Comparison of the tumor and inflammation uptake of [¹⁸F]-deoxy-1-fluoro-scyllo-inositol and [¹⁸F]-FDG in athymic mice bearing human breast cancer xenografts

Objectives Our preliminary work demonstrated that [¹⁸F]1-deoxy-1-fluoro-scyllo-inositol ([¹⁸F]-SI) may be a promising PET imaging agent for breast cancer (BC) (Chem. Commun., 2009, 5527). The objectives of the present work were to automate the radiosynthesis of [¹⁸F]-SI and to compare the uptake of [¹⁸F]-SI and [¹⁸F]-FDG in human BC xenografts and inflammation in athymic mice.

Methods Radiosynthesis of [¹⁸F]-SI was automated, as per our previously described 3-step reaction, using a commercial synthesis module. Subcutaneous MDA-MB-231 human BC xenografts and turpentine-induced s.c. inflammation were established in female CD1 athymic mice. Mice (n=5 per group) were intravenously injected with [¹⁸F]-SI or [¹⁸F]-FDG (7.5 ± 0.6 MBq) and immediately anesthetized using 2% isoflurane in oxygen. PET-CT imaging and ex vivo biodistribution studies were performed at 60 minutes post-injection.

Results [¹⁸F]-SI was prepared with good radiochemical yields (23.8 ± 0.6%; uncorrected), high specific activity (>10 Ci/μmol at EOS; determined by LC-MS-MS) and high radiochemical purity (>99%) within 65 minutes. The tumor uptake of [¹⁸F]-SI was comparable to that of [¹⁸F]-FDG (4.6 ± 0.5 %ID/g vs. 5.5 ± 2.1 %ID/g, P=0.40. Uptake of [¹⁸F]-SI in inflammatory tissue was moderately lower than that of [¹⁸F]-FDG (3.5 ± 0.5 %ID/g vs. 5.5 ± 1.0 %ID/g, P=0.004). All tumors and inflammation were visualized by PET imaging and there was a reasonable correlation between the biodistribution and ROI analyses (r=0.70). Consistent with our preliminary results, brain uptake of [¹⁸F]-SI was negligible compared to that of [¹⁸F]-FDG (0.5 ± 0.1 %ID/g vs. 8.1 ± 1.0 %ID/g, P<0.0001).

Conclusions Radiosynthesis of [¹⁸F]-SI was successfully automated for routine production. Uptake of [¹⁸F]-SI in tumors and inflammation was comparable to that of [¹⁸F]-FDG. Future studies evaluating [¹⁸F]-SI for visualizing different BC xenograft phenotypes are underway.

Research Support OICR, NSERC and CIH