Search

Objective: Prospectively evaluate the impact of fluorodeoxyglucose-fluorine-18 positron emission tomography (FDG-PET) in the management of recurrence of advanced head and neck squamous cell carcinoma during the first year after treatment. Study Design: Seventy patients were followed-up every 6 to 8 weeks during the first year after initial combined curative therapy. FDG-PET, together with conventional imaging and endoscopy were performed systematically at 1 year (group A) or prompted earlier in case of clinically suspicious recurrence (group B). The referring physician evaluated the impact of FDG-PET on the patient's management. Another clinician checked the pertinence of decisions. Results: FDG-PET had a therapeutic impact in 8 of 43 group A patients and in 16 of 27 group B patients; the overall rate was 34%. This change was pertinent in 5 of 8 and 14 of 16 cases, respectively. Overall pertinence rate of decisions was 90% versus 70% without FDG-PET. Conclusions: FDG-PET had a significant overall therapeutic impact; the induced decisions were either pertinent or just led to "futile" noninvasive examinations. Systematic FDG-PET had a significantly lesser impact in comparison with FDG-PET motivated by clinical suspicion. [ABSTRACT FROM AUTHOR]

Presents guidelines of the organizing committee Standards, Options and Recommendations for the use of positron emission tomography with 2-[[sup]18F]fluoro-2-deoxy-D-glucose (FDP-PET scanning) in oncology. Definition of Standards, Options and Recommendations and level of evidence; Advantages of positron emission tomography; Availability of scientific data and the development of Standards, Options, and Recommendations for the role of and indications for FDG-PET scanning in oncology.

Introduction AMBA is a bombesin analogue that binds to GRPr. In a mouse model of estrogen-dependent human breast cancer, we tested whether 68 Ga-AMBA can be used for PET detection of GRPr-expressing tumors and could be more accurate than 18 F-FDG to monitor tumor response to hormone therapy. Methods The radiolabeling of 68 Ga-AMBA was automated using a R&D Synchrom module. ZR75-1, a breast cancer cell line, was xenografted in nude mice. 68 Ga-AMBA tumor uptake was compared with that of 18 F-FDG before and after treatment with tamoxifen. Results AMBA was 68 Ga-radiolabelled in 30 min with 95.3% yield and purity ≥ 98%. Prior to treatment, 68 Ga-AMBA was highly concentrated into tumors (tumor to non-tumor ratio = 2.4 vs. 1.3 with 18 F-FDG). With tamoxifen treatment (n = 6) 68 Ga-AMBA uptake plateaued after 1 week and decreased after 2 weeks, with a significant reduction compared to controls (n = 4). In contrast the effect of tamoxifen treatment could not be appreciated using 18 F-FDG. Conclusions 68 Ga-AMBA appeared better than 18 F-FDG to visualize and monitor the response to hormone treatment in this breast cancer model. [ABSTRACT FROM AUTHOR]

Precise anatomic localization of insulinomas is crucial for surgical treatment. Current routine noninvasive imaging techniques, including CT, MRI, and 68 Ga-DOTA-somatostatin analog (DOTA-SSA) PET/CT, have limited sensitivity. Endoscopic ultrasound is highly sensitive but invasive. In this prospective multicenter study, we compared the diagnostic accuracy of 68 Ga-NODAGA-exendin-4 (exendin) PET/CT with all routine imaging procedures for the localization of insulinomas. Methods: Sixty-nine adults with biochemically proven adult endogenous hyperinsulinemic hypoglycemia underwent exendin PET/CT and current routine imaging. Images were evaluated in a clinical reading and in an expert reading. Image quality was determined by quantitative analysis. Results: Based on clinical readings, the accuracy of exendin PET/CT (94.4%; 95% CI, 84.6%-98.8%) was greater than that of DOTA-SSA PET/CT (64.8%; 95% CI, 50.6%-77.3%), contrast-enhanced CT/contrast-enhanced diffusion-weighted imaging-MRI (83.3%; 95% CI, 70.7%-92.1%), and endoscopic ultrasound (82.8%; 95% CI, 64.1%-94.1%). In 13% of patients, a correct diagnosis was only reached after exendin PET/CT. Interobserver agreement between readings was higher for exendin PET/CT than for DOTA-SSA PET/CT and contrast-enhanced CT/contrast-enhanced diffusion-weighted imaging-MRI (Cohen κ, 1.0 vs. 0.5 and 0.55). Exendin PET/CT provided a higher insulinoma-to-background ratio (15.3 ± 6.7 vs. 5.2 ± 3.0) and contrast-to-noise ratio (22.6 ± 11.1 vs. 5.1 ± 3.7) than did DOTA-SSA PET/CT. Conclusion: This study demonstrates the superiority of exendin PET/CT in a unique prospective comparison to all current routine imaging modalities for preoperative localization of benign insulinomas, providing the level of evidence needed for clinical implementation., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

In patients with confirmed hyperparathyroidism (HPT) scheduled for surgical treatment, the preoperatory imaging permits to optimize the operatory protocol of parathyroidectomy (PTX), in particular by selecting those patients who can benefit from minimally invasive PTX (MIPTX). The MIPTX has the merit to shorten the operative time, incision length, and to reduce the operatory risks. With preoperative localization studies, the rate of PTX failure, in particular due to nonsuspected multiglandular or ectopic disease, has been profoundly decreased. The first cases of incidental localization of abnormal parathyroid glands (PTs) on FCH PET/CTs performed for another indication were reported more than one decade ago. Since then, significant amount of data from heterogeneous series of patients consistently confirmed better diagnostic performances of FCH PET/CT (sensitivity for detection of abnormal PT 97%, range 96%-98%) in comparison with other radiopharmaceuticals, ultrasonography or 4D-CeCT in localizing hyperfunctioning parathyroid glands (HFPTGs) in case of primary HPT. Utility of FCH PET/CT in case of renal HPT has been reported in fewer series. The article discusses and summarizes the bibliographic evidence on documented indications of FCH PET/CT in patients with HPT, its safety profile, the practice of FCH PET/CT and interpretation of FCH PET/CT findings, including potential interpretation pitfalls and tips to avoid them. Our real-world experience over 12 years reinforces published evidence supporting the use of FCH PET/CT as the first-line radionuclide imaging technique in patients with all types of HPT in whom surgery is an option., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context: Primary hyperparathyroidism (PHPT) is commonly diagnosed in the setting of hypercalcemia, whereas normocalcemic primary hyperparathyroidism (NHPT) may be misdiagnosed., Objective: Our objective was to compare patients with hypercalcemic hyperparathyroidism (HPHPT) vs patients with NHPT hypercalciuric renal stones., Methods: We took advantage of a routine calcium load test performed in patients with hypercalciuric renal stones to assess retrospectively among patients with PHPT the prevalence and characteristics of NHPT and HPHPT under a calcium-restricted diet., Results: Among 1671 patients with hypercalciuria, 91 patients had a final diagnosis of PHPT (postload ionized calcium [iCa] > 1.31 mmol/L and parathyroid hormone [PTH] > 30 pg/mL). Prevalence of NHPT is 40% of all PHPT; however, according to total serum calcium, 4/35 NHPT and 7/56 HPHPT cases would have been misclassified in the other group. Eighteen of 35 NHPT and 40/56 HPHPT cases underwent parathyroidectomy. No significant characteristics relating to parathyroid weight, stone composition, or bone remodeling biomarkers were detected between groups. Although iCa is higher in HPHPT in the fasting state and after calcium load, we found no difference for calcium diet, 24-hour calciuria, or calcitriol. Renal calcium excretion postload increased by 303% in NHPT but only 176% in HPHPT (P = .01) likely explained by a lesser PTH decrease (P = .02). However, a strong negative association (P < .0001) detected between pooled preload and postload iCa and PTH only in the NHPT group suggests a persistent efficient PTH-CaSR control within the parathyroid glands in this group., Conclusion: Our data show the relevance of dynamic tests to unmask NHPT in patients with hypercalciuric renal stones., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Abstract: Nonrecurrent inferior laryngeal nerve (NRILN) is a rare anatomical variant, which significantly increases the risk of nerve injury during neck surgery, for example, thyroidectomy or parathyroidectomy (PTX). The absence of the brachiocephalic trunk and presence of arteria lusoria (AL) are strong predictors of NRILN in the right neck. FCH PET/CT is now a recognized imaging modality in hyperparathyroidism (HPT). We report 2 patients with primary or renal HPT in whom FCH PET detected right HFPTs and low-dose noncontrast CT evidenced AL. The NRILN was thus preserved during PTX. We recommend searching for AL on FCH PET/CT (even low-dose) in HPT before PTX., Competing Interests: Conflicts of interests and sources of funding: none declared., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: c-MET is a transmembrane receptor involved in many biological processes and contributes to cell proliferation and migration during cancer invasion process. Its expression is measured by immunehistochemistry on tissue biopsy in clinic, although this technique has its limitations. PET-CT could allow in vivo mapping of lesions expressing c-MET, providing whole-body detection. A number of radiopharmaceuticals are under development for this purpose but are not yet in routine clinical use. EMP100 is a cyclic oligopeptide bound to a DOTA chelator, with nanomolar affinity for c-MET. The aim of this project was to develop an automated method for radiolabelling the radiopharmaceutical [ 68 Ga]Ga-EMP100., Results: The main results showed an optimal pH range between 3.25 and 3.75 for the complexation reaction and a stabilisation of the temperature at 90 °C, resulting in an almost complete incorporation of gallium-68 after 10 min of heating. In these experiments, 90 µg of EMP-100 peptide were initially used and then lower amounts (30, 50, 75 µg) were explored to determine the minimum required for sufficient synthesis yield. Radiolysis impurities were identified by radio-HPLC and ascorbic acid and ethanol were used to improve the purity of the compound. Three batches of [ 68 Ga]Ga-EMP100 were then prepared according to the optimised parameters and all met the established specifications. Finally, the stability of [ 68 Ga]Ga-EMP100 was assessed at room temperature over 3 h with satisfactory results in terms of appearance, pH, radiochemical purity and sterility., Conclusions: For the automated synthesis of [ 68 Ga]Ga-EMP100, the parameters of pH, temperature, precursor peptide content and the use of adjuvants for impurity management were efficiently optimised, resulting in the production of three compliant and stable batches according to the principles of good manufacturing practice. [ 68 Ga]Ga-EMP100 was successfully synthesised and is now available for clinical development in PET-CT imaging., (© 2023. Springer Nature Switzerland AG.)

