18F-Fluorocholine-Positron Emission Tomography/Computerized Tomography (FCH PET/CT) Imaging for Detecting Abnormal Parathyroid Glands: Indication, Practice, Interpretation and Diagnostic Performance.

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.

EANM guidelines on the use of [18F]FDG PET/CT in diagnosis, staging, prognostication, therapy assessment, and restaging of plasma cell disorders.

We provide updated guidance and standards for the indication, acquisition, and interpretation of [18F]FDG PET/CT for plasma cell disorders. Procedures and characteristics are reported and different scenarios for the clinical use of [18F]FDG PET/CT are discussed. This document provides clinicians and technicians with the best available evidence to support the implementation of [18F]FDG PET/CT imaging in routine practice and future research.

Glycomimetic inhibitors of tandem-repeat galectins: Simple and efficient.

The binding of human galectins by glycomimetic inhibitors is a promising therapeutic approach. The structurally distinct group of tandem-repeat galectins has scarcely been studied so far, and there is hardly any knowledge on their ligand specificity or their inhibitory potential, particularly concerning non-natural carbohydrates. Here, we present the synthesis of a library of seven 3-O-disubstituted thiodigalactoside-derived glycomimetics and their affinity to two tandem-repeat galectins, Gal-8 and Gal-9. The straightforward synthesis of these glycomimetics involved dibutyltin oxide-catalyzed 3,3́-O-disubstitution of commercially available unprotected thiodigalactoside, and conjugation of various aryl substituents by copper-catalyzed Huisgen azide-alkyne cycloaddition (CuAAC). The inhibitory potential of the prepared glycomimetics for Gal-8 and Gal-9 was assessed, and compared with the established galectins Gal-1 and Gal-3. The introduction of C-3 substituents resulted in an over 40-fold increase in affinity compared with unmodified TDG. The structure-affinity relations within the studied series were discussed using molecular modeling. Furthermore, the prepared glycomimetics were shown to scavenge Gal-8 and Gal-9 from the surface of cancer cells. This pioneering study on the synthetic inhibitors especially of Gal-9 identified lead compounds that may be used in further biomedical research.

Summary: SNMMI Procedure Standard/EANM Practice Guideline for Estrogen Receptor Imaging of Patients with Breast Cancer Using 16α-[18F]Fluoro-17ß-Estradiol PET.

The estrogen receptor (ER), a steroid hormone receptor important in female physiology, is a significant contributor to breast carcinogenesis and progression and, as such, is an important therapeutic target. Approximately 70% of breast cancers will express ER at presentation, and the determination of ER expression by tissue assay, usually by immunohistochemistry, is part of the standard of care for newly diagnosed breast cancer. ER expression is important in guiding the approach to treatment, especially with the increase in relevant systemic therapies. The ER-targeting imaging agent 16α-[18F]fluoro-17ß-estradiol ([18F]FES) is approved for clinical use by regulatory agencies in France and the United States. Multiple studies suggest the advantages of [18F]FES PET in assessing tumor ER expression, the ability of both qualitative and quantitative [18F]FES PET measures to predict response to ER-targeted therapy, and the ability of [18F]FES PET to clarify equivocal staging and restaging results in patients with ER-expressing cancers. [18F]FES PET/CT may also be helpful in staging invasive lobular breast cancer and low-grade ER-expressing invasive ductal cancers and, in some cases, may be a substitute for biopsy. The Society of Nuclear Medicine and Molecular Imaging and the European Association of Nuclear Medicine in June 2023 released a procedure standard/practice guideline for [18F]FES PET ER imaging of patients with breast cancer. The goal of the standard/guideline is to assist physicians in recommending, performing, interpreting, and reporting the results of [18F]FES PET studies for patients with breast cancer and to provide clinicians with the best available evidence, inform them about areas where robust evidence is lacking, and help them deliver the best possible diagnostic efficacy and study quality for their patients. Also reviewed are standardized quality control, quality assurance, and imaging procedures for [18F]FES PET. The authors emphasize the importance of precision, accuracy, repeatability, and reproducibility for both clinical management of patients and for use of [18F]FES PET in multicenter trials. A standardized imaging procedure, in combination with already published appropriate-use criteria, will help promote the use of [18F]FES PET and enhance subsequent research. This brief summary article reviews the content of the joint standard/guideline, which is available in its entirety at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=6414&navItemNumbe=10790.

The Presence of an Arteria Lusoria Should Be Checked When Reporting 18 F-FCH PET/CT Performed to Localize Hyperfunctioning Parathyroid Glands.

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.

18F-fluorocholine PET/CT detects parathyroid gland hyperplasia as well as adenoma: 401 PET/CTs in one center.

BACKGROUND: During the past decade, 18F-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 1st 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 99mTc-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 1st 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.

Interference of Known or Suspected Endometriosis in Reporting FDG PET/CT Performed in Another Indication.

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.

