MO-AB-BRA-05: [18F]NaF PET/CT Imaging Biomarkers in Metastatic Prostate Cancer

Purpose: Clinical use of ¹⁸F-Sodium Fluoride (NaF) PET/CT in metastatic settings often lacks technology to quantitatively measure full disease dynamics due to high tumor burden. This study assesses radiomics-based extraction of NaF PET/CT measures, including global metrics of overall burden and local metrics of disease heterogeneity, in metastatic prostate cancer for correlation to clinical outcomes. Methods: Fifty-six metastatic Castrate-Resistant Prostate Cancer (mCRPC) patients had NaF PET/CT scans performed at baseline and three cycles into chemotherapy (N=16) or androgen-receptor (AR) inhibitors (N=39). A novel technology, Quantitative Total Bone Imaging (QTBI), was used for analysis. Employing hybrid PET/CT segmentation and articulated skeletal-registration, QTBI allows for response assessment of individual lesions. Various SUV metrics were extracted from each lesion (iSUV). Global metrics were extracted from composite lesion-level statistics for each patient (pSUV). Proportion of detected lesions and those with significant response (%-increase or %-decrease) was calculated for each patient based on test-retest limits for iSUV metrics. Cox proportional hazard regression analyses were conducted between imaging metrics and progression-free survival (PFS). Results: Functional burden (pSUV_total) assessed mid-treatment was the strongest univariate predictor of PFS (HR=2.03; p<0.0001). Various global metrics outperformed baseline clinical markers, including fraction of skeletal burden, mean uptake (pSUV_mean), and heterogeneity of average lesion uptake (pSUV_hetero). Of 43 patients with paired baseline/mid-treatment imaging, 40 showed heterogeneity in lesion-level response, containing populations of lesions with both increasing/decreasing metrics. Proportion of lesions with significantly increasing iSUV_mean was highly predictive of clinical PFS (HR=2.0; p=0.0002). Patients exhibiting higher proportion of lesions with decreasing iSUV_total saw prolonged radiographic PFS (HR=0.51; p=0.02). Conclusion: Technology presented here provides comprehensive disease quantification on NaF PET/CT imaging, showing strong correlation to clinical outcomes. Total functional burden as well as proportions of similarly responding lesions was predictive of PFS. This supports ongoing development of NaF PET/CT based imaging biomarkers in mCRPC. Prostate Cancer Foundation