Breast cancer remains the most common cause of cancer death among women. Despite its considerable histological and molecular heterogeneity, those characteristics are not distinguished in most definitions of oligometastatic disease and clinical trials of oligometastatic breast cancer. After an exhaustive review of the literature covering all aspects of oligometastatic breast cancer, 35 experts from the European Organisation for Research and Treatment of Cancer Imaging and Breast Cancer Groups elaborated a Delphi questionnaire aimed at offering consensus recommendations, including oligometastatic breast cancer definition, optimal diagnostic pathways, and clinical trials required to evaluate the effect of diagnostic imaging strategies and metastasis-directed therapies. The main recommendations are the introduction of modern imaging methods in metastatic screening for an earlier diagnosis of oligometastatic breast cancer and the development of prospective trials also considering the histological and molecular complexity of breast cancer. Strategies for the randomisation of imaging methods and therapeutic approaches in different subsets of patients are also addressed., Competing Interests: Declaration of interests DEO-L reports honoraria from BMUC and unrestricted grants from Janssen for consensus nuclear medicine meetings in 2020 and 2022, outside the submitted work. LF reports grants from Bristol Myers Squibb and Banque Publique d’Investissement; honoraria for lectures from GE Healthcare, Fujifilm, and Median Technologies; support for attending meetings from Guerbet; participation on a safety monitoring board with Pandas Prodige; and research collaborations with Philips, Ariana Pharma, Evolucare, and Dassault Systems, outside the submitted work. EL reports royalties or licences from Springer, outside the submitted work. DK reports grants from Merck and honoraria from Merck Sharp & Dohme and Pfizer, outside the submitted work. SK reports an advisory role and study material from Novartis, Amgen, Somatex, Daiichi Sankyo, Gilead, AstraZeneca, Pfizer, Eli Lilly, MSD, and Roche for the submitted work; consulting fees from Eli Lilly and MSD; honoraria from AstraZeneca, Eli Lilly, and Pfizer; support for attending meetings from Roche, Daiichi Sankyo, and Eli Lilly; participation on boards with Novartis, Amgen, Somatex, pfm medical, MSD, Daiichi Sankyo, Seagen, Gilead Science, Agendia, Exact Science, Roche, Sonoscape, Eli Lilly, AstraZeneca, and Pfizer; and leadership in other boards with AGO, WSG, and ESMO, outside the submitted work. IM reports honoraria supported by Eli Lilly, Novartis, Pfizer, Seagen, Gilead, and Accuray, outside the submitted work. WMHO reports grants from Pfizer and AstraZeneca, travel grants from Daiitchi, and participation on an advisory board with GE, outside the submitted work. KH reports personal fees from Bayer, Sofie Biosciences, SIRTEX, Adacap, Curium, Endocyte, IPSEN, Siemens Healthineers, GE Healthcare, Amgen, Novartis, Y-mAbs, Aktis Oncology, Theragnostics, Pharma15, Debiopharm, AstraZeneca, and Janssen; non-financial support from ABX; and grants and personal fees from BTG, outside the submitted work. FC reports honoraria from Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, Gilead, GlaxoSmithKline, Iqvia, Macrogenics, Medscape, Merck Sharp, Meus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, priME Oncoloy, Roche, Sanofi, Samsung Bioepis, Seagen, Teva, and Touchime, and support for attending meetings from Pfizer and Roche, outside the submitted work. BL reports participation on boards for AstraZeneca, Pfizer, Eli Lilly, Daiichi-Sankyo, Novartis, Pierre Fabre, Breast International Group Executive Committee, EORTC Breast Cancer Group, and Swedish Association of Breast Oncologists, outside the submitted work. WK reports consulting fees from Mint Medical and honoraria from Bristol Myers Squibb, outside the submitted work. CD reports consulting fees from Terumo, Sitex, and PSI CRO; honoraria from Ipsen; and a chairing role for EORTC Imaging Group, outside the submitted work. ES reports royalties from Springer; honoraria from Cancerodigest, Curio Science, Egis, Eli Lilly, Exact Sciences, Gilead, high5md, MSD, Novartis, and Pfizer; support for attending meetings from Egis, Gilead, Novartis, Pfizer, and Roche; participation on boards with AstraZeneca, Eli Lilly, Exact Sciences, Novartis, Oncompass Medicine, and Stowarzyszenie Rozowy Motyl; stock options from AstraZeneca, Eli Lilly, and Pfizer; receipt of equipment from AstraZeneca and Eli Lilly; and interests with Amgen, AstraZeneca, Eli Lilly, Novartis, OBI Pharma, Pfizer, Roche, and Samsung, outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: During the past decade, 18 F-fluorocholine (FCH) PET/CT has been continuously performed at Tenon Hospital (Paris, France) for the detection of hyperfunctioning parathyroid glands (PT)., Methods: A cohort of 401 patients, deliberately referred for HPT since September 2012, has been analyzed. The aim of this real-life retrospective study was to determine the diagnostic utility of FCH in this setting, overall and in subgroups according to the type of hyperparathyroidism (HPT), the context of FCH in the imaging work-up and in the patient's history: initial imaging or persistence or recurrence after previous parathyroidectomy (PTX). The influence of the histologic type of resected PTs, hyperplasia or adenoma, on the preoperatory detection on FCH PET/CT has been studied as well., Results: Four hundred one FCH PET/CTs were included in the cohort, performed in 323 patients with primary HPT (pHPT), including 18 with familial HPT (fHPT), and in 78 patients with secondary renal HPT (rHPT). The overall positivity rate in the 401 FCH PET/CTs was 73%. The PTX rate was twice greater in patients whose FCH PET/CT was positive than negative (73% vs. 35%). Abnormal PT(s) were pathology proven in 214 patients: only hyperplastic gland(s) in 75 cases and at least one adenoma in 136 cases; FCH PET/CT sensitivity was 89% and 92%, respectively. Similarly, there was no significant difference in patient-based sensitivity whether FCH PET/CT was performed as 1 st line or later in the imaging work-up, or indicated for initial imaging or for suspicion of persistent or recurrent HPT. Gland-based sensitivity was significantly lower for hyperplasia than for adenoma (72% and 86%, respectively). The lowest gland-based sensitivity value was 65%, observed in case of hyperplasia and when FCH was performed late in the imaging work-up. FCH PET/CT correctly showed multiglandular HPT (MGD) in 36/61 proven cases, 59%. Results of ultrasonography (US) and 99m Tc-sestaMIBI (MIBI) imaging were available in 346 and 178 patients, respectively. For both modalities, the corresponding sensitivity values were significantly less than those of FCH PET/CT (e.g., overall gland-based sensitivity 78% for FCH, 45% for US, 30% for MIBI) and MGD was detected in 32% of cases by US and 15% by MIBI., Conclusions: Although FCH PET/CT has been performed since 2017 as 1 st line imaging for HPT at Tenon Hospital (Paris, France), a large majority of patients underwent prior US and/or MIBI in their preoperative work-up. Therefore, a selection bias is very likely, as most patients referred to FCH PET/CT had non-conclusive or discordant results of US and MIBI, explaining the low performance of those modalities in the present cohort compared to published results. Nevertheless, the superiority of FCH PET/CT over US and MIBI in detecting abnormal PTs reported in various comparative studies is definitely confirmed in this larger real-life cohort. The detection with FCH PET/CT of hyperplastic PTs was somewhat lower than that of adenomas but was better than using US or MIBI. The present results lead to recommend FCH PET/CT as the first line imaging modality in HPT when it is widely available or, if less available, at least in HPT with predominance of hyperplasia and/or MGD.

