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PurposeThe great spatial and temporal resolution of positron emission tomography might provide the answer for patients with primary hyperparathyroidism (pHPT) and non-localized parathyroid glands. We performed a systematic review of the evidence regarding all investigated tracers.MethodsA study was considered eligible when the following criteria were met: (1) adults ≥17years old with non-familial pHPT, (2) evaluation of at least one PET isotope, and (3) post-surgical and pathological diagnosis as the gold standard. Performance was expressed in sensitivity and PPV.ResultsTwenty-four papers were included subdivided by radiopharmaceutical: 14 studies investigated L-[11C]Methionine (11C-MET), one [11C]2-hydroxy-N,N,N-trimethylethanamium (11C-CH), six 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG), one 6-[18F] fluoro-L-DOPA (18F-DOPA), and three N-[(18F)Fluoromethyl]-2-hydroxy-N,N-dimethylethanaminium (18F-FCH). The 14 studies investigating MET included a total of 327 patients with 364 lesions. Sensitivity for the detection of a lesion in the correct quadrant had a pooled estimate of 69% (95% CI 60-78%). Heterogeneity was overall high with I2 of 51% (p = 0.01) for all 14 studies. Pooled PPV ranged from 91 to 100% with a pooled estimate of 98% (95% CI 96-100%). Of the other investigated tracers, 18-FCH seems the most promising with high diagnostic performance.ConclusionsThe results of our meta-analysis show that 11C-MET PET has an overall good sensitivity and PPV and may be considered a reliable second-line imaging modality to enable minimally invasive parathyroidectomy. Our literature review suggests that 18F-FCH PET may produce even greater accuracy and should be further investigated using both low-dose CT and MRI for anatomical correlation.