We compared 18F-fluorocholine hybrid positron emission tomography/X-ray computed tomography (FCH-PET/CT) with ultrasonography (US) and scintigraphy in patients with hyperparathyroidism and discordant, or equivocal results of US and 123I/99mTc-sesta-methoxyisobutylisonitrile (sestaMIBI) dual-phase parathyroid scintigraphy. FCH-PET/CT was performed in 17 patients with primary (n = 11) lithium induced (n = 1) or secondary hyperparathyroidism (1 dialyzed, 4 renal-transplanted).The reference standard was based on results of surgical exploration and histopathological examination. The results of imaging modalities were evaluated, on site and by masked reading, on per-patient and per-lesion bases.In a first approach, equivocal images/foci were considered as negative. On a per-patient level, the sensitivity was for US 38%, for scintigraphy 69% by open and 94% by masked reading, and for FCH-PET/CT 88% by open and 94% by masked reading. On a per-lesion level, sensitivity was for US 42%, for scintigraphy 58% by open and 83% by masked reading, and for FCH-PET/CT 88% by open and 96% by masked reading. One ectopic adenoma was missed by the 3 imaging modalities. Considering equivocal images/foci as positive increased the accuracy of the open reading of scintigraphy or of FCH-PET/CT, but not of US. FCH-PET/CT was significantly superior to US in all approaches, whereas it was more sensitive than scintigraphy only for open reading considering equivocal images/foci as negative (P = 0.04). FCH uptake was more intense in adenomas than in hyperplastic parathyroid glands. Thyroid lesions were suspected in 9 patients. They may induce false-positive results as in one case of oncocytic thyroid adenoma, or false-negative results as in one case of intrathyroidal parathyroid adenoma. Thyroid cancer (4 cases) can be visualized with FCH as with 99mTc-sestaMIBI, but the intensity of uptake was moderate, similar to that of parathyroid hyperplasia.This pilot study confirmed that FCH-PET/CT is an adequate imaging tool in patients with primary or secondary hyperparathyroidism, since both adenomas and hyperplastic parathyroid glands can be detected. The sensitivity of FCH-PET/CT was better than that of US and was not inferior to that of dual-phase dual-isotope 123I/99mTc-scintigraphy. Further studies should evaluate whether FCH could replace 99mTc-sestaMIBI as the functional agent for parathyroid imaging, but US would still be useful to identify thyroid lesions.

This prospective study aimed to compare the diagnostic performance of 18 F-fluorocholine and 18 F-FDG for detecting and staging hepatocellular carcinoma (HCC) in patients with chronic liver disease and suspected liver nodules. Methods: Whole-body PET/CT was performed in a random order at 10 min after injection of 4 MBq of 18 F-fluorocholine per kilogram and at 1 h after injection of 5 MBq of 18 F-FDG per kilogram. PET/CT results were read in a masked manner by 2 specialists, and diagnostic performance was assessed from the results of consensus masked reading. Those focal lesions appearing with increased or decreased activity, compared with background, on 18 F-fluorocholine PET/CT were considered positive for malignancy. The standard of truth was determined on a per-site basis using data from a histologic examination and a follow-up period of more than 6 mo; on a per-patient basis, the Barcelona criteria were also accepted as a proof of HCC in 5 patients. Results: Eighty-one patients were recruited; standard of truth was determined in 59 cases. HCC was diagnosed in 34 patients. Therefore, sensitivity was 88% for 18 F-fluorocholine and 68% for 18 F-FDG (P 5 0.07), and in 70 sites, sensitivity was 84% for 18 F-fluorocholine, significantly better than the 67% for 18 F-FDG (P 5 0.01). Of the 11 patients with well-differentiated HCC, 6 had a positive result with 18 F-fluorocholine alone, whereas 18 F-FDG was never positive alone; corresponding site-based sensitivity was 94% for 18 F-fluorocholine and 59% for 18 F-FDG (P 5 0.001). The detection rate of 18 sites corresponding to other malignancies was 78% for 18 F-fluorocholine and 89% for 18 F-FDG. In nonmalignant sites, 18 F-fluorocholine appeared less specific than 18 F-FDG (62% vs. 91% P , 0.01) because of uptake by focal nodular hyperplasia. Conclusion: 18 F-fluorocholine was significantly more sensitive than 18 F-FDG at detecting HCC, in particular in well-differentiated forms. In contrast, 18 F-FDG appeared somewhat more sensitive at detecting other malignancies and was negative in focal nodular hyperplasia. Thus 18 F-fluorocholine appears to be a useful PET/CT tracer for the detection and surveillance of HCC; however, performing PET/CT with both radiopharmaceuticals seems to be the best option.