Parathyroid imaging is essential for the detection and localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism (pHPT). Surgical treatment of pHPT mainly consists of minimally invasive parathyroidectomy (MIP), as a single adenoma represents the most common cause of this endocrine disorder. Successful surgery requires an experienced surgeon and relies on the correct preoperative detection and localization of hyperfunctioning parathyroid glands. Failure to preoperatively identify the culprit parathyroid gland by imaging may entail a more invasive surgical approach, including bilateral open neck exploration, with higher morbidity compared to minimally invasive parathyroidectomy. Parathyroid imaging may be also useful before surgery in case of secondary hyperparathyroidism (sHPT) or hereditary disorders (MEN 1, 2, 4) as it enables correct localization of typically located parathyroid glands, detection of ectopic as well as supernumerary glands. It is now accepted by most surgeons experienced in parathyroid surgery that preoperative imaging plays a key role in their patients' management. Recently, the European Association of Nuclear Medicine (EANM) issued an updated version of its Guidelines on parathyroid imaging. Its aim is to precise the role and the advantages and drawbacks of the various imaging modalities proposed or well established in the preoperative imaging strategy. It also aims to favor high performance in indicating, performing, and interpreting those examinations. The objective of the present article is to offer a summary of those recent EANM Guidelines and their originality among other Guidelines in this domain issued by societies of nuclear medicine physicians or other disciplines.

18 F-fluorocholine (FCH) PET/CT is now well established to detect the hyperfunctioning parathyroid glands (HFPTG) in a case of sporadic primary hyperparathyroidism (pHPT), but only limited evidence is available about the utility of FCH PET/CT to detect the HFPTG in patients with multiple endocrine neoplasia (MEN) type 1 or 4. The pHPT in this context frequently consists in a multiglandular disease with small hyperplastic glands rather than adenomas, which is challenging for imaging modalities. The data of patients with MEN1 or MEN4 after parathyroidectomy referred to FCH PET/CT for presurgical localization of HFPTG were retrospectively reviewed, including follow-up after parathyroidectomy, in search for diagnostic performance and for potential pitfalls. In the present cohort, 16 patients referred to FCH PET/CT as part of their initial pHPT work-up were subsequently operated, 44 abnormal parathyroid glands (PT) were resected, of which 32 (73%) had been detected on FCH PET/CT and 2 considered as equivocal foci. Nine patients referred to FCH PET/CT for recurrent pHPT who were subsequently operated, 14 abnormal PT were resected, all had been detected on FCH PET/CT. FCH PET/CT permitted a unilateral approach for PTx in 4 of them. In one patient with MEN4 and pHPT, the HFPTG could not be visualized on FCH PET/CT but was localized by ultrasonography. Several causes of false positive or false negative results, incidental finding and pitfalls are listed and discussed. FCH PET/CT has a positive benefit/risk ratio in the detection of HFPTG in case of MEN1 (the data in MEN4 being currently very limited) with the most effective detection rate of current imaging modalities for HFPTG, few pitfalls, and an adequate impact on patient management compared to sesta MIBI SPECT and ultrasonography.

Introduction: Endometriosis is a common gynecologic condition that may be visualized on 18F-FDG PET/CT and mimic lesions of malignancy. We analyzed the interference of known or suspected endometriosis in reporting 18F-FDG PET/CT performed in another indication., Results: The PET/CT images of 18 women with known (n = 15) or suspected (n = 3) endometriosis were analyzed. Based on clinical follow-up and results of other imaging, biopsy, and/or postsurgical histology, the presence of lesions of endometriosis at the time of 18F-FDG PET/CT was confirmed in 13 of 18 patients (72%). The per-patient positivity rate of 18F-FDG PET/CT was 8/18 (44%; 95% confidence interval, 22%-69%). The patient-based detection rate of 18F-FDG PET/CT in patients with confirmed lesions of endometriosis was 8/13 (62%; confidence interval, 32%-86%). On per-lesion/site basis, 18F-FDG PET/CT detected 11 of 20 sites (55%) of endometriosis. The SUVmax of these lesions/sites ranged between 1.8 and 5.3 (median, 3.8). In 9 of 18 patients (50%), a total of 13 non-endometriosis-related lesions/sites were detected by 18F-FDG PET/CT; their SUVmax ranged between 2.7 and 23 (median, 9.4)., Conclusion: The interference of known or suspected endometriosis in reporting 18F-FDG PET/CT performed in another indication was limited but possible and should be kept in mind, even in postmenopausal women, as the oldest patient with 18F-FDG-positive endometriosis was aged 63 years. The lesions of endometriosis showed inconstant 18F-FDG uptake with overlap of SUVmax with low-grade malignancies. In our series, the greatest SUVmax value of lesion of endometriosis was 5.3, somewhat higher than the threshold of 4 previously proposed for identification of malignant transformation of endometriosis., Competing Interests: Conflicts of interest and sources of funding: Supported by grant: KEGA 058UK-4/2020., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Despite growing evidence of a superior diagnostic performance of 68 Ga-PSMA-11 over 18 F-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 68 Ga-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.

