A Prospective Study Comparing ^99mTc-Hydroxyethylene-Diphosphonate Planar Bone Scintigraphy and Whole-Body SPECT/CT with ¹⁸F-Fluoride PET/CT and ¹⁸F-Fluoride PET/MRI for Diagnosing Bone Metastases

Abstract

See an invited perspective on this article on page 1776.We prospectively evaluated and compared the diagnostic performance of 99m Tc-hydroxyethylene-diphosphonate ( 99m Tc-HDP) planar bone scintigraphy (pBS), 99m Tc-HDP SPECT/CT, 18 F-NaF PET/CT, and 18 F-NaF PET/MRI for the detection of bone metastases. Methods: One hundred seventeen patients with histologically proven malignancy referred for clinical pBS were prospectively enrolled. pBS and whole-body SPECT/CT were performed followed by 18 F-NaF PET/CT within 9 d. 18 F-NaF PET/MRI was also performed in 46 patients. Results: Bone metastases were confirmed in 16 patients and excluded in 101, which was lower than expected. The number of equivocal scans was significantly higher for pBS than for SPECT/CT and PET/CT (18 vs. 5 and 6, respectively; P 5 0.004 and 0.01, respectively). When equivocal readings were excluded, no statistically significant difference in sensitivity, specificity, positive predictive value, negative predictive value, or overall accuracy were found when comparing the different imaging techniques. In the per-patient analysis, equivocal scans were either assumed positive for metastases ("pessimistic analysis") or assumed negative for metastases ("optimistic analysis"). The percentages of misdiagnosed patients for the pessimistic analysis were 21%, 15%, 9%, and 7% for pBS, SPECT/CT, PET/CT, and PET/MRI, respectively. Corresponding figures for the optimistic analysis were 9%, 12%, 5%, and 7%. In those patients identified as having bone metastases according to the reference standard, SPECT/CT, 18 F-NaF PET/CT, and PET/MRI detected additional lesions compared with pBS in 31%, 63%, and 71%, respectively. Conclusion: 18 F-NaF PET/CT and whole-body SPECT/CT resulted in a significant reduction of equivocal readings compared with pBS, which implies an improved diagnostic confidence. However, the clinical benefit of using, for example, 18 F-NaF PET/CT or PET/MRI as compared with SPECT/CT and pBS in this patient population with a relatively low prevalence of bone metastases (14%) is likely limited. This conclusion is influenced by the low prevalence of patients with osseous metastases. There may well be significant differences in the sensitivity of SPECT/CT, PET/CT, and PET/MRI compared with pBS, but a larger patient population or a patient population with a higher prevalence of bone metastases would have to be studied to demonstrate this.

Added value of 68Ga-PSMA PET/CT for the detection of bone metastases in patients with newly diagnosed prostate cancer and a previous 99mTc bone scintigraphy

“…However, performing biopsy routinely is not ethically reasonable, and consequently, a composite endpoint (BVC) was applied in the present study. A BVC has previously been used in diagnostic studies of bone metastases, including studies comparing 68 Ga-PSMA-11 PET/CT to BS [6][7][8]15]. One of the limitations of the BVC is that the index test itself often plays a key role in the definition of the BVC, as the interpretation of a new and promising method might be unreasonably trusted in the final conclusion based on the BVC.…”

“…In most cases, a histopathologic reference standard was not available for ethical and practical reasons. For the present study, we defined a "best valuable comparator" (BVC) for the presence or absence of bone metastases at the patient level similar to previous diagnostic studies of bone metastases [6,8,15]. The BVC was based on all available imaging results available at the time of staging as well as supplementary and/or follow-up imaging (all modalities).…”

Use of modern imaging methods to facilitate trials of metastasis-directed therapy for oligometastatic disease in prostate cancer: a consensus recommendation from the EORTC Imaging Group

“…Table A1) 18 F--natriumfluoride ( 18 F--NaF) PET, like 99mTc--MDP largely reflects regional bone blood flow and osteoblastic activity so that its specificity and sensitivity for lytic metastases and soft tissue disease is limited 27 . 18 F--NaF PET/CT does not offer a substantial clinical benefit compared to BS (including SPECT/CT) 27 .…”

“…PET with 18 F--or 11 C radiolabeled choline images cell membrane phospholipid synthesis and accordingly cell growth. 18 F--labelling is more widely available and more convenient because of its longer half--life (110 versus 20 minutes) and better spatial resolution (shorter positron range of 7 18 F) 27 . 18 F--choline PET/CT is mainly used for restaging patients at BCR ( Figure A1).…”

David Versus the Goliaths for the Detection of Bone Metastases

“…This is what makes the report by Löfgren et al (12) remarkable. Löfgren et al expertly perform a prospective trial comparing the ability of David versus the Goliaths to detect bone metastases in a cohort of patients with known malignancy and clinical suspicion for bone metastases, and find no difference between them.…”