Multiple endocrine neoplasia type 1 or 4: detection of hyperfunctioning parathyroid glands with 18F-fluorocholine PET/CT. Illustrative cases and pitfalls.

18F-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.

Hepatic Cavernous Hemangioma Mimicking Metastasis of Midgut Neuroendocrine Neoplasia on 18F-Fluorodihydroxyphenylalanine PET/CT.

ABSTRACT: A 61-year-old man after resection of well-differentiated midgut neuroendocrine neoplasia (NEN) was referred to 18F-fluorodihydroxyphenylalanine PET/CT for localization of recurrent midgut NEN in the context of clinical symptoms and mild elevation of serum CgA (chromogranin A) levels. Isolated hepatic focus of increased 18F-Fluorodihydroxyphenylalanine uptake was detected. The biopsy of this focus, followed by radiofrequency ablation, revealed a hepatic cavernous hemangioma. Complete remission of midgut NEN was confirmed during 4-year clinical and imaging follow-up. The persistent mild elevation of serum CgA was retrospectively attributed to treatment with proton-pump inhibitors.

Case Report: Skeletal Muscle Lymphoma as a Result of Slow Centrifugal Migration of Untreated Primary Neurolymphomatosis?

Introduction: Fludeoxyglucose (18F) (FDG) hybrid positron emission tomography/computed tomography (PET/CT) is currently a well-documented tool for diagnosis, staging, and therapeutic follow-up of lymphoma with significant impact on therapeutic decisions. Patient Concerns and Interventions: We reported a case of a 71-year-old woman with diffuse large B-cell lymphoma (DLBCL) of the left gluteal muscles as a possible result of slow centrifugal migration of untreated neurolymphomatosis (NL) of the lumbosacral plexus suggested on FDG PET/CT 4 years ago, when the patient was complaining for weakness and numbness of the left leg, but the proposed biopsy of peripheral nerve was not performed. Four years later, no pathological FDG uptake was present in nerves and lymph nodes, but PET/CT detected multiple FDG-positive infiltrates in the left gluteal muscles, appearing as a continuation of previously involved nerves. Diagnosis: The biopsy of muscular infiltrates confirmed DLBCL. Outcomes: The therapy was started, and a complete remission was achieved after three lines of treatment. Conclusion: This case contributes to limited knowledge on development of skeletal muscle lymphoma (SML): It suggests the macroscopically isolated, FDG-positive SML involving more than one muscular compartment as a possible consequence of natural course of untreated primary NL previously revealed by peripheral neuropathy and suspected on FDG PET/CT. This observation further justifies the consideration of implementation of FDG PET/CT into diagnostic algorithm while evaluating the peripheral neuropathy, in which the NL, albeit rare, is a part of differential diagnosis.

Stage I testicular seminoma risk-adapted therapeutic management.

Following orchiectomy, patients with clinical stage I (CSI) testicular seminoma may be managed by active surveillance (S) or adjuvant treatment (radiotherapy or chemotherapy). In view of the published data on long-term toxicity, especially second malignant neoplasms (SMNs), adjuvant radiotherapy (ART) is currently no longer recommended as an adjuvant therapy option for these patients. The purpose of our recent study was to compare the impact of two selected treatment approaches - S versus adjuvant chemotherapy (ACT) on the survival of patients with CSI testicular seminoma. This cross-sectional study analyzed a total of 139 patients collected at a single center between 10/2011-5/2020, with CSI testicular seminoma, stratified into two groups according to risk-adapted therapeutic approaches. In the S group (low-risk - without rete testis invasion - RTI, primary tumor size <4 cm), consisting of 77 patients, who underwent S, relapse occurred in 10 (13.0%) patients after a mean follow-up of 14.3 months. In the ACT group (high-risk - RTI and/or primary tumor size >4 cm), consisting of 62 patients, who were treated with ACT, relapse occurred in 5 (8.1%) patients after a mean follow-up of 11.6 months. Overall survival of patients in both groups was 100% with a mean follow-up of 43.9 months. A statistically significant difference in progression-free survival (PFS) between these two groups was not found. Based on our findings, ACT seems to be an adequate treatment for patients with a high risk of relapse, as well as S for those with a low risk of relapse. Despite its excellent prognosis, optimal management of CSI testicular seminoma remains controversial, with variations in expert opinion and international guidelines.

Comparison of 18F-sodium fluoride PET/CT, 18F-fluorocholine PET/CT and diffusion-weighted MRI for the detection of bone metastases in recurrent prostate cancer: a cost-effectiveness analysis in France.

BACKGROUND: The diagnostic performance of 18F-sodium fluoride positron emission tomography/computed tomography (PET/CT) (NaF), 18F-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.

European Association of Nuclear Medicine Practice Guideline/Society of Nuclear Medicine and Molecular Imaging Procedure Standard 2019 for radionuclide imaging of phaeochromocytoma and paraganglioma.