Introduction: Nuclear medicine parathyroid imaging is important in the identification of hyperfunctioning parathyroid glands in primary hyperparathyroidism (pHPT), but it may be also valuable before surgical treatment in secondary hyperparathyroidism (sHPT). Parathyroid radionuclide imaging with scintigraphy or positron emission tomography (PET) is a highly sensitive procedure for the assessment of the presence and number of hyperfunctioning parathyroid glands, located either at typical sites or ectopically. The treatment of pHPT is mostly directed toward minimally invasive parathyroidectomy, especially in cases with a single adenoma. In experienced hands, successful surgery depends mainly on the exact preoperative localization of one or more hyperfunctioning parathyroid adenomas. Failure to preoperatively identify the hyperfunctioning parathyroid gland challenges minimally invasive parathyroidectomy and might require bilateral open neck exploration., Methods: Over a decade has now passed since the European Association of Nuclear Medicine (EANM) issued the first edition of the guideline on parathyroid imaging, and a number of new insights and techniques have been developed since. The aim of the present document is to provide state-of-the-art guidelines for nuclear medicine physicians performing parathyroid scintigraphy, single-photon emission computed tomography/computed tomography (SPECT/CT), positron emission tomography/computed tomography (PET/CT), and positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with pHPT, as well as in those with sHPT., Conclusion: These guidelines are written and authorized by the EANM to promote optimal parathyroid imaging. They will assist nuclear medicine physicians in the detection and correct localization of hyperfunctioning parathyroid lesions.

Rationale: Peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE (oxodotreotide) results in external radiation exposure from the patient. In the PREELU observational prospective study, we determined the equivalent dose rate at 1 m of the patient (EDR-1m) for a period following PRRT. The main objective was to predict which patients could be discharged from the hospital at approximately 3 h after the administration of 177 Lu-DOTATATE, i.e. at the end of the infusion of amino-acids according to our PRRT protocol. As presenting no undue risk of radiation exposure for the public, those patients could be treated as outpatients or day patients, rather than inpatients. Methods: We sequentially measured EDR-1m facing the sternum and then the pelvis during 50 PRRT in 24 patients with metastatic neuroendocrine tumours, each 30 minutes after ending administration of Lutathera, over at least 180 minutes. Results: 180 minutes after the administration of ca. 7400 MBq of Lutathera, EDR-1m was <40 µSv/h in all cases, and <25 µSv/h in 32 cases (64%). After an overnight hospital stay, EDR-1m was <25 µSv/h in all cases. The EDR-1m value measured facing the sternum was the greatest in about one-fourth of paired measurements. In patients whose creatinine clearance was >96 mL/min/1.73m 2 , the EDR-1m was most likely (predictive value=90%) to drop below 25 µSv/h within 180 minutes after the administration of Lutathera. In 16 patients who benefited from several PRRT cycles, the creatinine clearance did not decrease significantly from one cycle to the next, probably due to the kidney protection by the amino-acid infusion. The patients whose EDR-1m dropped below 25 µSv/h at 180 minutes during their first PRRT cycle were unlikely (predictive value= 88%) to decease during the following two years. Conclusion: All patients could have been discharged 3 h after administration according to the criterion EDR-1m <40 µSv/h. Using EDR-1m <25 µSv/h as criterion, an extended hospital stay beyond 3 h would have been necessary in around one-third of the PRRT treatments and could be anticipated based on creatinine clearance ≤96 mL/min/1.73m 2 . EDR-1m <25 µSv/h at 180 min during the first PRRT yielded a strong predictive value on the patient's survival at two years, a finding that should be confirmed in future studies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: Research and scholarship are core elements of the academic mission. Yet fulfilling institutional and accreditation requirements for scholarly activity can be challenging, particularly for teaching-intensive institutions. This paper describes strategies for employing a teacher-scholar model to stimulate and sustain scholarly activity., Methods: Metrics of scholarly productivity were programmatically assessed and reported for at least five years following implementation of sixteen different strategic initiatives at three teaching-intensive colleges of pharmacy. Data reported included publications (original peer-reviewed publications, case reports, review articles), presentations (posters, podiums, and continuing education sessions), peer-reviewed published abstracts, grants awarded, and total extramural funding per annum. Faculty and student engagement in scholarship was indicated by authorship on at least one scholarly work., Results: Broad increases in metrics of scholarly productivity were observed, while the timing and degree of change varied (1.4-fold to 10.4-fold, across all institutions, all years). Notably, the most robust growth was observed in grantsmanship and the number of faculty and student contributors to scholarly works. A key observation was that increased scholarly output was sustained, as during the most recent three-year period publications increased 1.6-fold, grants and extramural funding increased 3.4- and 15.8-fold, respectively, and faculty and student contributors increased 1.8- and 4.5-fold, respectively., Conclusions: Overall, these data point to a substantive, detailed approach for increasing scholarship at diverse, teaching-intensive institutions by implementing cost-conscious strategies, including clear ties between scholarly effort/productivity and faculty performance/advancement, strong faculty development and mentoring, institutional commitments to infrastructure and research budgets, and student engagement in scholarly activities., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To examine the financial impact of automatic formulary substitution of nebulization solutions for pressurized metered dose inhalers and dry powder inhalers and the effect of the automatic substitution initiative on respiratory care practitioner (RCP) workload at a community hospital., Methods: A retrospective observational study was conducted in a 326-bed nonacademic community hospital. Adult patients who received respiratory medications and had an inpatient stay, were admitted for observation, or had an emergency room visit from December 2016 through February 2017 (the control group) or from December 2017 through February 2018 (the study group) were included in the analysis. The primary outcomes were the cost of respiratory medications per hospital stay and the number of RCP visits per hospital stay. The secondary outcome was the cost of wasted doses per hospital stay., Results: A total of 3,766 patients were included in the study: 2,030 in the study group and 1,736 in the control group. The mean cost of respiratory medications per hospital stay was significantly lower in the study group vs the control group ($13.29 vs $36.48, P < 0.001). The mean number of RCP visits per hospital stay was also statistically lower in the study group vs the control group (11.6 vs 12.9, P = 0.04). The mean cost of wasted doses was significantly lower in study group vs the control group ($0.25 vs $22.91, P < 0.001)., Conclusion: Automatic formulary substitution of nebulization solutions for inhaler medications significantly decreased medication costs without increasing the average number of RCP visits per hospital stay., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A man experienced pain in the right hemithorax 6 months after a first-line therapy for multiple myeloma (MM). FDG PET/CT showed a large extramedullary extent in the right hemithorax, which was biopsy proven. During the second-line treatment, FDG PET/CT showed no response as well as a suspected myocardium spread, a rare extramedullary location in MM. F-Fluorocholine PET/CT and then MRI confirmed myocardium lesions. This case confirms that F-fluorocholine PET/CT is able to detect MM recurrence and may be used to complete FDG PET/CT in difficult cases such as suspicion of cardiac MM.

Background: Primary hyperparathyroidism (HPT1) is the most frequent endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Its surgical management is challenging. We aimed to describe and compare the imaging findings of parathyroid ultrasound (US), sestaMIBI scintigraphy (sestaMIBI), and 18 F-fluorocholine (FCH) PET/CT in a series of MEN1 patients with HPT1., Methods: Retrospective analysis of a cohort of MEN1 patients with HPT1 assessed by parathyroid US, sestaMIBI scintigraphy and SPECT/CT, and FCH-PET/CT for potential surgery between 2015 and 2019., Results: Twenty-two patients with a confirmed diagnosis of MEN1 who presented with HPT1 and were assessed by the 3 imaging modalities were included. After imaging workups, 11 patients were operated on for the first time, 4 underwent a redo surgery, and 7 did not undergo an operation. The overall patient-based positivity rate of imaging was 91% (20 of 22) for parathyroid US and 96% (21 of 22) for both sestaMIBI and FCH-PET/CT. The 3 imaging modalities demonstrated negative findings in 1/22 patient who did not undergo surgery. Overall, 3 pathologic glands were not detected by any imaging technique. SestaMIBI and FCH-PET/CT both resulted in the same 3 false-positive results in ectopic areas with a significant uptake on two thymic carcinoid tumors and one inflammatory lymph node. FCH-PET/CT provided more surgically relevant data than sestaMIBI in 4/11 patients with initial surgery and in 1/4 patient who underwent redo surgery., Conclusions: Compared to sestaMIBI scintigraphy, FCH-PET/CT provides additional information regarding the number of pathologic parathyroid glands and their localization in MEN1 patients with HPT1.

