Performance of [18F]fluorocholine PET/CT in MEN1-related primary hyperparathyroidism before initial surgery or for persistent/recurrent disease.

PURPOSE: The aims of the study were to evaluate the performance and robustness of [18F]fluorocholine PET/CT in detecting hyperfunctioning parathyroid glands in MEN1-related primary hyperparathyroidism (pHPT) at different stages of their disease. METHODS: Retrospective French multicenter study including patients with MEN1 pHPT who underwent [18F]fluorocholine PET/CT at initial diagnosis or for evaluation of persistent/recurrent disease. PET/CT were independently reviewed by two readers in a blinded manner. The assessment of PET/CT on a per-patient basis was assessed using a comprehensive set of criteria that considered pathological findings or agreement with alternative diagnostic methods in non-operated patients. The secondary objectives included the analysis of the performance of PET/CT at a per-lesion level, with reference to a pathological Gold Standard, and examining its interobserver reproducibility. RESULTS: A total of 71 MEN1 patients were included (73 PET/CT) in the study. At the per-patient level (entire cohort), [18F]fluorocholine PET/CT sensitivity ranged from 98.5 to 100% among the different readers. An average of 1.77 glands per PET was described, with 2.35 glands at the initial diagnosis (n = 23) and 1.5 in previously operated cases (n = 50). PET/CT detected more lesions than conventional imaging work-up (neck ultrasound and/or scintigraphy). At the per-lesion level (41 operated patients), sensitivity ranged across different readers from 84.4 to 87%, and specificity ranged from 94.7 to 98.8%. At initial diagnosis, all patients that exhibited 3 or more abnormal glands on PET underwent subtotal parathyroidectomy while 7 out of 13 patients with 1 or 2 gland abnormalities on PET underwent less than subtotal parathyroidectomy. Finally, the degree of inter-observer agreement was high. CONCLUSION: [18F]fluorocholine PET/CT is a reliable and robust imaging modality for the evaluation of MEN1-related pHPT and could guide surgeons in achieving the optimal benefit-risk ratio. This study gives a great impetus for its adoption as a primary diagnostic tool in this context.

The relationship between 18F-FCH uptake intensity and cell content in parathyroid lesions.

PURPOSE: To investigate the relationship between cell content and histopathological features of parathyroid lesions and 18F-FCH uptake intensity on PET/CT images. METHODS: Patients with primary hyperparathyroidism (age > 18) who were referred to 18F-FCH PET/CT were involved. All patients underwent parathyroidectomy. Correlation of SUVmax with following factors were statistically analysed: serum PTH, Ca, P levels and histopathological parameters, total absolute amounts of chief cell, oxyphyllic cell and clear cell components calculated by the multiplication of the volume of the parathyroid lesion and the percentage of each type of cell content (called as Absolutechief, Absoluteoxyphyllic and Absoluteclear reflecting the total amount of each cell group). RESULTS: A total of 34 samples from 34 patients (6M, 28F, mean age: 53.32 ± 15.15, min: 14, max: 84) who had a positive 18F-FCH PET/CT localizing at least one parathyroid lesion were involved. In the whole study group, SUVmax was found to be correlated with the greatest diameter and volume of the lesion and Absolutechief (p = 0.004, p = 0.002 and p = 0.035, respectively). In the subgroup analysis of 28 samples with longest diameter > 1 cm, the correlation between SUVmax and Absolutechief remained significant (p = 0.036) and correlation between SUVmax and volume and longest diameter became stronger (p = 0.011 and p > 0.001, respectively). No correlation was found between SUVmax and Absoluteoxyphyllic or Absoluteclear. CONCLUSIONS: There might be a relationship between 18F-FCH uptake intensity and chief cell content in patients with parathyroid adenoma. Further studies with larger patient groups would be beneficial to support the data.

Narrative review of PET/CT performances at biochemical recurrence in prostate cancer after radical prostatectomy and impact on patient disease management: Revue narrative à propos des performances de la TEP/TDM en cas de récidive biochimique après prostatectomie radicale dans le cancer de la prostate et impact sur la prise en charge des patients.

Patients treated by radical prostatectomy (RP) for localized prostate cancer (PCa) may experience biochemical recurrence (BCR) in approximately 30% of cases. Recently, advances in imaging modalities and in particular Positron-Emission Tomography with computed tomography (PET/CT) imaging allow for better detection and characterization of lesions outside the prostatic bed at recurrence. Thus, treatment at BCR can be significantly improved by a tailored strategy based on new generation imaging. A more precise and accurate staging of the disease at recurrence paves the way to more appropriate treatment, potentially translating into better survival outcomes of these patients. This review therefore highlights the interest of PET/CT at the time of BCR, its superiority over standard imaging in terms of staging, and its impact on guiding the different therapeutic possibilities depending on the site, number, and volumes of recurrence. Indeed, we will discuss below about different strategies and their indications: salvage radiotherapy of the prostate bed, systemic therapies, stereotactic body radiotherapy and others therapeutical strategies. The various innovative approaches based on PET/CT implementation are partly underway within protocol trials to prove their benefits on clinically meaningful endpoints. © 2022 Elsevier Masson SAS. All rights reserved.

