Results of a phase 3 trial support the use of 18F-sodium fluoride (18F-NaF) over 99mTc-methylene diphosphonate (99mTc-MDP) for the detection of bone metastasis. 

PET-CT with 18F-NaF proved more accurate than single-photon emission CT (SPECT) with 99mTc-MDP for detecting bone metastasis in patients with high-risk prostate or breast cancer. These results were published in The Lancet Oncology.

The trial (MITNEC-A1; Identifier: NCT01930812) included 261 evaluable patients with high-risk prostate cancer (n=204) or breast cancer (n=57) who required bone scintigraphy for the detection of metastasis.

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The median age was 68.8 years in the prostate cancer group and 58.5 years in the breast cancer group. All prostate cancer patients and 4% of breast cancer patients were men. A majority in both groups (79% and 81%, respectively) were White. 

Prior treatments (in the prostate and breast cancer groups, respectively) included primary surgery (42% and 79%), radiotherapy (26% and 56%), chemotherapy (4% and 65%), androgen deprivation therapy (61% and 0%), and hormone therapy (0% and 54%).

Each patient underwent 18F-NaF PET-CT and 99mTc-MDP SPECT within 14 days of each other. The overall accuracy of the 2 imaging modalities — based on independent reviews from 2 experts for each modality — was compared with histopathologic, clinical, and imaging outcomes observed during a 24-month follow-up (reference standard).

According to the reference standard, 42% of patients had bone metastases. Metastases were more likely in patients with prostate cancer (44%) than in those with breast cancer (33%).

Sensitivity was significantly higher with 18F-NaF PET-CT than with 99mTc-MDP SPECT (78.9% and 63.3%, respectively; P =.0007). The same was true for negative predictive value (85.4% and 76.9%, respectively; P =.0006) and accuracy (84.3% and 77.4%, respectively; P =.016). 

However, 18F-NaF PET-CT and 99mTc-MDP SPECT had similar specificity (88.2% and 87.5%, respectively; P =.86) and positive predictive value (82.7% and 78.4%, respectively; P =.038).

There were 65 patients who had metastatic bone lesions on both scans. In this group, the 18F-NaF PET-CT scans detected significantly more lesions than the 99mTc-MDP SPECT scans (P <.0001).

During 18F-NaF PET-CT , patients’ blood pressure and heart rate were observed to decrease between baseline and 60 minutes after 18F-NaF injection, but these changes were not considered clinically relevant. No grade 1 or higher adverse events occurred during 18F-NaF PET-CT.

“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 researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


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. Published online November 4, 2022. doi:10.1016/S1470-2045(22)00642-8