Synthesis of 18F-Tetrafluoroborate via radiofluorination of boron trifluoride and evaluation in a murine C6-Glioma tumor model

Huailei Jiang, Aditya Bansal, Mukesh Pandey, Kah-Whye Peng, Lukkana Suksanpaisan, Stephen J Russell, Timothy R DeGrado

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The sodium/iodide symporter (NIS) is under investigation as a reporter for noninvasive imaging of gene expression. Although 18F-Tetrafluoroborate (18F-TFB, 18F-BF4-) has shown promise as a PET imaging probe for NIS, the current synthesis method using isotopic exchange gives suboptimal radiochemical yield and specific activity. The aim of this study was to synthesize 18F-TFB via direct radiofluorination on boron trifluoride (BF3) to enhance both labeling yield and specific activity and evaluation of specific activity influence on tumor uptake. Methods: An automated synthesis of 18F-TFB was developed whereby cyclotron-produced 18F-fluoride was trapped on a quaternary methyl ammonium anion exchange cartridge, then allowed to react with BF3 freshly preformulated in petroleum ether/tetrahydrofuran (50:1). The resultant 18F-TFB product was retained on the quaternary methyl ammonium anion exchange cartridge. After the cartridge was rinsed with tetrahydrofuran and water, 18F-TFB was eluted from the cartridge with isotonic saline, passing through 3 neutral alumina cartridges and a sterilizing filter. Preclinical imaging studies with 18F-TFB were performed in athymic mice bearing NIS-expressing C6-glioma subcutaneous xenografted tumors to determine the influence of specific activity on tumor uptake. Results: Under optimized conditions, 18F-TFB was synthesized in a radiochemical yield of 20.0% ± 0.7% (n 5 3, uncorrected for decay) and greater than 98% radiochemical purity in a synthesis time of 10 min. Specific activities of 8.84 ± 0.56 GBq/μmol (n 5 3) were achieved from starting 18F-fluoride radioactivities of 40-44 GBq. An avid uptake of 18F-TFB was observed in human NIS (hNIS)-expressing C6-glioma xenografts as well as expected NIS-mediated uptake in the thyroid and stomach. There was a positive correlation between the uptake of 18F-TFB in hNISexpressing tumor and specific activity. Conclusion: A rapid, practical, and high-specific-Activity synthesis of the NIS reporter probe 18F-TFB was achieved via direct radiofluorination on BF3 using an automated synthesis system. The synthesis of high-specific-Activity 18F-TFB should enable future clinical studies with hNIS gene reporter viral constructs.

Original languageEnglish (US)
Pages (from-to)1454-1459
Number of pages6
JournalJournal of Nuclear Medicine
Volume57
Issue number9
DOIs
StatePublished - Sep 1 2016

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Glioma
Fluorides
Ammonium Compounds
Anions
Neoplasms
Cyclotrons
Viral Genes
Aluminum Oxide
Reporter Genes
Heterografts
Nude Mice
Radioactivity
Stomach
Thyroid Gland
Gene Expression
boron trifluoride
Water
tetrahydrofuran

Keywords

  • F
  • Pet
  • Radiofluorination
  • Sodium/iodide symporter
  • Tetrafluoroborate

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Synthesis of 18F-Tetrafluoroborate via radiofluorination of boron trifluoride and evaluation in a murine C6-Glioma tumor model. / Jiang, Huailei; Bansal, Aditya; Pandey, Mukesh; Peng, Kah-Whye; Suksanpaisan, Lukkana; Russell, Stephen J; DeGrado, Timothy R.

In: Journal of Nuclear Medicine, Vol. 57, No. 9, 01.09.2016, p. 1454-1459.

