Preoperative molecular imaging is paramount to direct surgery in primary hyperparathyroidism (pHPT). We investigated the diagnostic performance of ¹⁸F-fluorocholine (¹⁸F-FCH) PET/CT compared with ¹¹C-methionine (¹¹C-MET) PET/CT for localization of hyperfunctioning parathyroid tissue in patients with pHPT and negative or inconclusive ^99mTc-sestaMIBI (^99mTc-MIBI) SPECT findings. Methods: Fifty-eight patients with biochemical evidence of pHPT and negative or inconclusive ^99mTc-MIBI SPECT findings were referred for presurgical detection and localization of hyperfunctioning parathyroid tissue by ¹¹C-MET and ¹⁸F-FCH PET/CT. The PET/CT results were classified into 3 categories (positive, inconclusive, or negative) based on the nodular aspect of tracer uptake and the visualization of corresponding nodules on CT. The PET/CT results were correlated with the surgical and histopathologic findings, which were used as the gold standard. Results: Fifty-three patients were included for analysis. ¹⁸F-FCH PET/CT was positive in 39 patients (74%), inconclusive in 5 (9%), and negative in 9 (17%), compared with 25 (47%), 12 (23%), and 16 (30%), respectively, for ¹¹C-MET PET/CT. ¹⁸F-FCH localized 11 additional foci (6 positive and 5 inconclusive), compared with ¹¹C-MET. Twenty-six patients (sex ratio, 10/16 M/F) underwent surgery, with resection of 31 lesions (22 adenomas, 6 hyperplastic glands, and 3 carcinomas) and 1 normal gland. At follow-up, 21 patients (81%) were considered cured after surgery, whereas 3 patients (12%) had persistence of hypercalcemia. With inconclusive cases being considered negative, ¹⁸F-FCH PET/CT correctly localized 26 lesions in 24 of 26 patients (92%), compared with 16 lesions in 15 of 26 patients (58%) localized by ¹¹C-MET PET/CT. Per-patient-based sensitivity and positive predictive value were 96% and 96%, respectively, for ¹⁸F-FCH and 60% and 94%, respectively, for ¹¹C-MET (P < 0.0001). Per-lesion-based sensitivity and positive predictive value were 84% and 90%, respectively, for ¹⁸F-FCH and 52% and 94%, respectively, for ¹¹C-MET (P < 0.0001). Conclusion: In the presence of biochemical evidence of pHPT with negative or inconclusive ^99mTc-MIBI SPECT findings, ¹⁸F-FCH PET/CT performs better than ¹¹C-MET PET/CT for the detection of pathologic parathyroid tissue, allowing localization of parathyroid adenoma or hyperplasia in 96% of patients.

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