As the main result of this pilot study, we show that in patients with hyperparathyroidism and with discordant or equivocal results on scintigraphy or on ultrasonography, adenomatous or hyperplastic parathyroid glands can be localized by FCH-PET/CT with good accuracy. Furthermore, FCH-PET/CT can solve discrepant results between preoperative ultrasonography and scintigraphy and has thus a potential as a functional imaging modality in the detection of abnormal parathyroid glands. Our preliminary results are encouraging and prompt us to further evaluate FCH-PET/CT as a functional imaging agent in patients with biochemical hyperparathyroidism.

6-Fluoro-(18F)-L-3,4-dihydroxyphenylalanine (FDOPA) is an amino acid analogue for positron emission tomography (PET) imaging which has been registered since 2006 in several European Union (EU) countries and by several pharmaceutical firms. Neuroendocrine tumour (NET) imaging is part of its registered indications. NET functional imaging is a very competitive niche, competitors of FDOPA being two well-established radiopharmaceuticals for scintigraphy, 123I-metaiodobenzylguanidine (MIBG) and 111In-pentetreotide, and even more radiopharmaceuticals for PET, including fluorodeoxyglucose (FDG) and somatostatin analogues. Nevertheless, there is no universal single photon emission computed tomography (SPECT) or PET tracer for NET imaging, at least for the moment. FDOPA, as the other PET tracers, is superior in diagnostic performance in a limited number of precise NET types which are currently medullary thyroid cancer, catecholamine-producing tumours with a low aggressiveness and well-differentiated carcinoid tumours of the midgut, and in cases of congenital hyperinsulinism. This article reports on diagnostic performance and impact on management of FDOPA according to the NET type, emphasising the results of comparative studies with other radiopharmaceuticals. By pooling the results of the published studies with a defined standard of truth, patient-based sensitivity to detect recurrent medullary thyroid cancer was 70 % [95 % confidence interval (CI) 62.1–77.6] for FDOPA vs 44 % (95 % CI 35–53.4) for FDG; patient-based sensitivity to detect phaeochromocytoma/paraganglioma was 94 % (95 % CI 91.4–97.1) for FDOPA vs 69 % (95 % CI 60.2–77.1) for 123I-MIBG; and patient-based sensitivity to detect midgut NET was 89 % (95 % CI 80.3–95.3) for FDOPA vs 80 % (95 % CI 69.2–88.4) for somatostatin receptor scintigraphy with a larger gap in lesion-based sensitivity (97 vs 49 %). Previously unpublished FDOPA results from our team are reported in some rare NET, such as small cell prostate cancer, or in emerging indications, such as metastatic NET of unknown primary (CUP-NET) or adrenocorticotropic hormone (ACTH) ectopic production. An evidence-based strategy in NET functional imaging is as yet affected by a low number of comparative studies. Then the suggested diagnostic trees, being a consequence of the analysis of present data, could be modified, for some indications, by a wider experience mainly involving face-to-face studies comparing FDOPA and 68Ga-labelled peptides.

BackgroundPositron emission tomography-computed tomography (PET/CT) with 18F-fluorocholine (FCH) is routinely performed in patients with prostate cancer. In this clinical context, foci of FCH uptake in the head or in the neck were considered as incidentalomas, except for those suggestive of multiple bone metastases.ResultsIn 8 patients the incidental focus corresponded to a benign tumour. The standard of truth was histology in two cases, correlative imaging with MRI in four cases, 99mTc-SestaMIBI scintigraphy, ultrasonography and biochemistry in one case and biochemistry including PTH assay in one case. The final diagnosis of benign tumours consisted in 3 pituitary adenomas, 2 meningiomas, 2 hyperfunctioning parathyroid glands and 1 thyroid adenoma.Malignancy was proven histologically in 2 other patients: 1 papillary carcinoma of the thyroid and 1 cerebellar metastasis.ConclusionsTo the best of our knowledge, FCH uptake by pituitary adenomas or hyperfunctioning parathyroid glands has never been described previously. We thus discuss whether there might be a future indication for FCH PET/CT when one such tumour is already known or suspected: to detect a residual or recurrent pituitary adenoma after surgery, to guide surgery or radiotherapy of a meningioma or to localise a hyperfunctioning parathyroid gland. In these potential indications, comparative studies with reference PET tracers or with 99mTc-sestaMIBI in case of hyperparathyroidism could be undertaken.

