Differentiation of metastatic vs degenerative joint disease using semi-quantitative analysis with (18)F-NaF PET/CT in castrate resistant prostate cancer patients

Abstract

Fluorine 18 Sodium Fluoride ((18)F-NaF) (sodium fluoride) PET/CT is a highly sensitive but is a non-specific method for identifying bone metastases. Qualitative scan interpretation using low dose CT for lesion localization is often complicated by the presence of co-existing degenerative joint disease (DJD). A semi-quantitative analysis might help in accurately differentiating benign from metastatic osseous lesions. The aim of the study was to evaluate the clinical utility of (18)F-NaF PET/CT in differentiating DJD from metastatic disease in the skeleton using a qualitative analysis as well as a semi-quantitative approach using the SUVmax and to determine if there is an upper limit of SUVmax value that can reliably differentiate metastases from DJD. Baseline (18)F-NaF PET/CT scans were performed for 17 castrate resistant prostate cancer patients (CRPC). A qualitative as well as semi-quantitative analysis using maximum standardized uptake value (SUVmax) based on body weight was performed for 65 metastatic and 56 DJD sites identified on the low dose CT scan acquired as a part of whole body PET/CT scan. The SUVmax range in DJD was 2.6-49.9 (mean: 6.2). The SUVmax range for metastatic lesions was 11.2-188 (mean: 160). The SUVmax value for metastatic as well as areas of DJD showed significant variation during treatment. Bone metastases showed statistically significantly higher SUVmax than DJD using a mixed effect regression model. ROC/AUC analysis was performed based on averaging the SUVs over all lesions in each subject. The AUC was found to be fairly high at 0.964 (95% CI: 0.75-0.996). The SUVmax over 50 always represented a bone metastasis and below 12 always represented a site of DJD. The results of our preliminary data show that semi-quantitative analysis is complementary to the qualitative analysis in accurately identifying DJD from metastatic disease. The cut-off SUVmax of 50 can help in differentiating DJD from bone metastases.

Keywords: F-18 NaF; PET/CT; bone metastases; castrate resistant prostate cancer; degenerative joint disease.

Figure 1

This figure shows the box plots for all the representative degenerative joint disease (DJD) and metastases lesions. The distributions were compared using a 2-sided t-test (p < 0.001).

Figure 2

Box plots of the average SUVmax values of the representative degenerative joint disease (DJD) and metastases (Bone Mets) lesions of each patient. The distributions were compared using a 2-sided t-test (p < 0.001)..

Figure 3

Histograms of the average SUVmax values of the representative degenerative joint disease (DJD) and bone metastases (Bone Mets) lesions of each patient, showing the overlap of the two distributions.

Figure 4

ROC curve coming from using different thresholds of patient averaged SUVmax to discriminate between degenerative and metastatic bone lesions; Area under the curve (AUC) = 0.976 (0.804-0.997).

Figure 5

72 year old male with CRPC(Castrate resistant prostate cancer). ¹⁸F-NaF PET/CT images of upper thoracic spine. CT (left), PET (middle) and fused PET/CT images (right) in axial, coronal and sagittal views. Prominent increased uptake is seen in the spinous process metastatic lesion on PET images (thick black arrow); CT images show a sclerotic lesion in the spinous process. (Thick white arrow). Increased uptake (thin black arrow) is also seen in a thoracic vertebra which corresponds to an osteophyte on CT images (thin white arrow). The intensity of uptake in the osteophyte is much less compared to the uptake seen in the spinous process.