DIAGNOSTIC PERFORMANCES OF 18F-FLUOROCHOLINE POSITRON EMISSION TOMOGRAPHY-COMPUTED TOMOGRAPHY AND REPEATED ULTRASONOGRAPHY IN DETECTING UNDEFINED LESIONS IN PATIENTS WITH AN INDICATION FOR PRIMARY HYPERPARATHYROIDISM SURGERY.

Context: 18F-fluorocholine (FCH) has been used as a positron emission tomography (PET) tracer in the localization of hyper-functioning parathyroid glands (HPGs). Objective: We performed this methodological study to evaluate the diagnostic performance of 18F-FCH PET/computerized tomography (CT) and repeated ultrasonography (USG) in detecting unidentified lesions in patients with primary hyperparathyroidism (PHPT). Design: In this retrospective methodological study, we studied the diagnostic performance of 18F-FCH PET/CT and a repeated USG in detecting unidentified parathyroid lesions. Subjects and Methods: Twenty-eight patients who were diagnosed with PHPT, had an indication for surgery following the current guidelines and had no identified lesion on 99mTc-MIBI SPECT/CT, USG, or other imaging methods than 18F-FCH PET/CT, included in the study. Results: While lesions were detected in 26 patients via 18F-FCH PET/CT among 28 patients [92.9% (95% CI: 76.6%-99.1%)], the lesion detection rate was 95.7% (95% CI: 78.1%-99.9%) in 23 patients who underwent a repeated USG. The sensitivity and the accuracy of both 18F-FCH PET/CT and repeated USG were 95.2% (95% CI: 76.2%-99.9%) and 95.0 (95% CI: 75.1%-99.9%), respectively. Conclusions: This study supports that the combination of 18F-FCH PET/CT and repeated USG has promising potential for being an imaging technique for early detection and localization of HPGs.

Survey by the French Medicine Agency (ANSM) of the imaging protocol, detection rate, and safety of 68Ga-PSMA-11 PET/CT in the biochemical recurrence of prostate cancer in case of negative or equivocal 18F-fluorocholine PET/CT: 1084 examinations.

INTRODUCTION: Despite growing evidence of a superior diagnostic performance of 68Ga-PSMA-11 over 18F-fluorocholine (FCH) PET/CT, the number of PET/CT centres able to label on site with gallium-68 is still currently limited. Therefore, patients with biochemical recurrence (BCR) of prostate cancer frequently undergo FCH as the 1st-line PET/CT. Actually, the positivity rate (PR) of a second-line PSMA-11 PET/CT in case of negative FCH PET/CT has only been reported in few short series, in a total of 185 patients. Our aims were to check (1) whether the excellent PR reported with PSMA-11 is also obtained in BCR patients whose recent FCH PET/CT was negative or equivocal; (2) in which biochemical and clinical context a high PSMA-11 PET/CT PR may be expected in those patients, in particular revealing an oligometastatic pattern; (3) whether among the various imaging protocols for PSMA-11 PET/CT used in France, one yields a significantly highest PR; (4) the tolerance of PSMA-11. PATIENTS AND METHODS: Six centres performed 68Ga-PSMA-11 PET/CTs during the first 3 years of its use in France. Prior to each PET/CT, the patient's data were submitted prospectively for authorisation to ANSM, the French Medicine Agency. The on-site readings of 1084 PSMA-11 PET/CTs in BCR patients whose recent FCH PET/CTs resulted negative or equivocal were pooled and analysed. RESULTS: (1) The overall PR was 68%; for a median serum PSA level (sPSA) of 1.7 ng/mL, an oligometastatic pattern (1-3 foci) was observed in 31% of the cases overall; (2) PR was significantly related to sPSA (from 41% if < 0.2 ng/mL to 81% if ≥ 2 ng/mL), to patients' age, to initial therapy (64% if prostatectomy vs. 85% without prostatectomy due to frequent foci in the prostate fossa), to whether FCH PET/CT was negative or equivocal (PR = 62% vs. 82%), and to previous BCR (PR = 63% for 1st BCR vs. 72% in case of previous BCR); (3) no significant difference in PR was found according to the imaging protocol: injected activity, administration of a contrast agent and/or of furosemide, dose length product, one single or multiple time points of image acquisition; (4) no adverse event was reported after PSMA-11 injection, even associated with a contrast agent and/or furosemide. CONCLUSION: Compared with the performance of PSMA-11 PET/CT in BCR reported independently of FCH PET/CT in 6 large published series (n > 200), the selection based on FCH PET/CT resulted in no difference of PSMA-11 PR for sPSA < 1 ng/mL but in a slightly lower PR for sPSA ≥ 1 ng/mL, probably because FCH performs rather well at this sPSA and very occult BCR was over-represented in our cohort. An oligometastatic pattern paving the way to targeted therapy was observed in one fourth to one third of the cases, according to the clinico-biochemical context of the BCR. Systematic dual or triple acquisition time points or administration of a contrast agent and/or furosemide did not bring a significant added value for PSMA-11 PET/CT positivity and should be decided on individual bases.

