Off-Target Report on ¹⁸F-Sodium Fluoride PET/CT for Detection of Skeletal Metastases in Prostate Cancer

TO THE EDITOR: In a recent report in the Journal of Nuclear Medicine, cited by AuntMinnie, Zacho et al. found, according to the title of their communication, “No added value of ¹⁸F-sodium fluoride (¹⁸F-NaF) PET/CT for the detection of bone metastases in patients with newly diagnosed prostate cancer with normal bone scintigraphy” (1). In 81 intermediate- or high-risk prostate cancer patients with negative bone scintigraphy scheduled for prostatectomy, ¹⁸F-NaF PET/CT “indicated bone metastasis” in 1 and was equivocal in 7 patients. None of these patients exhibited biochemical failure (prostate-specific antigen level ≥ 2 ng/mL 6 wk/6 mo after radical prostatectomy), whereas all 6 patients with biochemical failure had negative ¹⁸F-NaF PET/CT (and negative bone scintigraphy)—findings making the authors conclude as stated in their title.

Their report is off-target because (1) skeletal metastases are bone marrow and not bone metastases and (2) neither ¹⁸F-NaF PET/CT nor bone scintigraphy mirror bone marrow metastases, but late-occurring bone changes that may or may not be due to active cancerous processes (2,3). As in other recent communications (4,5), the authors disregarded the true nature of skeletal metastases, which home and grow in the bone marrow long before they give rise to structural changes in the osseous bone substance that can be detected by bone scintigraphy, ¹⁸F-NaF PET/CT, or other imaging modalities. This was highlighted more than 10 y ago by Basu et al. (6,7) and has recently given rise to comments in both the Journal of Nuclear Medicine and the European Journal of Nuclear Medicine and Molecular Imaging (2,3), the latter calling for a much needed paradigm shift, since we cannot go on using methods unable to fulfil their stated purpose and that, therefore unfortunately, may lead to inappropriate patient management.

The reason why Zacho et al. did not observe an association between biochemical failure and abnormal ¹⁸F-NaF PET/CT findings is a simple one: there should not be an association—at least not a very close one. An increase in prostate-specific antigen, however unspecific, is usually a reaction to cancer cells that are still present and growing after prostatectomy. However, this may have little to do with what is seen by ¹⁸F-NaF PET/CT or bone scintigraphy, since both methods depict unspecific structural changes in osseous tissue that occur late in the development of skeletal metastasis and remain unchanged for a long time after the cancer may have disappeared, for instance, due to effective chemo- or radiation therapy (2,3). Thus, it is time to realize that all imaging modalities demonstrating structural bone changes are not reliable harbingers of skeletal metastases and should be abandoned in favor of ¹⁸F-FDG PET/CT and, when it comes to prostate cancer, perhaps PSMA PET/CT. Time will show which of the latter 2 approaches are preferable for showing bone marrow metastases in prostate cancer. However, in most other cancers, ¹⁸F-FDG PET/CT will probably prevail for this purpose for reasons stated in detail elsewhere (2,3). Experts in nuclear medicine and molecular imaging should understand and communicate this, because otherwise how do we make cooperating surgeons and oncologists understand and act accordingly?

• © 2019 by the Society of Nuclear Medicine and Molecular Imaging.