A 47-year-old woman with a history of surgically treated abdominal paraganglioma and left thigh melanoma underwent an F-FDOPA PET/CT for suspected locoregional recurrence of paraganglioma. F-FDOPA PET/CT disconfirmed this recurrence but revealed 2 FDOPA-avid left inguinal lymph nodes, confirmed on a subsequent F-FDG PET/CT. Excision and pathology characterized these lymph nodes as melanoma metastases. F-FDOPA PET/CT is a widely used and valuable tool in the assessment of paraganglioma, both for staging and recurrence detection. Uptake of FDOPA has only rarely been documented in metastatic melanoma that could be a pitfall for detecting neuroendocrine tumors.

Introduction: Peptide-based imaging agents targeting prostate-specific membrane antigen (PSMA) have revolutionized the evaluation of biochemical recurrence of prostate cancer (PCa) but lacks sensitivity at very low serum prostate specific antigen (PSA) levels. Once recurrence is suspected, other positron emission tomography (PET) radiotracers could be of interest to discriminate between local and distant relapse. We studied [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) targeting glucose metabolism, [ 18 F]fluorocholine ([ 18 F]FCH) targeting membrane metabolism and peptide-based imaging agents [ 68 Ga]Ga-PSMA-11, [ 68 Ga]Ga-AMBA, [ 68 Ga]Ga-NODAGA-RGD and [ 68 Ga]Ga-DOTA-NT-20.3 targeting PSMA, gastrin releasing peptide receptor (GRPr), αvβ3 integrin and neurotensin type 1 receptor (NTSR1) respectively, in different PCa tumour models., Methods: Mice were xenografted with 22Rv1, an androgen-receptor (AR)-positive, PCa cell line that expresses PSMA and PC3, an AR-negative one that does not express PSMA. PET imaging using the different radiotracers was performed sequentially and the uptake characteristics compared to one other. NTSR1 and PSMA expression levels were analysed in tumours by immunohistochemistry., Results: [ 18 F]FDG displayed low but sufficient uptake to visualize PC3 and 22Rv1 derived tumours. We also observed a low efficacy of [ 18 F]FCH PET imaging and a low [ 68 Ga]Ga-NODAGA-RGD tumour uptake in those tumours. As expected, an elevated tumour uptake was obtained for [ 68 Ga]Ga-PSMA-11 in 22Rv1 derived tumour although no uptake was measured in the androgen independent cell line PC3, derived from a bone metastasis of a high-grade PCa. Moreover, in PC3 cell line, we obtained good tumour uptake, high tumour-to-background contrast using [ 68 Ga]Ga-AMBA and [ 68 Ga]Ga-DOTA-NT-20.3. Immunohistochemistry analysis confirmed high NTSR1 expression in PC3 derived tumours and conversely high PSMA expression in 22Rv1 derived tumours., Conclusion: PET imaging using [ 68 Ga]Ga-AMBA and [ 68 Ga]Ga-DOTA-NT-20.3 demonstrates that GRPr and NTSR1 could represent viable alternative targets for diagnostic or therapeutic applications in PCa with limited PSMA expression levels. More preclinical and clinical studies will follow to explore this potential., Advances in Knowledge and Implications for Patient: Peptide-based imaging agents targeting PSMA represent a major progress in the evaluation of biochemical recurrence of PCa but sometimes yield false negative results in some lesions. Continuing efforts have thus been made to evaluate other radiotracers. Our preclinical results suggest that [ 68 Ga]labelled bombesin and neurotensin analogues could serve as alternative PET radiopharmaceuticals for diagnostic or therapy in cases of PSMA-negative PCa., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study reports a relationship between Akt3 expression and tissue-specific regulation of the pI3K/Akt/mTOR signaling pathway by copaiba essential oil. Akt3, a protein kinase B isoform important for the regulation of neuronal development, exhibited differential expression levels in cells of various origins. In neuronal and microglial cells, where Akt3 is present, copaiba essential oil positively regulated the pI3K/Akt/mTOR signaling pathway. In contrast, in liver cells and T lymphocytes, where Akt3 is absent, copaiba essential oil negatively regulated the pI3K/Akt/mTOR signaling pathway. The expression of Akt3 via plasmid DNA in liver cells led to positive regulatory effects by copaiba essential oil on the pI3K/Akt/mTOR signaling pathway. In contrast, inhibition of Akt3 expression in neuronal cells via small interfering RNA molecules targeting Akt3 transcripts abrogated the regulatory effects of copaiba essential oil on the pI3K/Akt/mTOR signaling pathway. Interestingly, Akt3 expression did not impact the regulatory effects of copaiba essential oil on other signaling pathways. For example, copaiba essential oil consistently upregulated the MAPK and JAK/STAT signaling pathways in all evaluated cell types, independent of the Akt3 expression level. Collectively, the data indicated that Akt3 expression was required for the positive regulatory effects of copaiba essential oil, specifically on the pI3K/Akt/mTOR signaling pathway.

This study examined the biological activities of copaiba essential oil via measurement of its effects on signaling pathways in the SH-SY5Y neuronal cell line. Nanofluidic proteomic technologies were deployed to measure the phosphorylation of biomarker proteins within the signaling cascades. Interestingly, copaiba essential oil upregulated the pI3K/Akt/mTOR, MAPK, and JAK/STAT signaling pathways in neuronal cells. The effects of copaiba essential oil peaked at 30 min post-treatment, with a half-maximal effective concentration (EC 50 ) of approximately 80 ng/mL. Treatment with cannabinoid receptor 2 (CB2) agonist AM1241 or the inverse agonist BML190 abrogated the regulatory effects of copaiba essential oil on the pI3K/Akt/mTOR signaling pathway. Surprisingly, copaiba essential oil also activated the apoptosis signaling pathway and reduced the viability of SH-SY5Y cells with an EC 50 of approximately 400 ng/mL. Furthermore, β-caryophyllene, a principal constituent of copaiba essential oil, downregulated the pI3K/Akt/mTOR signaling pathway. Taken together, the findings indicated that copaiba essential oil upregulated signaling pathways associated with cell metabolism, growth, immunity, and apoptosis. The biological activities of copaiba essential oil were determined to be fast acting, CB2 mediated, and dependent on multiple chemical constituents of the oil. Nanofluidic proteomics provided a powerful means to assess the biological activities of copaiba essential oil., Competing Interests: C.B., M.W. and D.K.H. are employees of dōTERRA International, a company that produces and sells essential oils. D.K.H. and C.B. participated in the initial conceptualization of the project. C.B. and M.W. analyzed the chemical composition of copaiba essential oil using a GC–MS method with good laboratory practice (GLP) compliance.

Background: The diagnostic performance of 18 F-sodium fluoride positron emission tomography/computed tomography (PET/CT) (NaF), 18 F-fluorocholine PET/CT (FCH) and diffusion-weighted whole-body magnetic resonance imaging (DW-MRI) in detecting bone metastases in prostate cancer (PCa) patients with first biochemical recurrence (BCR) has already been published, but their cost-effectiveness in this indication have never been compared., Methods: We performed trial-based and model-based economic evaluations. In the trial, PCa patients with first BCR after previous definitive treatment were prospectively included. Imaging readings were performed both on-site by local specialists and centrally by experts. The economic evaluation extrapolated the diagnostic performances of the imaging techniques using a combination of a decision tree and Markov model based on the natural history of PCa. The health states were non-metastatic and metastatic BCR, non-metastatic and metastatic castration-resistant prostate cancer and death. The state-transition probabilities and utilities associated with each health state were derived from the literature. Real costs were extracted from the National Cost Study of hospital costs and the social health insurance cost schedule., Results: There was no significant difference in diagnostic performance among the 3 imaging modalities in detecting bone metastases. FCH was the most cost-effective imaging modality above a threshold incremental cost-effectiveness ratio of 3000€/QALY when imaging was interpreted by local specialists and 9000€/QALY when imaging was interpreted by experts., Conclusions: FCH had a better incremental effect on QALY, independent of imaging reading and should be preferred for detecting bone metastases in patients with biochemical recurrence of prostate cancer., Trial Registration: NCT01501630. Registered 29 December 2011.