The aims of this cohort study were to evaluate initial tumor hypoxia in metastatic renal cell carcinoma (mRCC) and its changes after sunitinib treatment, using 18 F-fluoromisonidazole PET/CT, and investigate the possible prognostic value of initial tumor hypoxia or its changes under sunitinib therapy. Methods: Antiangiogenic-naive patients with mRCC were prospectively enrolled in this cohort study. Before initiation of sunitinib, CT defined up to 10 targets that were assessed at 1 and 6 mo according to the response evaluation criteria in solid tumors (RECIST). Pretreatment target uptake of 18 F-fluoromisonidazole was compared with uptake at 1 mo. Targets were considered hypoxic when their maximal standard uptake value was above mean blood value 1 2 SDs. Hypoxic volumes were also computed. Relationships between initial hypoxia status, initial degree of hypoxia, its change at 1 mo, and overall or progression-free survival (OS and PFS, respectively) were assessed by survival analysis. Results: Fifty-three patients were included. Median follow-up was 16.8 mo. 18 F-fluoromisonidazole uptake significantly decreased in initially hypoxic target metastases but did not change in others (222%, P , 10 24 , vs. 11.5%, P 5 0.77; P 5 10 23 between groups). Seventy-five percent of patients with hypoxic metastases were free of progressive disease at 4.8 mo (95% confidence interval, 2.99-11.83), compared with 11.3 mo (95% confidence interval, 3.08-36.9) for other patients (P 5 0.02), whereas OS was not significantly different. Changes in tumor hypoxia were not related to PFS or OS. Conclusion: Sunitinib reduced hypoxia in initially hypoxic RECIST target metastases but did not induce significant hypoxia in nonhypoxic RECIST target metastases. Patients with initially hypoxic targets have shorter PFS than others.

FDOPA-PET appears to be a major tool for the management of carcinoid tumors with excellent diagnostic performances and induced relevant changes in patient management. FDOPA-PET was less sensitive and less useful for the management of noncarcinoid tumors.

Key Points• CLEC-1 is restricted to CD16 2 myeloid DCs in human blood and acts as an inhibitory receptor to restrain downstream Th17 activation.• CLEC-1-deficient rats highlight an in vivo function for CLEC-1 in preventing excessive T-cell priming and effector Th responses.Dendritic cells (DCs) represent essential antigen-presenting cells that are critical for linking innate and adaptive immunity, and influencing T-cell responses. Among pattern recognition receptors, DCs express C-type lectin receptors triggered by both exogenous and endogenous ligands, therefore dictating pathogen response, and also shaping T-cell immunity.We previously described in rat, the expression of the orphan C-type lectin-like receptor-1 (CLEC- 1) by DCs and demonstrated in vitro its inhibitory role in downstream T helper 17 (Th17)activation. In this study, we examined the expression and functionality of CLEC-1 in human DCs, and show a cell-surface expression on the CD16 2 subpopulation of blood DCs and on monocytederived DCs (moDCs). CLEC-1 expression on moDCs is downregulated by inflammatory stimuli and enhanced by transforming growth factor b. Moreover, we demonstrate that CLEC-1 is a functional receptor on human moDCs and that although not modulating the spleen tyrosine kinase-dependent canonical nuclear factor-kB pathway, represses subsequent Th17 responses.Interestingly, a decreased expression of CLEC1A in human lung transplants is predictive of the development of chronic rejection and is associated with a higher level of interleukin 17A (IL17A). Importantly, using CLEC-1-deficient rats, we showed that disruption of CLEC-1 signaling led to an enhanced Il12p40 subunit expression in DCs, and to an exacerbation of downstream in vitro and in vivo CD4 1 Th1 and Th17 responses. Collectively, our results establish a role for CLEC-1 as an inhibitory receptor in DCs able to dampen activation and downstream effector Th responses. As a cell-surface receptor, CLEC-1 may represent a useful therapeutic target for modulating T-cell immune responses in a clinical setting.