR06 was prepared by the nucleophilic substitution of either new tosyloxy-PBR06 precursor or known Br-PBR06 precursor in DMSO at 140 °C with K[18F]F/Kryptofix 2.2.2 for 15 min and HPLC combined with SPE purification in 20-60{\%} decay corrected radiochemical yield, >99{\%} radiochemical purity, 87-95{\%} chemical purity, and 37-222 GBq/μmol specific activity at EOB. Radiosynthesis of [18F]PBR06 using new tosylated precursor gave similar radiochemical purity, and higher specific activity, radiochemical yield and chemical purity in comparison with radiosynthesis using bromine precursor.",
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