Purpose: Paraneoplastic Cushing's syndrome (PCS) is frequently caused by neuroendocrine tumours (NETs). Approximately 20% of tumours are still occult years later. Gallium-68 somatostatin receptor-PET/CT is promising for the detection of the causal primary NET, but its role in case of recurrent PCS is rarely reported. We report our experience with DOTATOC PET/CT in localising the causal NET in cases of initial but also recurrent PCS, and its clinical impact., Methods: A retrospective review of all DOTATOC PET/CTs performed in consecutive patients referred for PCS to our centre, between January 2011 and June 2017, was done. Nineteen patients underwent 26 PET/CTs, 13 for detection of a primary NET, seven for persistent or recurrent PCS after resection, and six for surveillance after resection of NETs previously detected on a DOTATOC PET/CT in our centre., Results: Among the 13 PET/CTs performed to search for primary NET, five were positive: four carcinoid lung tumours were confirmed after resection and one lung focus was not confirmed since surgery would have carried a high risk. Clinical impact was 23% (3/13). Among the seven PET/CTs performed for persistent or recurrent PCS, six were true-positive, with confirmation of metastatic lymph nodes after resection. Clinical impact was 57% (4/7). All PET/CTs performed for surveillance were true-negative., Conclusions: DOTATOC PET/CT seems to be a valuable tool for detection of the NET responsible for persistent or recurrent PCS after surgery. In this context, DOTATOC PET/CT was more effective than for the detection of the causal tumour in initial PCS.

We aimed to evaluate the impact of prostate-specific membrane antigen ligand labelled with gallium-68 (PSMA-11) PET/CT in restaging patients with castration-resistant nonmetastatic prostate cancer (PCa). Thirty patients were included. At least one malignant focus was found in 27/30 patients (90%). The PSMA-11 PET/CT positivity rate in patients whose prostate-specific antigen serum level (PSA) was greater than 2 ng/ml was 100% (20/20), significantly superior to that of patients whose PSA was less than 2 ng/ml (7/10 = 70%). Six patients (20%) were categorized as oligometastatic (≤3 metastatic foci). Based on the 17 patients for whom a standard of truth was feasible, the overall sensitivity and specificity of PSMA-11 PET/CT in detecting residual disease in castration-resistant PCa patients were 87% and 100% respectively. PSMA-11 PET/CT impacted patients' disease management in 70% of cases, 60% of case when PSA was less than 2 ng/ml. This management was considered as adequate in 91% of patients. PSMA-11 PET/CT appeared to be effective in restaging patients with castration-resistant nonmetastatic PCa. PSMA-11 PET/CT should be considered as a replacement for bone scans under these conditions.

This study used nanofluidic protein posttranslational modification (PTM) profiling to measure the effects of six cannabidiol (CBD) oils and isolated CBD on the signaling pathways of a cultured SH-SY5Y neuronal cell line. Chemical composition analysis revealed that all CBD oils met the label claims and legal regulatory limit regarding the CBD and tetrahydrocannabinol (THC) contents, respectively. Isolated CBD was cytotoxic, with an effective concentration (EC 50 ) of 40 µM. In contrast, the CBD oils had no effect on cell viability at CBD concentrations exceeding 1.2 mM. Interestingly, only an unadulterated CBD oil had strong and statistically significant suppressive effects on the pI3K/Akt/mTOR signaling pathway with an EC 50 value of 143 µM and a slow-acting timescale requiring hours. Systematic profiling of twenty-six proteins, which served as biomarkers for nine signaling pathways, revealed that the unadulterated CBD oil downregulated seven signaling pathways but had no measurable effect on the other two signaling pathways. The remaining CBD oils, which were adulterated, and isolated CBD had weak, variable, or undetectable effects on neuronal signaling pathways. Our data clearly showed that adulteration diminished the biological activities of CBD oils. In addition, nanofluidic protein PTM profiling provided a robust means for potency assessment of CBD oils., Competing Interests: The authors declare no conflicts of interest. C.B., M.W., and D.K.H. are employees of dōTERRA International. Currently, dōTERRA International does not produce or sell hemp extracts or cannabinoid products. D.K.H. and C.B. participated in the initial conceptualization of the project. C.B. and M.W. analyzed the chemical composition of CBD oils purchased from the open market using HPLC and GC-MS methods. Data collected by C.B. and M.W. were compared side by side with those collected independently by the Aromatic Plant Research Center and Botanacor.

Background : Electronic platform surveys are ideal for self-administration in adolescent populations, as nearly all adolescents in the US report using or having access to smartphones. This technology-savvy population seems prepared to graduate away from paper surveys. Despite predicted advantages of using smartphones for data collection, there is a surprising lack of data regarding the use of this mode for surveillance of substance use trends among adolescent populations. Objectives : The objective of this study was to evaluate completion rates, times, and responses of high school students taking the Secondary Student Life Survey: Nevada (SSLS:NV) on their own personal smartphones compared to provided computers or tablets. Methods: The SSLS:NV is a web-based survey designed to assess adolescent beliefs, attitudes, and use-trends surrounding substance use. The SSLS:NV was self-administered via self-selected device (personal vs. provided) within one class period to approximately one thousand 9th-12th grade students in December 2016. Data was collected and analyzed to compare outcomes by computer, tablet, or smartphone. Statistical analysis was performed in SPSS 23.0 using χ 2 or Fisher's exact test for categorical data and one-way ANOVA for continuous data. Results : SSLS:NV completion times averaged 21 min overall ( p  = .193). Differences were seen with completion rates of 86% smartphone 94% tablet, and 95% computer ( p  < .001), while responses to lifetime substance use were similar across all groups. Conclusions/Importance : The current study provides proof of concept that personal smartphones are effective in achieving more comprehensive adolescent substance use surveillance within a relatively short amount of time, while retaining robust response rates.

Brown tumors are rare skeletal anomalies occurring in patients with hyperparathyroidism and exposing patients to pathological fractures. We report the case of a 26-year-old woman with severe primary hyperparathyroidism (calcemia, 2.9 mmol/L; parathyroid hormone, 59 pmol/L) who underwent F-fluorocholine (FCH) PET/CT before parathyroidectomy. FCH PET localized the hyperfunctioning parathyroid gland and showed multiple foci in correspondence with bone lytic lesions on CT. Those lesions were not visible on the Tc-MIBI dual-phase scintigraphy. The pathology of one of the FCH-positive bone lesions corresponded to a brown tumor related to hyperparathyroidism.

Introduction: Primary hyperparathyroidism (PHPT) during pregnancy can be responsible for serious maternal and foetal complications and should be treated by elective low-risk, minimally invasive surgery. Preoperative assessment of hyperfunctioning parathyroid glands is classically based on high-resolution neck ultrasound (US) and 99m Tc-sestamibi/ 123 I scintigraphy. However, administration of any radiopharmaceutical during pregnancy must be limited and justified and US alone may be sufficient to localize an abnormal parathyroid gland., Case Report: We report the case of a 4-month pregnant woman with severe primary hyperparathyroidism, in whom US failed to localize the abnormal parathyroid gland. 99m Tc-sestamibi scintigraphy was performed in preference to 18 -fluorocholine (FCH)-PET/CT on the basis of a multidisciplinary decision. As 99m Tc-MIBI demonstrated an hyperfunctioning right inferior parathyroid, 123 I was not administered. A large right paravertebral parathyroid adenoma was successfully removed, as confirmed by decreased postoperative serum parathyroid hormone and calcium levels. The eutrophic newborn infant was delivered at term, with normal serum calcium and TSH levels., Discussion: In pregnant women with primary hyperparathyroidism, US alone may be sufficient when it localizes the abnormal parathyroid gland, allowing elective low-risk minimally invasive surgery. Otherwise, a multidisciplinary approach is mandatory to select the radiopharmaceutical that can be safely used to identify the hyperfunctioning parathyroid gland with minimal risks for the foetus., (Copyright © 2019. Published by Elsevier Masson SAS.)

