Synthesis and evaluation of 18F-hexafluorophosphate as a novel PET probe for imaging of sodium/iodide symporter in a murine C6-glioma tumor model. Issue 1 (1st January 2018)

• Record Type: Journal Article
• Authors: Jiang, Huailei; Bansal, Aditya; Goyal, Ribu; Peng, Kah-Whye; Russell, Stephen J.; DeGrado, Timothy R.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 1(2018)
• Page Start: 225
• Page End: 231
• Publication Date: 2018-01-01
• Subjects: Sodium/iodide symporter -- Hexafluorophosphate -- Fluorine-18 -- PET imaging -- Radiofluorination; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.11.034
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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 18 F-labeled hexafluorophosphate (HFP or PF6 − ) as a high-affinity iodide analog for NIS imaging. 18 F-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. 18 F-HFP was obtained in radiochemical yield of 10 ± 5%, radiochemical purity of >96% and specific radioactivity of 604 ± 18 MBq/µmol. Specific uptake of 18 F-HFP and high affinity of 19 F-HFP were observed in hNIS+ C6-glioma cells. PET imaging showed robust uptake of 18 F-HFP in NIS-expressing tissues (thyroid, stomach, and hNIS+ C6 glioma xenografts), and the uptake of 18 F-HFP was blocked by NaClO4 pretreatment. Specific accumulation in hNIS-expressing xenograft (hNIS+) was observed relative to isogenic control tumor (hNIS−). Clearance of 18 F-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 18 F-HFP. Although improvement in specific radioactivity is desirable, the results indicate that 18 F-HFP is a promising candidate radiotracer for further evaluation for NIS imaging.