Quantitative SPECT/CT SUVmax: Improving Diagnostic Confidence in Differentiating Metastatic from Degenerative Bone Lesions in Breast Cancer

Breast cancer bone metastases are predominantly osteolytic. Tumor-derived parathyroid hormone-related peptide increases receptor activator of nuclear factor-kappa B ligand (RANKL) expression in osteoblasts. RANKL binds receptor activator of nuclear factor-kappa B (RANK) on osteoclast precursors, promoting osteoclast activation and bone resorption. The resulting release of matrix-embedded growth factors, including transforming growth factor-beta and insulin-like growth factors, contributes to tumor progression and a reparative osteoblastic response detectable with technetium-99m methylene diphosphonate (99ᵐTc-MDP). This study evaluated the diagnostic performance of body-weight-normalized maximum standardized uptake value (SUVmax,bw) from quantitative single-photon emission computed tomography (SPECT)/computed tomography (CT) for differentiating metastatic from degenerative bone lesions in patients with breast cancer. This retrospective, single-center diagnostic-accuracy study included patients with confirmed breast cancer who underwent planar bone scintigraphy and regional quantitative SPECT/CT at a tertiary referral hospital between May 2024 and June 2025. One to five lesions per patient were evaluated. Lesions were classified using a composite reference standard incorporating radiotracer uptake pattern and distribution, CT morphology, clinical information, and serial imaging or treatment response when available. SUVmax,bw was measured from semiautomatically delineated volumes of interest on fused SPECT/CT images. SUVmax,bw values were compared using the Mann–Whitney U test. Receiver operating characteristic analysis and the Youden index were used to determine the area under the curve (AUC), optimal threshold, and diagnostic performance. Because some patients contributed multiple lesions, the reported estimates were based on an unadjusted lesion-level analysis and were interpreted as exploratory. Sixty-two patients contributed 182 lesions, including 134 metastatic and 48 degenerative lesions. SUVmax,bw was higher in metastatic than degenerative lesions (28.60 ± 11.40 vs. 10.10 ± 3.65 g/mL; p < 0.001). The lesion-level AUC was 0.964. At a threshold of 16.7 g/mL, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 92.54, 97.92, 99.20, 82.46, and 93.96%, respectively. Quantitative 99ᵐTc-MDP SPECT/CT SUVmax,bw may serve as a useful objective parameter for differentiating metastatic from degenerative bone lesions. Its integration with CT morphology and clinical information may improve lesion characterization, although the present lesion-level findings require confirmation using patient-clustered statistical analysis.