Background & Aims: In one-third of hepatocellular carcinomas (HCCs), cancer cells have mutations that activate β-catenin pathway. These cells have alterations in glutamine, bile, and lipid metabolism. We investigated whether positron emission tomography (PET) imaging allows identification of altered metabolic pathways that might be targeted therapeutically., Methods: We studied mice with activation of β-catenin in liver (Apc ko-liv mice) and male C57Bl/6 mice given injections of diethylnitrosamine, which each develop HCCs. Mice were fed a conventional or a methionine- and choline-deficient diet or a choline-deficient (CD) diet. Choline uptake and metabolism in HCCs were analyzed by micro-PET imaging of mice; livers were collected and analyzed by histologic, metabolomic, messenger RNA quantification, and RNA-sequencing analyses. Fifty-two patients with HCC underwent PET imaging with 18 F-fluorodeoxyglucose, followed by 18 F-fluorocholine tracer metabolites. Human HCC specimens were analyzed by immunohistochemistry, quantitative polymerase chain reaction, and DNA sequencing. We used hepatocytes and mouse tumor explants for studies of incorporation of radiolabeled choline into phospholipids and its contribution to DNA methylation. We analyzed HCC progression in mice fed a CD diet., Results: Livers and tumors from Apc ko-liv mice had increased uptake of dietary choline, which contributes to phospholipid formation and DNA methylation in hepatocytes. In patients and in mice, HCCs with activated β-catenin were positive in 18 F-fluorocholine PET, but not 18 F-fluorodeoxyglucose PET, and they overexpressed the choline transporter organic cation transporter 3. The HCC cells from Apc ko-liv mice incorporated radiolabeled methyl groups of choline into phospholipids and DNA. In Apc ko-liv  mice, the methionine- and choline-deficient diet reduced proliferation and DNA hypermethylation of hepatocytes and HCC cells, and the CD diet reduced long-term progression of tumors., Conclusions: In mice and humans, HCCs with mutations that activate β-catenin are characterized by increased uptake of a fluorocholine tracer, but not 18 F-fluorodeoxyglucose, revealed by PET. The increased uptake of choline by HCCs promotes phospholipid formation, DNA hypermethylation, and hepatocyte proliferation. In mice, the CD diet reverses these effects and promotes regression of HCCs that overexpress β-catenin., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the impact of 18F-sodium-fluoride (NaF) PET/CT, 18F-fluorocholine (FCH) PET/CT and diffusion-weighted whole-body MRI (DW-MRI) on the management of patients with prostate cancer (PCa) suspicious for distant metastasis., Methods: Prostate cancer patients were prospectively included between December 2011 and August 2014 and benefited from these three whole-body imaging (WBI) modalities within 1 month in addition to the standard PCa workup. Management was prospectively decided by clinicians during two multidisciplinary meetings, before and after the whole-body imaging workup. Rates of induced changes of whole-body imaging modalities were compared by Cochran's Q test., Results: One-hundred-one patients (27 at staging, 59 at first biochemical recurrence (BCR) and 15 at first episode of rising serum level of prostate-specific antigen during androgen-deprivation therapy) were included. The overall rate of management changes was 52%: 29% as a consequence of WBI, higher for FCH-PET/CT than for NaF-PET/CT or DW-MRI (p < 0.0001) and highest (41%) for FCH-PET/CT at BCR. Actual management was adequate in all patients but two., Conclusions: Whole-body imaging induced a change in management in approximately a third of PCa patients suspicious for metastasis. The impact rate was determined to be greatest at first BCR using FCH-PET/CT. NaF-PET/CT and DW-MRI seemed less useful in this context.

Neurotensin receptor 1 (NTSR1) is overexpressed in human pancreatic ductal adenocarcinoma (PDAC). Specific noninvasive positron-emission tomography (PET) imaging probes may improve the diagnostic accuracy and the monitoring of therapy for patients with PDAC. Here, we report the use of the 68 Ga-labeled neurotensin (NTS) analogue DOTA-NT-20.3 to image human PDAC in animal models and to discriminate tumors from pancreatitis. In addition to the preclinical study, two tissue microarray slides, constructed by small core biopsies (2-5) from standard paraffin-embedded tumor tissues, were used to confirm the high (78%) positivity rate of NTSR1 expression in human PDAC. PET imaging, biodistribution, blocking, and histology studies were performed in subcutaneous AsPC-1 pancreatic tumor-bearing mice. 68 Ga-DOTA-NT-20.3 PET images showed rapid tumor uptake and high contrast between the tumor and background with a fast blood clearance and a moderate accumulation in the kidneys. Ex vivo biodistribution showed low uptake in normal pancreas (0.22% IA/g) and in the remaining organs at 1 h postinjection, kidney retention (5.38 ± 0.54% IA/g), and fast clearance from blood and confirmed high uptake in tumors (5.28 ± 0.93% IA/g), leading to a tumor-to-blood ratio value of 6 at 1 h postinjection. The significant decrease of tumor uptake in a blocking study demonstrated the specificity of 68 Ga-DOTA-N-T20.3 to target NTSR1 in vivo. PET imaging was also conducted in an orthotopic xenograft model that allows tumors to grow in their native microenvironment and in an experimental pancreatitis model generated by caerulein injections. As opposed to 2-[ 18 F]fluoro-deoxyglucose, 68 Ga-DOTA-NT-20.3 distinguishes PDAC from pancreatitis. Thus, 68 Ga-DOTA-NT-20.3 is a promising PET imaging probe for imaging PDAC in humans.

Purpose: The aim of this study was to evaluate positron emission tomography (PET) imaging with [ 68 Ga]NODAGA-c(RGDfK) ([ 68 Ga]RGD), in comparison with 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG), for early monitoring of the efficacy of an antiangiogenic agent associated or not with chemotherapy, in a mouse model of glioblastoma (GB)., Procedures: Mice bearing U87MG human GB cells line were parted into five groups of five mice each. One group was imaged at baseline before the treatment phase; another group was treated with bevacizumab (BVZ), another group with temozolomide (TMZ), another group with both agents, and the last one was the control group. Tumors growth and biological properties were evaluated by caliper measurements and PET imaging at three time points (baseline, during treatment t1 = 4-6 days and t2 = 10-12 days). At the end of the study, tumors were counted and analyzed by immunohistochemistry (CD31 to evaluate microvessel density)., Results: The tumor volume assessed by caliper measurements was significantly greater at t1 in the control group than in the TMZ + BVZ-treated group or in the BVZ-treated group. At t2, tumor volume of all treated groups was significantly smaller than that of the control group. [ 18 F]FDG PET failed to reflect this efficacy of treatment. In contrast, at t1, the [ 68 Ga]RGD tumor uptake was concordant with tumor growth in controls and in treated groups. At t2, a significant increase in tumor uptake of [ 68 Ga]RGD vs. t1 was only observed in the TMZ-treated group, reflecting a lack of angiogenesis inhibition, whereas TMZ + BVZ resulted in a dramatic tumor arrest, reduction in microvessel density and stable tumor [ 68 Ga]RGD uptake., Conclusions: [ 68 Ga]RGD is a useful PET agent for in vivo angiogenesis imaging and can be useful for monitoring antiangiogenic treatment associated or not with chemotherapy.

