18F-Sodium Fluoride PET-CT Detects Bone Metastases More Accurately in 2 Cancers


18F-sodium fluoride PET-CT appeared to be a more accurate identifier of bone metastases in patients with breast and prostate cancer than the standard SPECT method.

Bone metastases were more accurately detected with the use of 18F-sodium fluoride (18F-NaF) PET-CT imaging in patients with high-risk breast and prostate cancer than 99mTc-methylene diphosphonate (99mTc-MDP) single-photon emission CT (SPECT) imaging, according to findings from the phase 3 MITNEC-A1 trial (NCT01930812).

18F-NaF PET-CT imaging detected osseous metastases with an accuracy of 84.3% (95% CI, 79.9%-88.7%) compared with 77.4%(95% CI, 72.3%-82.5%) for 99mTc-MDP SPECT imaging, translating to an overall difference of 6.9% (95% CI, 1.3-12.5; P = .016). 18F-NaF PET-CT also demonstrated higher sensitivity and negative predictive value vs 99mTc-MDP with no significant difference in specificity or positive predictive value. Moreover, no dose reductions were necessary in either group, as there were no reports of adverse effects (AEs) of grade 1 or higher.

“Accurate detection of osseous metastases is important for staging, treatment planning, monitoring response to therapy, and detection of areas at risk for skeletal-related adverse events in patients with a wide range of malignancies,” the investigators wrote. “99mTc-MDP SPECT has been considered as the method of choice for the evaluation of bone metastases in various cancers. Since the limited spatial resolution of planar scintigraphy and SPECT affects the sensitivity of bone scintigraphy for the detection of bone metastases, transition to the higher resolution of PET-CT with the use of 18F-NaF for the detection of these metastases is appealing.”

Investigators enrolled 288 patients from July 11, 2014, to March 3, 2017. An evaluable imaging core population that included 204 patients with prostate cancer and 57 with breast cancer was extracted from this enrolled cohort. Median ages were 68.8 (95% CI, 63.0-74.4) and 58.5 years (95% CI, 49.7-66.8) in the prostate and breast cancer groups, respectively. All patients in the prostate cancer group were men and 96% of those in the breast cancer group were women. The vast majority of patients in both groups were White (79% vs 81%, respectively).

In the overall group, 42% (n = 109) of patients experienced bone metastases, including 44% (n = 90) of those with prostate cancer and 33% (n = 19) of those with breast cancer. The median follow-up was 735 days (interquartile range [IQR], 727-750).

According to a post-hoc subset analysis, 18F-sodium fluoride PET-CT performed better than the 99mTc-MDP SPECT in terms of accuracy, sensitivity, and negative predictive value in the prostate cancer group, but both methods had equivalent specificity and positive predictive value. Meanwhile, in the breast cancer group, 18F-sodium fluoride PET-CT demonstrated better accuracy, specificity, and positive predictive value, but had the same sensitivity and negative predictive value as its counterpart.

18F-NaF PET-CT also detected significantly more metastatic bone lesions than 99mTc-MDP SPECT in the 65 patients whose metastases were detected on both scans (P <.0001).

In terms of physiological effects, 18F-NaF PET-CT led to vital sign fluctuation between the pre-injection timepoint and 60 minutes after the 18F-NaF injection, but the changes were not deemed clinically significant.

“Considering all the advantages and the ability to detect bone metastasis with higher sensitivity and accuracy, 18F-NaF has the potential to displace 99mTc-MDP as the bone imaging radiopharmaceutical of choice,” the investigators concluded.


Bénard F, Harsini S, Wilson D, et al. Intra-individual comparison of 18F-sodium fluoride PET-CT and 99mTc bone scintigraphy with SPECT in patients with prostate cancer or breast cancer at high risk for skeletal metastases (MITNEC-A1): a multicentre, phase 3 trial. Lancet Oncol. 2022;23(12):1499-1507. doi:10.1016/S1470-2045(22)00642-8

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