Re: Increased 18F-2-Fluorodeoxysorbitol (18F-FDS) Activity in a Pituitary Spindle Cell Carcinoma

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To the Editor:
We read the report by Cheng et al1 describing 18F-FDG and 18F-2-fluorodeoxysorbitol (18F-FDS) PET to differentiate malignancy from inflammation in a 33-year-old woman with a pituitary spindle cell carcinoma. Li et al2 were the first to synthesize 18F-FDS and reported visualization of both glioblastoma xenografts (U87MG) and inflammatory foci in mice, at early time points after tracer injection. It appears that the strong implication by Cheng et al1 that 18F-FDS has the potential to differentiate malignancy from inflammation is admirable in enthusiasm but may be factually inconsistent with the current state of the art.
Cheng et al1 reported PET SUVmax of 4.73 (18F-FDG) and 1.49 (18F-FDS) at the site of the pituitary spindle cell carcinoma. However, Li et al2 reported that 18F-FDS exhibits very poor in vitro uptake by mammalian cells—0.1% for 18F-FDS versus up to 40% for 18F-FDG in U87MG cells. There are no transporters for 18F-FDS entry into mammalian cells and the substitution of the hydroxyl group by fluorine at the 2C-position completely abrogates the recognition by mammalian enzymes.3 Moreover, Li et al2 visualized tumors and inflammation in mice by 18F-FDS PET in the context of high background at earlier time points after tracer injection (5–60 minutes). Therefore, given the lack of specific-uptake mechanisms, they suggested that increased blood flow and leaky vasculature were responsible for visualization of xenografts (U87MG), as well as inflammatory foci.2 These findings are also consistent with the data by Weinstein et al,4 who also demonstrated the lack of 18F-FDS uptake in healthy mammalian or cancer cells. Interestingly, Weinstein et al4 reported substantial (~1000-fold higher than mammalian cells) and specific uptake of 18F-FDS in gram-negative bacteria (Enterobacteriaceae). At 120 minutes after 18F-FDS injection in mice, infectious foci due to these bacteria were clearly visualized by PET, but no appreciable signal was noted at the sites of (sterile) inflammation or U87MG brain xenografts.4 Furthermore, dynamic 18F-FDS PET studies in mice with U87MG brain tumors demonstrated some initial signal, which, however, dissipated 60 to 120 minutes after tracer injection.
In conclusion, 18F-FDS may be useful to detect infectious foci due to Enterobacteriaceae.4 While the sensitivity and specificity of this technique in the clinical setting remain to be determined, it is likely that 18F-FDS uptake at the sites of sterile inflammation and malignancy (as demonstrated by Cheng et al) is consistent with a nonspecific blood pool effect, that is, capillary leak at the site of inflammation or malignancy.
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