Despite their relative quiescence, pancreatic neuro-endocrine tumors (pNET) can correspond to various presentations and outcomes. Several prognostic factors have been identified, including maximal standardized uptake value of the most intense focus (maxSUVmax) on Positron Emission Tomography (PET) with a somatostatin analogue. Herein, we investigate the prognostic value on progression free-survival of the total functional tumor volume (TFTV) measured by 68Ga-DOTATOC PET. From patients who underwent 68Ga-DOTATOC PET from 2008 to 2014, we selected consecutive patients with G1 or G2 pNET (2010 World Health Organization classification), at least one abnormal focus on PET and available follow-up data. TFTV was computed by summing the volumes of all pathological foci, delineated use of 41% of its SUVmax for each threshold focus. Fifty patients were included. During the follow-up period, 33 patients had stable or responsive disease (66%; median duration 28.5 months; range 6.3-77.7 months) and 17 patients experienced disease progression (34%; median progression time 21 months; range 6.7-44.7 months). Median PFS was 43.5 months. The best TFTV cut-off for predicting progression within 24 months was 13.8 cm3. Multivariate analysis determined that TFTV greater than 13.8 cm3 was the only criterion considered a significant risk factor for tumor progression (HR 2.9; p=0.0003). A significant difference in PFS was observed for TFTV (<13.8 vs. ≥ 13.8 cm3: median not reached vs. 25 months; p=0.0001). Our study suggests that 68Ga-DOTATOC TFTV measured on PET images is a valuable prognostic biomarker in patients with well-differentiated pNETs of all stages.

Oligometastatic disease represents a clinical and anatomical manifestation between localised and polymetastatic disease. In prostate cancer, as with other cancers, recognition of oligometastatic disease enables focal, metastasis-directed therapies. These therapies potentially shorten or postpone the use of systemic treatment and can delay further metastatic progression, thus increasing overall survival. Metastasis-directed therapies require imaging methods that definitively recognise oligometastatic disease to validate their efficacy and reliably monitor response, particularly so that morbidity associated with inappropriately treating disease subsequently recognised as polymetastatic can be avoided. In this Review, we assess imaging methods used to identify metastatic prostate cancer at first diagnosis, at biochemical recurrence, or at the castration-resistant stage. Standard imaging methods recommended by guidelines have insufficient diagnostic accuracy for reliably diagnosing oligometastatic disease. Modern imaging methods that use PET-CT with tumour-specific radiotracers (choline or prostate-specific membrane antigen ligand), and increasingly whole-body MRI with diffusion-weighted imaging, allow earlier and more precise identification of metastases. The European Organisation for Research and Treatment of Cancer (EORTC) Imaging Group suggests clinical algorithms to integrate modern imaging methods into the care pathway at the various stages of prostate cancer to identify oligometastatic disease. The EORTC proposes clinical trials that use modern imaging methods to evaluate the benefits of metastasis-directed therapies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: To develop criteria to improve discrimination between vertebral metastases from neuroendocrine tumours (NETs) and benign bone lesions on PET combined with CT using DOTA-D-Phe 1 -Tyr 3 -octreotide labelled with gallium-68 ( 68 Ga-DOTA-TOC)., Methods: In 535 NET patients, 68 Ga-DOTA-TOC PET/CT examinations were reviewed retrospectively for vertebral CT lesions and/or PET foci. For each vertebral PET abnormality, appearance on CT, biological volume (BV), standardized uptake value (SUV max ) and ratios to those of reference organs were determined. All vertebral abnormalities were characterized as a metastasis, a typical vertebral haemangioma (VH) or other benign lesion., Results: In 79 patients (14.8 %), we found 107 metastases, 34 VHs and 31 other benign lesions in the spine. The optimal cut-off values to differentiate metastases from benign lesions were BV ≥0.72 cm 3 , SUVmax ≥2, SUVmax ratio to a reference vertebra ≥2.1, to liver ≥0.28 and to spleen ≥0.14. They corresponded to lesion-based 68 Ga-DOTA-TOC PET/CT sensitivity of 87 %, 98 %, 97 %, 99 % and 94 %, and specificity of 55 %, 100 %, 90 %, 97 %, 100 %, respectively., Conclusions: The high sensitivity of 68 Ga-DOTA-TOC-PET/CT in detecting NET vertebral metastases was confirmed; this study showed that specificity could be improved by combining CT features and quantifying 68 Ga-DOTA-TOC uptake., Key Points: • Bone metastases in neuroendocrine tumours correlate with prognosis. • Benign bone lesions may mimic metastases on 68 Ga-DOTA-TOC PET/CT imaging. • The specific polka-dot CT pattern may be missing in some vertebral haemangiomas. • Lesion atypical for haemangiomas can be better characterized by quantifying 68 Ga-DOTA-TOC uptake.

Purpose: Oncogenic osteomalacia is an endocrine disorder induced by small benign tumours (TIO) producing excessive fibroblast growth factor-23 (FGF23). The only way of curing oncogenic osteomalacia is surgical resection of the culprit TIO, which is extremely difficult to detect using conventional imaging modalities due to its small size and variable location in the body. Since TIO frequently overexpress somatostatin receptors, a clinical utility of SPECT or PET with radiolabelled somatostatin analogues has been reported. Among them, 68 Ga-DOTA-TOC has recently been granted a marketing authorization, facilitating its routine application. We report here the results of the first series evaluating the diagnostic performance of 68 Ga-DOTA-TOC PET/CT in detecting TIO and its impact on patient management., Methods: 68 Ga-DOTA-TOC PET/CT and clinical and imaging data from 15 patients with clinical and biochemical signs of oncogenic osteomalacia were retrospectively reviewed. The 68 Ga-DOTA-TOC PET/CT findings were compared with the results of post-surgical pathology and clinical and biochemical follow-up., Results: 68 Ga-DOTA-TOC PET/CT resulted in the detection of one focus suspicious for TIO in nine of 15 patients (60%), and a tumour was surgically removed in eight. Post-operative pathology confirmed a TIO in those eight patients whose symptoms diminished promptly and biochemical anomalies resolved. 68 Ga-DOTA-TOC PET/CT sensitivity, specificity and accuracy were 73%, 67% and 71%, respectively. 68 Ga-DOTA-TOC PET/CT findings affected patient management in 67% of cases. In particular, 68 Ga-DOTA-TOC PET/CT was able to detect the TIO with a negative or a false-positive result of a previous 111 In-pentetreotide SPECT/CT in 5/8 patients (63%) or a previous FDG PET/CT in 7/11 patients (64%). No close relationship was found between the positivity of 68 Ga-DOTA-TOC PET/CT and the serum level of a biochemical marker. However, a true-positive result of 68 Ga-DOTA-TOC PET/CT was obtained in only one patient with a non-elevated serum level of FGF23., Conclusion: 68 Ga-DOTA-TOC PET/CT is an accurate imaging modality in the detection of TIO; in particular, it is worthwhile after failure of somatostatin receptor SPECT(/CT) or FDG PET/CT.

Ro 25-6981 is a highly potent and selective blocker of N-methyl-d-aspartate receptors that has been shown to possess both rapid and sustained antidepressant activity. In the present study, we report the biopharmaceutical characterization of Ro 25-6981 by evaluating gastrointestinal stability, transepithelial permeability, stability in human liver microsomes, and in silico metabolic prediction. Moreover, in vivo efficacy of Ro 25-6981 after oral administration was evaluated in animal models of depression. When mixed with 5 different simulated gastrointestinal fluids, no loss of parent compound was observed after 6 h, indicating compound stability in the gastrointestinal environment. At the tested concentrations, Ro 25-6981 was shown to have transepithelial permeability with apparent permeability (P app ) values comparable to highly permeable drugs. Ro 25-6981 was metabolized within 30 min in human liver microsomes, and the metabolic prediction data showed glucuronidation and sulfation as potential metabolic pathways. The in vivo efficacy data suggested that Ro 25-6981, when administered orally at 30 mg/kg, exhibits antidepressant-like activity following oral administration with efficacy comparable to traditional antidepressants that is both dose- and time-dependent. Overall, due to optimal gastrointestinal stability, oral permeability, and oral efficacy, Ro 25-6981 can be a potential therapeutic option for the treatment of depression., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)