Misleading localization by 18F-fluorocholine PET/CT in familial hypocalciuric hypercalcemia type-3: a case report.

BACKGROUND: Familial hypocalciuric hypercalcemia (FHH) is a heterogeneous autosomal-dominant disorder of calcium hemostasis that may be difficult to distinguish clinically from mild primary hyperparathyroidism. Loss-of-function mutations mainly involving Arg15 residue of the adaptor-related protein complex 2, sigma subunit 1 (AP2S1) cause a rarer, more recently recognized form of FHH, FFH type-3. Recently, 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) showed superior sensitivity to conventional imaging in localizing parathyroid adenomas. We report a new FFH type-3 patient who underwent unnecessary parathyroidectomy in association with misleading FCH-PET/CT imaging. CASE PRESENTATION: A 29-year old woman was initially evaluated for parathyroid hormone (PTH)-dependent hypercalcemia in 2013. Medical history was positive only for chronic constipation and malaise with no personal or family history of hypercalcemia, kidney stones, or neck surgery. Over seven years, serum calcium level was 2.51-2.89 mmol/L with concomitant PTH level of 58.7-94.8 mmol/L. Serum phosphate levels were in the low/low normal range. Serum creatinine and magnesium levels were normal. 25-hydroxy vitamin D level was 13 nmol/L. 24-hour urine calcium level was 1.92 mmol/day but increased to 6.99 mmol/day after treatment with cholecalciferol 1000 IU daily. Bone mineral density and renal ultrasound were normal. Parathyroid ultrasound showed two hypoechoic nodules inferior to the left and right thyroid lobes; however, 99mtechnitium-sestamibi scans (2013, 2016, 2018) were negative. FCH-PET/CT (2019) showed focal uptake co-localizing with the nodule inferior to the left thyroid lobe. The patient underwent left inferior parathyroidectomy and pathology was consistent with parathyroid hyperplasia. However, postoperatively, serum calcium and PTH levels remained elevated and FCH-PET/CT and ultrasound showed persistence of the uptake/nodule. Whole exome sequencing showed Arg15Cys mutation in the AP2S1 gene characteristic of FHH type-3. CONCLUSIONS: In this new case of FHH type-3, FCH-PET/CT failed to localize to the hyperplastic parathyroid glands and localized instead to apparently a lymph node. This, together with increased urinary calcium after vitamin D supplementation, led to unnecessary parathyroidectomy. Given the increasingly lower cost of genetic testing and the cost of follow up and unnecessary surgery, it may prudent to include genetic testing for FHH early on in patients with mild PTH-dependent hypercalcemia.

18F-Fluorocholine PET uptake correlates with pathologic evidence of recurrent tumor after stereotactic radiosurgery for brain metastases.

PURPOSE: Radiographic changes of brain metastases after stereotactic radiosurgery (SRS) can signify tumor recurrence and/or radiation necrosis (RN); however, standard imaging modalities cannot easily distinguish between these two entities. We investigated whether 18F-Fluorocholine uptake in surgical samples of the resected lesions correlates with pathologic evidence of recurrent tumor and PET imaging. METHODS: About 14 patients previously treated with SRS that developed radiographic changes were included. All patients underwent a preoperative 40-min dynamic PET/CT concurrent with 392 ± 11 MBq bolus injection of 18F-Fluorocholine. 18F-Fluorocholine pharmacokinetics were evaluated by standardized uptake value (SUV), graphical analysis (Patlak plot; KiP) and an irreversible two-compartment model (K1, k2, k3, and Ki). 12 out of 14 patients were administered an additional 72 ± 14 MBq injection of 18F-Fluorocholine 95 ± 26 minutes prior to surgical resection. About 113 resected samples from 12 patients were blindly reviewed by a neuropathologist to assess the viable tumor and necrotic content, microvascular proliferation, reactive gliosis, and mono- and polymorphonuclear inflammatory infiltrates. Correlation between these metrics 18F-Fluorocholine SUV was investigated with a linear mixed model. Comparison of survival distributions of two groups of patients (population median split of PET SUVmax) was performed with the log-rank test. RESULTS: Exactly 10 out of 12 patients for which surgical samples were acquired exhibited pathologic recurrence. Strong correlation was observed between SUVmax as measured from a surgically removed sample with highest uptake and by PET (Pearson's r = 0.66). Patients with 18F-Fluorocholine PET SUVmax > 6 experienced poor survival. Surgical samples with viable tumor had higher 18F-fluorocholine uptake (SUV) than those without tumor (4.5 ± 3.7 and 2.6 ± 3.0; p = 0.01). 18F-fluorocholine count data from surgical samples is driven not only by the percentage viable tumor but also by the degree of inflammation and reactive gliosis (p ≤ 0.02; multivariate regression). CONCLUSIONS: 18F-Fluorocholine accumulation is increased in viable tumor; however, inflammation and gliosis may also lead to elevated uptake. Higher 18F-Fluorocholine PET uptake portends worse prognosis. Kinetic analysis of dynamic 18F-Fluorocholine PET imaging supports the adequacy of the simpler static SUV metric.

