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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Synthesis and evaluation of 18 F-hexafluorophosphate as a novel PET probe for imaging of sodium/iodide symporter in a murine C6-glioma tumor model.
Bioorganic & Medicinal Chemistry 2018 January 2
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 investigate18 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 of18 F-HFP and high affinity of19 F-HFP were observed in hNIS+ C6-glioma cells. PET imaging showed robust uptake of18 F-HFP in NIS-expressing tissues (thyroid, stomach, and hNIS+ C6 glioma xenografts), and the uptake of18 F-HFP was blocked by NaClO4 pretreatment. Specific accumulation in hNIS-expressing xenograft (hNIS+) was observed relative to isogenic control tumor (hNIS-). Clearance of18 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 of18 F-HFP. Although improvement in specific radioactivity is desirable, the results indicate that18 F-HFP is a promising candidate radiotracer for further evaluation for NIS imaging.
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