Digital versus analogue PET in parathyroid imaging: comparison of PET metrics and machine learning-based characterisation of hyperfunctioning lesions (the DIGI-PET study)

Purpose: To compare PET-derived metrics between digital and analogue PET/CT in hyperparathyroidism, and to assess whether machine learning (ML) applied to quantitative PET parameters can distinguish parathyroid adenoma (PA) from hyperplasia (PH). Methods: From an initial multi-centre cohort of 179 patients, 86 were included, comprising 89 PET-positive lesions confirmed histologically (74 PA, 15 PH). Quantitative PET parameters—maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV), target-to-background ratio (TBR), and maximum diameter—along with serum PTH and calcium levels, were compared between digital and analogue PET scanners using the Mann–Whitney U test. Receiver operating characteristic (ROC) analysis identified optimal threshold values. ML models (LASSO, decision tree, Gaussian naïve Bayes) were trained on harmonised quantitative features to distinguish PA from PH. Results: Digital PET detected significantly smaller lesions than analogue PET, in both metabolic volume (1.32 ± 1.39 vs. 2.36 ± 2.01 cc; p < 0.001) and maximum diameter (8.35 ± 4.32 vs. 11.87 ± 5.29 mm; p < 0.001). PA lesions showed significantly higher SUVmax and TBR compared to PH (SUVmax: 8.58 ± 3.70 vs. 5.27 ± 2.34; TBR: 14.67 ± 6.99 vs. 8.82 ± 5.90; both p < 0.001). The optimal thresholds for identifying PA were SUVmax > 5.89 and TBR > 11.5. The best ML model (LASSO) achieved an AUC of 0.811, with 79.7% accuracy and balanced sensitivity and specificity. Conclusions: Digital PET outperforms analogue system in detecting small parathyroid lesions. Additionally, ML analysis of PET-derived metrics and PTH may support non-invasive distinction between adenoma and hyperplasia.