Superior performance of 18F-fluorocholine digital PET/CT in the detection of parathyroid adenomas.

OBJECTIVE: To compare detectability of hyperfunctioning parathyroid tissue (HPT) by digital and analog 18F-fluorocholine PET/CT in patients with primary hyperparathyroidism and negative/inconclusive 99mTc-MIBI scintigraphy-SPECT/CT. MATERIALS AND METHODS: Thirty-three patients with primary hyperparathyroidism and negative/inconclusive 99mTc-MIBI scintigraphy-SPECT/CT were prospectively included. All patients accepted to be scanned by digital and analog PET/CT in the same imaging session after a single injection of 18F-fluorocholine. Three nuclear medicine physicians evaluated the digital and analog PET/CT datasets to assess the detection rate of HPT. Maximum standard uptake values (SUVmax) of HPT and locoregional lymph nodes were measured in both systems. RESULTS: HPT was detected in 30/33 patients by the digital system, whereas it was detected in 22/33 patients by the analog system (p < 0.01). Moreover, in 21 of these 33 patients, both systems detected one focal 18F-fluorocholine uptake, and in one patient the digital system detected two foci. Histopathology demonstrated HPT in 32 patients and it was inconclusive in one patient. The digital PET/CT detected HPT in 29 of the 32 patients, and the analog system in 22 of the 32 (p < 0.01). All HPT suspected lesions resected and detected only by the digital system (n = 8) were < 10 mm (7.5 ± 1.3 mm), while those detected by both systems (n = 22) were > 10 mm (13 ± 3.8 mm). SUVmax of HPT lesions was significantly higher than SUVmax of locoregional lymph node independently of the PET/CT system used (4.5 ± 1.9 vs. 2.9 ± 1.3, p < 0.0001). CONCLUSIONS: Digital PET/CT offers superior performance over analog system in patients with suspected HPT and previous negative/inconclusive imaging examinations, particularly in sub-centimeter lesions. SUVmax can help in the differentiation between HTP and locoregional lymph nodes.

Baseline and Post-treatment 18F-Fluorocholine PET/CT Predicts Outcomes in Hepatocellular Carcinoma Following Locoregional Therapy.

BACKGROUND AND AIMS: 18F-fluorocholine positron emission tomography/computed tomography (18F-FCH PET/CT) is an emerging functional imaging technique in the diagnosis and management of hepatocellular carcinoma (HCC). The aim of this study was to assess the ability of a pre- and post-treatment 18F-FCH PET/CT to predict prognosis and treatment response in early-stage HCC. METHODS: Patients with early- or intermediate-stage HCC planned for locoregional therapy were prospectively enrolled. Baseline demographic and tumor information was collected and baseline and post-treatment 18F-FCH PET/CT performed. Maximum standardized uptake values (SUVmax) were determined for each HCC lesion, and the difference between baseline and post-treatment SUVmax values were compared with progression-free survival outcomes. RESULTS: A total of 29 patients with 39 confirmed HCC lesions were enrolled from a single clinical center. Patients were mostly men (89.7%) with hepatitis C or alcohol-related cirrhosis (65.5%) and early-stage disease (89.7%). Per-patient and per-lesion sensitivity of 18F-FCH PET/CT was 72.4% and 59.0%, respectively. A baseline SUVmax < 13 was associated with a superior median progression-free survival compared with an SUVmax of > 13 (17.7 vs. 5.1 months; p = 0.006). A > 45% decrease in SUVmax between baseline and post-treatment 18F-FCH PET/CT ("responders") was associated with a superior mean progression-free survival than a percentage decrease of < 45% ("non-responders," 36.1 vs. 11.6 months; p = 0.034). CONCLUSIONS: Baseline and post-treatment 18F-FCH PET/CT predicts outcomes in early-stage HCC undergoing locoregional therapy. This technique may identify patients with an objective response post-locoregional therapy who would benefit from further therapy.

Salvage extended field or involved field nodal irradiation in 18F-fluorocholine PET/CT oligorecurrent nodal failures from prostate cancer.

