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

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.

• Authors: Huailei Jiang, Aditya Bansal, Ribu Goyal, Kah-Whye Peng, Stephen J Russell, Timothy R DeGrado
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 26 Issue 1 Pg. 225-231 (01 01 2018) ISSN: 1464-3391 [Electronic] England
• PMID: 29198608 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Fluorine Radioisotopes
• Radiopharmaceuticals
• Symporters
• sodium-iodide symporter

Topics

• Animals
• Dose-Response Relationship, Drug
• Female
• Fluorine Radioisotopes
• Glioma (diagnostic imaging, metabolism)
• Humans
• Mice
• Mice, Nude
• Molecular Imaging
• Molecular Structure
• Neoplasms, Experimental (diagnostic imaging, metabolism)
• Positron-Emission Tomography
• Radiopharmaceuticals (chemical synthesis, chemistry, pharmacokinetics)
• Structure-Activity Relationship
• Symporters (analysis, metabolism)