Synthesis and evaluation of 18F-hexafluorophosphate as a novel PET probe for imaging of sodium/iodide symporter in a murine C6-glioma tumor model

Huailei Jiang, Aditya Bansal, Ribu Goyal, Kah-Whye Peng, Stephen J Russell, Timothy R DeGrado

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Noninvasive imaging of iodide uptake via the sodium/iodide symporter (NIS) has received great interest for evaluation of thyroid cancer and reporter imaging of NIS-expressing viral therapies. In this study, we investigate 18F-labeled hexafluorophosphate (HFP or PF6) as a high-affinity iodide analog for NIS imaging. 18F-HFP was synthesized by radiofluorination of phosphorus pentafluoride·N-methylpyrrolidine complex and evaluated in human NIS (hNIS)-expressing C6 glioma cells and a C6 glioma xenograft mouse model. 18F-HFP was obtained in radiochemical yield of 10 ± 5%, radiochemical purity of >96% and specific radioactivity of 604 ± 18 MBq/µmol. Specific uptake of 18F-HFP and high affinity of 19F-HFP were observed in hNIS+ C6-glioma cells. PET imaging showed robust uptake of 18F-HFP in NIS-expressing tissues (thyroid, stomach, and hNIS+ C6 glioma xenografts), and the uptake of 18F-HFP was blocked by NaClO4 pretreatment. Specific accumulation in hNIS-expressing xenograft (hNIS+) was observed relative to isogenic control tumor (hNIS−). Clearance of 18F-HFP was predominantly through renal excretion. The biodistribution showed consistent results with PET imaging. Minimal bone uptake was observed over 2 h period post-injection, indicating excellent in vivo stability of 18F-HFP. Although improvement in specific radioactivity is desirable, the results indicate that 18F-HFP is a promising candidate radiotracer for further evaluation for NIS imaging.

Original languageEnglish (US)
Pages (from-to)225-231
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2018

Keywords

  • Fluorine-18
  • Hexafluorophosphate
  • PET imaging
  • Radiofluorination
  • Sodium/iodide symporter

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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