PURPOSE: The concept of metastasis-directed therapy for nodal oligorecurrences with stereotactic body radiotherapy is increasingly accepted. Hence, the comparison between salvage extended field radiotherapy (s-EFRT) and salvage involved field radiotherapy (s-IFRT) in patients with 18F-fluorocholine (FCH) PET/CT+ nodal oligorecurrences from prostate cancer is worthy of investigation. METHODS: Patients with oligorecurrent nodes on FCH PET/CT treated with salvage radiotherapy between 2009 and 2017 in a single tertiary cancer centre were selected for this study. Patients treated with s-IFRT were compared with those treated with s-EFRT. Toxicities and times to failure (TTF) were compared between the two groups. RESULTS: The study included 62 patients with positive lymph nodes only who underwent FCH PET/CT for a rising PSA level after radical prostatectomy or radiotherapy. Of these patients, 35 had s-IFRT and 27 had s-EFRT. After a median follow-up of 41.8 months (range 5.9-108.1 months), no differences were observed in acute or late gastrointestinal and genitourinary toxicities of grade 2 or more between the two groups. The 3-year failure rates were 55.3% (95% CI 37.0-70.3%) in the s-IFRT group and 88.3% (95% CI 66.9-96.1%) in the s-EFRT group (p = 0.0094). In multivariate analysis of TTF, an interval of >5 years was significantly correlated with better outcomes (HR = 0.33, 95% CI 0.13-0.86, p = 0.023). There was a strong trend toward better outcomes with s-EFRT even after adjusting for concomitant androgen-deprivation therapy (HR = 0.38, 95% CI 0.12-1.27, p = 0.116). CONCLUSION: FCH PET-positive node-targeted s-EFRT is feasible with low rates of toxicity and longer TTF, suggesting that oligorecurrent nodal disease diagnosed on FCH PET is unlikely.

Challenging pre-surgical localization of hyperfunctioning parathyroid glands in primary hyperparathyroidism: the added value of 18F-Fluorocholine PET/CT.

PURPOSE: To evaluate the added value of 18F-Fluorocholine (18F-FCH) PET/CT in presurgical imaging of patients with primary hyperparathyroidism (HPT) and challenging localization of the hyper-functioning parathyroid glands. METHODS: We included 27 consecutive patients with primary HPT (19 F; median age: 58 years), with either (i) non-conclusive pre-surgical localization with 99mTc-sestaMIBI scintigraphy and neck ultrasonography (US), (ii) recurrence of previously operated HPT, or (iii) familiar HPT with a suspicion of multiple gland disease. Histological findings and resolution of HPT were considered as the gold standard. RESULTS: 18F-FCH PET/CT was positive in 24/27 patients. Twenty-one patients underwent surgery with 27 resected lesions (14 adenomas, 11 hyperplastic glands, two hyper-functioning histologically normal glands), with resolution of HPT in 19/21 patients (90%). 18F-FCH PET/CT localized 22 lesions in 17/21 patients (per patient: sensitivity 81%, positive predictive value (PPV) 94%; per gland: sensitivity 76%, PPV 85%, specificity 91%, negative predictive value (NPV) 86%). 18F-FCH PET/CT found eight lesions which were undetectable on both 99mTc-sestaMIBI scintigraphy and US. In patients with a familial HPT and/or a multiple gland disease, sensitivity was 100 and 79% on a per-patient and a per-gland analysis respectively, while NPV was 63%. In six patients with a persistence or recurrence of previously treated HPT, 18F-FCH PET/CT localized all lesions, both in sporadic and familiar disease. CONCLUSIONS: 18F-FCH PET/CT is a promising modality in challenging pre-surgical localization of hyper-functioning parathyroid glands, such as inconclusive standard imaging, recurrence after surgery, or suspected multiple gland disease.

18F-Fluorocholine PET/CT in the assessment of primary hyperparathyroidism compared with 99mTc-MIBI or 99mTc-tetrofosmin SPECT/CT: a prospective dual-centre study in 100 patients.

