Real-world use of [18 F]fluorocholine PET/CT as a second-level imaging modality in primary hyperparathyroidism: a two-center observational study

Background [18 F]fluorocholine PET/CT is increasingly used for localization of hyperfunctioning parathyroid tissue, but its real-world positioning after non-conclusive conventional imaging remains less clearly defined. This retrospective, observational, two-center study evaluated the use of [18 F]fluorocholine PET/CT as a second-level imaging modality in consecutive patients with suspected or biochemically confirmed primary hyperparathyroidism, within the Italian national reimbursement framework under Law 648/96. Results A total of 599 consecutive patients evaluated between February 2022 and July 2025 were included. [99 m]Tc-sestamibi imaging, with or without SPECT/CT, was positive/localizing in 270/599 patients (45.1%) and negative or doubtful/non-conclusive in 329/599 patients (54.9%). Overall, 132/599 patients (22.0%) underwent [18 F]fluorocholine PET/CT, all within the subgroup with negative or doubtful/non-conclusive sestamibi imaging, corresponding to 132/329 patients (40.1%). PET/CT was positive in 100/132 patients (75.8%) and negative in 32/132 patients (24.2%). Baseline PTH was significantly higher in PET-positive than in PET-negative patients: 118.8 (IQR 94.0–156.5) versus 105.0 (IQR 81.8–120.5), p = 0.012. Surgery was performed in 154/599 patients (25.7%) overall and was more frequent in PET-positive than in PET-negative patients: 41/100 (41.0%) versus 3/32 (9.4%), p < 0.001; OR 6.72, 95% CI 1.92–23.53. In exploratory multivariable analysis, PET/CT positivity remained independently associated with surgical management after adjustment for baseline PTH, serum calcium, age, and sex: adjusted OR 5.89, 95% CI 1.60–21.63, p = 0.008. Among patients with paired postoperative data, significant reductions were observed in PTH and serum calcium. Exploratory ROC analyses showed only modest discriminative ability of baseline PTH for imaging positivity. Conclusions In this large two-center real-world cohort, [18 F]fluorocholine PET/CT was selectively used as a second-level imaging modality in patients with primary hyperparathyroidism and negative or doubtful/non-conclusive [99 m]Tc-sestamibi imaging. PET-positive findings were associated with higher baseline PTH levels and subsequent surgical management, supporting the role of [18 F]fluorocholine PET/CT as a decision-supporting modality within the diagnostic pathway.