Research output: Contribution to journalArticle

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title = "Synthesis of 18F-Tetrafluoroborate via radiofluorination of boron trifluoride and evaluation in a murine C6-Glioma tumor model",
abstract = "The sodium/iodide symporter (NIS) is under investigation as a reporter for noninvasive imaging of gene expression. Although 18F-Tetrafluoroborate (18F-TFB, 18F-BF4-) has shown promise as a PET imaging probe for NIS, the current synthesis method using isotopic exchange gives suboptimal radiochemical yield and specific activity. The aim of this study was to synthesize 18F-TFB via direct radiofluorination on boron trifluoride (BF3) to enhance both labeling yield and specific activity and evaluation of specific activity influence on tumor uptake. Methods: An automated synthesis of 18F-TFB was developed whereby cyclotron-produced 18F-fluoride was trapped on a quaternary methyl ammonium anion exchange cartridge, then allowed to react with BF3 freshly preformulated in petroleum ether/tetrahydrofuran (50:1). The resultant 18F-TFB product was retained on the quaternary methyl ammonium anion exchange cartridge. After the cartridge was rinsed with tetrahydrofuran and water, 18F-TFB was eluted from the cartridge with isotonic saline, passing through 3 neutral alumina cartridges and a sterilizing filter. Preclinical imaging studies with 18F-TFB were performed in athymic mice bearing NIS-expressing C6-glioma subcutaneous xenografted tumors to determine the influence of specific activity on tumor uptake. Results: Under optimized conditions, 18F-TFB was synthesized in a radiochemical yield of 20.0{\%} ± 0.7{\%} (n 5 3, uncorrected for decay) and greater than 98{\%} radiochemical purity in a synthesis time of 10 min. Specific activities of 8.84 ± 0.56 GBq/μmol (n 5 3) were achieved from starting 18F-fluoride radioactivities of 40-44 GBq. An avid uptake of 18F-TFB was observed in human NIS (hNIS)-expressing C6-glioma xenografts as well as expected NIS-mediated uptake in the thyroid and stomach. There was a positive correlation between the uptake of 18F-TFB in hNISexpressing tumor and specific activity. Conclusion: A rapid, practical, and high-specific-Activity synthesis of the NIS reporter probe 18F-TFB was achieved via direct radiofluorination on BF3 using an automated synthesis system. The synthesis of high-specific-Activity 18F-TFB should enable future clinical studies with hNIS gene reporter viral constructs.",
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author = "Huailei Jiang and Aditya Bansal and Mukesh Pandey and Kah-Whye Peng and Lukkana Suksanpaisan and Russell, {Stephen J} and DeGrado, {Timothy R}",
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AU - Jiang, Huailei

AU - Bansal, Aditya

AU - Pandey, Mukesh

AU - Peng, Kah-Whye

AU - Suksanpaisan, Lukkana

AU - Russell, Stephen J

AU - DeGrado, Timothy R

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N2 - The sodium/iodide symporter (NIS) is under investigation as a reporter for noninvasive imaging of gene expression. Although 18F-Tetrafluoroborate (18F-TFB, 18F-BF4-) has shown promise as a PET imaging probe for NIS, the current synthesis method using isotopic exchange gives suboptimal radiochemical yield and specific activity. The aim of this study was to synthesize 18F-TFB via direct radiofluorination on boron trifluoride (BF3) to enhance both labeling yield and specific activity and evaluation of specific activity influence on tumor uptake. Methods: An automated synthesis of 18F-TFB was developed whereby cyclotron-produced 18F-fluoride was trapped on a quaternary methyl ammonium anion exchange cartridge, then allowed to react with BF3 freshly preformulated in petroleum ether/tetrahydrofuran (50:1). The resultant 18F-TFB product was retained on the quaternary methyl ammonium anion exchange cartridge. After the cartridge was rinsed with tetrahydrofuran and water, 18F-TFB was eluted from the cartridge with isotonic saline, passing through 3 neutral alumina cartridges and a sterilizing filter. Preclinical imaging studies with 18F-TFB were performed in athymic mice bearing NIS-expressing C6-glioma subcutaneous xenografted tumors to determine the influence of specific activity on tumor uptake. Results: Under optimized conditions, 18F-TFB was synthesized in a radiochemical yield of 20.0% ± 0.7% (n 5 3, uncorrected for decay) and greater than 98% radiochemical purity in a synthesis time of 10 min. Specific activities of 8.84 ± 0.56 GBq/μmol (n 5 3) were achieved from starting 18F-fluoride radioactivities of 40-44 GBq. An avid uptake of 18F-TFB was observed in human NIS (hNIS)-expressing C6-glioma xenografts as well as expected NIS-mediated uptake in the thyroid and stomach. There was a positive correlation between the uptake of 18F-TFB in hNISexpressing tumor and specific activity. Conclusion: A rapid, practical, and high-specific-Activity synthesis of the NIS reporter probe 18F-TFB was achieved via direct radiofluorination on BF3 using an automated synthesis system. The synthesis of high-specific-Activity 18F-TFB should enable future clinical studies with hNIS gene reporter viral constructs.

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