PURPOSE: In this prospective study we compared the accuracy of 18F-fluorocholine PET/CT with that of 99mTc-MIBI or99mTc-tetrofosmin SPECT/CT in the preoperative detection of parathyroid adenoma in patients with primary hyperparathyroidism. We also assessed the value of semiquantitative parameters in differentiating between parathyroid hyperplasia and adenoma. METHODS: Both 18F-fluorocholine PET/CT and 99mTc-MIBI/tetrofosmin SPECT/CT were performed in 100 consecutive patients with biochemical evidence of primary hyperparathyroidism. At least one abnormal focus on either 18F-fluorocholine or 99mTc-MIBI/tetrofosmin corresponding to a parathyroid gland or ectopic parathyroid tissue was considered as a positive finding. In 76 patients with positive findings on at least one imaging modality, surgical exploration was performed within 6 months, and the results were related to histopathological findings and clinical and laboratory findings at 3-6 months as the standard of truth. In 24 patients, no surgery was performed: in 18 patients with positive imaging findings surgery was refused or considered risky, and in 6 patients imaging was negative. Therefore, data from 82 patients (76 undergoing surgery, 6 without surgery) in whom the standard of truth criteria were met, were used in the final analysis. RESULTS: All patients showed biochemical evidence of primary hyperparathyroidism with a mean serum calcium level of 2.78 ± 0.34 mmol/l and parathormone (PTH) level of 196.5 ± 236.4 pg/ml. The study results in 76 patients with verified histopathology and 3 patients with negative imaging findings were analysed. Three of six patients with negative imaging showed normalized serum PTH and calcium levels on laboratory follow-up at 3 and 6 months, and the results were considered true negative. In a patient-based analysis, the detection rate with 18F-fluorocholine PET/CT was 93% (76/82), but was only 61% (50/82) with 99mTc-MIBI/tetrofosmin SPECT/CT. In a lesion-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of 18F-fluorocholine PET/CT in the detection of parathyroid adenoma were 93.7%, 96.0%, 90.2%, 97.4% and 95.3%, respectively, and of 99mTc-MIBI/tetrofosmin SPECT/CT were 60.8%, 98.5%, 94.1%, 86.3% and 87.7%, respectively. Although 18F-fluorocholine PET-positive adenomatous lesions showed higher SUVmax values than the hyperplastic glands (6.80 ± 3.78 vs. 4.53 ± 0.40) in the semiquantitative analysis, the difference was not significant (p = 0.236). The mean size (measured as the length of the greatest dimension) and weight of adenomas were 15.9 ± 7.6 mm (median 15 mm, range 1-40 mm) and 1.71 ± 1.86 g (median 1 g, range: 0.25-9 g), respectively. Among the analysed parameters including serum calcium and PTH and the size and weight of parathyroid adenomas, size was significantly different between patients with negative 99mTc-MIBI/tetrofosmin SPECT/CT and those with positive 99mTc-MIBI/tetrofosmin SPECT/CT (mean size 13.4 ± 7.6 mm vs. 16.9 ± 7.4 mm, respectively; p = 0.042). CONCLUSION: In this prospective study, 18F-fluorocholine PET/CT showed promise as a functional imaging modality, being clearly superior to 99mTc-MIBI/tetrofosmin SPECT/CT, especially in the detection and localization of small parathyroid adenomas in patients with primary hyperparathyroidism. SUVmax was higher in parathyroid adenomas than in hyperplasia. However, further evaluation of this modality is needed.

PET and PET/CT with radiolabeled choline in prostate cancer: a critical reappraisal of 20 years of clinical studies.

We here aim to provide a comprehensive and critical review of the literature concerning the clinical applications of positron emission tomography/computed tomography (PET/CT) with radiolabeled choline in patients with prostate cancer (PCa). We will initially briefly summarize the historical context that brought to the synthesis of [11C]choline, which occurred exactly 20 years ago. We have arbitrarily grouped the clinical studies in three different periods, according to the year in which they were published and according to their relation with their applications in urology, radiotherapy and oncology. Studies at initial staging and, more extensively, studies in patients with biochemical failure, as well as factors predicting positive PET/CT will be reviewed. The capability of PET/CT with radiolabeled choline to provide prognostic information on PCa-specific survival will also be examined. The last sections will be devoted to the use of radiolabeled choline for monitoring the response to androgen deprivation therapy, radiotherapy, and chemotherapy. The accuracy and the limits of the technique will be discussed according to the information available from standard validation processes, including biopsy or histology. The clinical impact of the technique will be discussed on the basis of changes induced in the management of patients and in the evaluation of the response to therapy. Current indications to PET/CT, as officially endorsed by guidelines, or as routinely performed in the clinical practice will be illustrated. Emphasis will be made on methodological factors that might have influenced the results of the studies or their interpretation. Finally, we will briefly highlight the potential role of positron emission tomography/magnetic resonance and of new radiotracers for PCa imaging.

[PET/CT and biochemical recurrence of prostate adenocarcinoma: Added value of 68Ga-PSMA-11 when 18F-fluorocholine is non-contributive]. / TEP/TDM et récidive biologique d'adénocarcinome prostatique : apport du 68Ga-PSMA-11 lorsque la 18F-fluorocholine n'est pas contributive.

INTRODUCTION: Since April 201, we have introduced PET/CT using a ligand of prostate-specific membrane antigen labeled with gallium-68 (PSMA-11). We aimed to evaluate its positivity rate and impact in patients presenting biochemical recurrence of prostate cancer whose 18F-fluorocholine (FCH) PET/CT was non-contributive. PATIENTS AND METHOD: Patients were prospectively included between April and December 2016. PET/CT was performed 60min after injection of 2MBq/kg of body mass of 68Ga-PSMA-11. Three anatomical areas were considered: prostatic lodge, pelvic lymph nodes and distant locations. The impact of PSMA-11 PET/CT was assessed by comparing changes in therapeutic strategy decided during multidisciplinary meeting. RESULTS: Thirty-three patients were included. The mean PSA serum level measured on the month of the PSMA-11 PET/CT was 2,8ng/mL. Twenty-five (76%) PSMA-11 PET/CT were positive, 7 (21%) negative and 1 (3%) equivocal. Of 11 patients whose FCH PET/CT showed equivocal foci, PSMA-11 PET/CT confirmed those foci in 5 cases. Follow-up was available for 18 patients (55%). PSMA-11 PET/CT results led to a change in management in 12 patients (67%). CONCLUSION: 68Ga-PSMA-11 PET/CT is useful in detecting recurrence of prostate cancer, by identifying residual disease which was not detected on other imaging modalities and by changing management of 2 patients out of 3. LEVEL OF EVIDENCE: 5.

Comparison of meta-analyses among elastosonography (ES) and positron emission tomography/computed tomography (PET/CT) imaging techniques in the application of prostate cancer diagnosis.

The early diagnosis of prostate cancer (PCa) appears to be of vital significance for the provision of appropriate treatment programs. Even though several sophisticated imaging techniques such as positron emission tomography/computed tomography (PET/CT) and elastosonography (ES) have already been developed for PCa diagnosis, the diagnostic accuracy of these imaging techniques is still controversial to some extent. Therefore, a comprehensive meta-analysis in this study was performed to compare the accuracy of various diagnostic imaging methods for PCa, including 11C-choline PET/CT, 11C-acetate PET/CT, 18F-fluorocholine PET/CT, 18F-fluoroglucose PET/CT, transrectal real-time elastosonography (TRTE), and shear-wave elastosonography (SWE). The eligible studies were identified through systematical searching for the literature in electronic databases including PubMed, Cochrane, and Web of Science. On the basis of the fixed-effects model, the pooled sensitivity (SEN), specificity (SPE), and area under the receiver operating characteristics curve (AUC) were calculated to estimate the diagnostic accuracy of 11C-choline PET/CT, 11C-acetate PET/CT, 18F-fluorocholine (FCH) PET/CT, 18F-fluoroglucose (FDG) PET/CT, TRTE, and SWE. All the statistical analyses were conducted with R language Software. The present meta-analysis incorporating a total of 82 studies demonstrated that the pooled sensitivity of the six imaging techniques were sorted as follows: SWE > 18F-FCH PET/CT > 11C-choline PET/CT > TRTE > 11C-acetate PET/CT > 18F-FDG PET/CT; the pooled specificity were also compared: SWE > 18F-FCH PET/CT > 11C-choline PET/CT > TRTE > 18F-FDG PET/CT > 11C-acetate PET/CT; finally, the pooled diagnostic accuracy of the six imaging techniques based on AUC were ranked as below: SWE > 18F-FCH PET/CT > 11C-choline PET/CT > TRTE > 11C-acetate PET/CT > 18F-FDG PET/CT. SWE and 18F-FCH PET/CT imaging could offer more assistance in the early diagnosis of PCa than any other studied imaging techniques. However, the diagnostic ranking of the six imaging techniques might not be applicable to the clinical phase due to the shortage of stratified analysis.

Use of PET tracers for parathyroid localization: a systematic review and meta-analysis.

PURPOSE: The 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. METHODS: A study was considered eligible when the following criteria were met: (1) adults ≥17 years 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. RESULTS: Twenty-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. CONCLUSIONS: The 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.

Comparative effectiveness of [(18) F]-fluorocholine PET-CT and pelvic MRI with diffusion-weighted imaging for staging in patients with high-risk prostate cancer.

BACKGROUND: Accurate staging is important before surgical decision in patients with high-risk prostate cancer (PCa). The purpose of this study was to prospectively compare the diagnostic performance of (18) F-FCholine and MRI with diffusion weighted imaging (DWIMRI) for local and regional lymph node (LN) staging before radical prostatectomy (RP) with extended pelvic lymphadenectomy (PLND). METHODS: We identified 47 patients who underwent (18) F-FCholine and DWIMRI followed by surgical treatment (either prostatectomy or LN dissection or an association of prostatectomy and LN dissection) between May 2010 and December 2012 at Bordeaux University Hospital. These patients were part of a prospective study (EudraCT number 2009-014839-21) evaluating the interest of (18) F-FCholine in staging of high-risk PCa. Diagnostic performances were retrospectively determined for each of (18) F-FCholine and DWIMRI considering LN invasion, each of prostate sextants, capsular invasion and extension to seminal vesicles. (18) F-FCholine and MR findings were correlated with histological findings. RESULTS: In a region-based LN analysis, the sensitivity and positive predictive value specificity were respectively, 56% and 98% for (18) F-Choline, and 17% and 97% for DWIMRI. In a patient-based analysis the sensitivity and positive predictive value were respectively 78% and 94% for (18) F-Choline and 33% and 84% for DWIMRI (P = 0.015). For tumor staging, DWIMRI showed better performances with a better specificity (69%) for sextants analysis and sensitivity to detect seminal vesicle invasion (73% vs. 36%). CONCLUSIONS: (18) F-FCholine imaging appears to provide helpful additional information in the staging of high-risk PCa. It appears essential for predicting LN status due to its higher sensitivity and specificity for LN involvement. However, despite excellent performance, it cannot replace MRI that remains better for tumoral localization and local evaluation, especially for seminal vesicle invasion. PATIENT SUMMARY: This study highlights the interest of (18) F-Choline in the staging of high risk prostate cancer in addition with DWI MRI, especially so in the evaluation of lymph node involvement due to its high sensitivity and excellent specificity.

Optimal scan time for evaluation of parathyroid adenoma with [(18)F]-fluorocholine PET/CT.

BACKGROUND: Parathyroid adenomas, the most common cause of primary hyperparathyroidism, are benign tumours which autonomously produce and secrete parathyroid hormone. [(18)F]-fluorocholine (FCH), PET marker of cellular proliferation, was recently demonstrated to accumulate in lesions representing enlarged parathyroid tissue; however, the optimal time to perform FCH PET/CT after FCH administration is not known. The aim of this study was to determine the optimal scan time of FCH PET/CT in patients with primary hyperparathyroidism. PATIENTS AND METHODS: 43 patients with primary hyperparathyroidism were enrolled in this study. A triple-phase PET/CT imaging was performed five minutes, one and two hours after the administration of FCH. Regions of interest (ROI) were placed in lesions representing enlarged parathyroid tissue and thyroid tissue. Standardized uptake value (SUVmean), retention index and lesion contrast for parathyroid and thyroid tissue were calculated. RESULTS: Accumulation of FCH was higher in lesions representing enlarged parathyroid tissue in comparison to the thyroid tissue with significantly higher SUVmean in the second and in the third phase (p < 0.0001). Average retention index decreased significantly between the first and the second phase and increased significantly between the second and the third phase in lesions representing enlarged parathyroid tissue and decreased significantly over all three phases in thyroid tissue (p< 0.0001). The lesion contrast of lesions representing enlarged parathyroid tissue and thyroid tissue was significantly better in the second and the third phase compared to the first phase (p < 0.05). CONCLUSIONS: According to the results the optimal scan time of FCH PET/CT for localization of lesions representing enlarged parathyroid tissue is one hour after administration of the FCH.

Use of [18F]fluorocholine PET/CT in the detection of primary hyperparathyroidism in paediatrics: a case report.

OBJECTIVES: The most common cause of primary hyperparathyroidism (PPH) in children is a parathyroid adenoma. Among this population, PPH exhibits higher levels of morbidity, severity and target organ involvement compared to adults. When there is suspicion of PPH, cervical ultrasound and 99mTc-sestamibi SPECT/CT are the imaging test traditionally indicated. Among adults, the use of [18F]fluorocholine PET/CT has shown a higher sensitivity than ultrasound and [99mTc]sestamibi SPECT/CT, leading to an expanding adoption in recent years. However, its role in paediatrics has not been clearly defined yet. CASE PRESENTATION: The patient is an adolescent female aged 13 years presented with lithiasis. The analytical study revealed elevated PTH, hipovitaminosis D, hypercalcaemia and hypophosphataemia. Due to the suspicion of PPH, cervical ultrasound and 99mTc-sestamibi SPECT/C were performed, failing to identify hyperfunctioning parathyroid glands. We proceeded to carry out a [18F]fluorocholine PET/CT where a hypermetabolic nodular image was identified, compatible with a hyperfunctioning parathyroid adenoma. The patient underwent surgery, resulting in the normalisation of PTH levels. Pathological anatomy confirmed the presence of a parathyroid adenoma. CONCLUSIONS: In cases where conventional imaging tests yield negative results or discrepancies, we suggest the possibility of the use of [18F]fluorocholine PET/CT for the detection of hyperfunctioning parathyroid adenomas.

Odd Sites of Parathyroid Adenomas: 18F-fluorocholine PET/CT Pointing to the Right Place.

Primary hyperparathyroidism is mostly caused by parathyroid adenoma(s) which are generally localized using routine imaging modalities such as neck ultrasonography and 99mTc-SestaMIBI scintigraphy. However, these can miss ectopic parathyroid adenomas due to their limited sensitivities. These ectopic lesions can later lead to failure of surgical excision and necessitate the need for a re-exploration. 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) can help in the localization of these ectopic adenomas due to its superior detection rates and spatial resolution. Herein, we report a case of ectopic parathyroid adenomas that were localized on FCH PET/CT.