PURPOSE: Diverse radionuclide imaging techniques are available for the diagnosis, staging, and follow-up of phaeochromocytoma and paraganglioma (PPGL). Beyond their ability to detect and localise the disease, these imaging approaches variably characterise these tumours at the cellular and molecular levels and can guide therapy. Here we present updated guidelines jointly approved by the EANM and SNMMI for assisting nuclear medicine practitioners in not only the selection and performance of currently available single-photon emission computed tomography and positron emission tomography procedures, but also the interpretation and reporting of the results. METHODS: Guidelines from related fields and relevant literature have been considered in consultation with leading experts involved in the management of PPGL. The provided information should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals. CONCLUSION: Since the European Association of Nuclear Medicine 2012 guidelines, the excellent results obtained with gallium-68 (68Ga)-labelled somatostatin analogues (SSAs) in recent years have simplified the imaging approach for PPGL patients that can also be used for selecting patients for peptide receptor radionuclide therapy as a potential alternative or complement to the traditional theranostic approach with iodine-123 (123I)/iodine-131 (131I)-labelled meta-iodobenzylguanidine. Genomic characterisation of subgroups with differing risk of lesion development and subsequent metastatic spread is refining the use of molecular imaging in the personalised approach to hereditary PPGL patients for detection, staging, and follow-up surveillance.

18F-fluorocholine PET/CT in patients with occult biochemical recurrence of prostate cancer: Detection rate, impact on management and adequacy of impact. A prospective multicentre study.

AIM: To prospectively evaluate the clinical impact and the diagnostic performance of FCH-PET/CT in patients with occult biochemical recurrence of prostate cancer (PCa). MATERIALS AND METHODS: Results of 179 patients (mean PSA = 7.5ng/mL) with negative/inconclusive results of pelvic-MRI and of bone-scintigraphy were analysed. To determine the impact of FCH-PET/CT on diagnostic thinking and on patient management, the referring physicians prospectively filled-in a 1st and 2nd questionnaire related to patient's planned management before and after FCH-PET/CT. Based on data from a 6-month follow-up after FCH-PET/CT, an independent assessor blinded to results of FCH-PET/CT determined the adequacy of management changes motivated by FCH-PET/CT. RESULTS: FCH-PET/CT localised foci evocative of recurrent PCa in 59% (105/179) of patients. Results of FCH-PET/CT motivated a change in scheduled patient management in 56% (100/179) of patients; which was considered as adequate in 89% (89/100) of patients. FCH-PET/CT also led to the detection of lung cancer in two patients. CONCLUSION: FCH PET/CT is a powerful tool to localise the sites of occult biochemical recurrence of PCa, leading to an adequate management change in half of patients.

Radiosynoviorthesis of acromioclavicular joint using 169Er-citrate: prospective evaluation of efficacy.

BACKGROUND: There is a clinical need for therapeutic alternative in patients with persisting painful arthritis of AC-joint and failure of previous treatments. However, no radiopharmaceutical is currently explicitly approved for radiosynoviorthesis of acromioclavicular joint. The aim of our study was to prospectively assess the efficacy and safety of radiosynoviorthesis of acromioclavicular joint using erbium-169 citrate. MATERIAL AND METHODS: Radiosynoviorthesis of acromioclavicular joint was performed in 51 consecutive patients (18 males, 33 females) mean age 64.3 (range 43.8-82.6, median 63.6) years with clinically confirmed arthritis of 85 acromioclavicular joints. The efficacy of RSO was reported by patients according to 10-step visual analogue scale of pain (VAS) (0 = no pain, 10 = most severe pain) at 6 months after radiosynoviorthesis and by ranking the global therapeutic effect of RSO in 4 categories (1 = the best effect, 4 = no change). To assess the variation of blood perfusion in treated joints, the efficacy of RSO was also evaluated by variation of target (acromioclavicular joint)/non-target (soft tissue) uptake ratio (T/NTR) of metylendiphosphonate (99mTc) measured as number of counts over region of interest on blood pool phase of two-phase bone scintigraphy performed before and 6 months after RSO. RESULTS: Radiosynoviorthesis was followed by significant decrease in VAS, mean - 3.1 (-47%). Excellent, good, moderate and bad response was observed in 57 (67%), 25 (29%), 1 (1%) and in 2 (2%) of acromioclavicular joints respectively. A significant correlation between decrease of T/NTR and variation of VAS in % (ρ = 0.532, p < 0.0001) and between T/NTR and subjective evaluation of therapeutic effect in scale 1-4 (ρ = 0.388, p = 0.0002) was observed. However, it was not possible to identify the cut-off value of relative decrease in T/NTR showing sufficient sensitivity and specificity to detect the therapeutic response. CONCLUSION: Results of this prospective study permit to conclude a good efficacy and safety of radiosynoviorthesis using erbium-169 citrate in a series of patients with arthritis of acromioclavicular joint in whom previous line(s) of treatment did not lead to satisfactory pain relief.

Guideline for PET/CT imaging of neuroendocrine neoplasms with 68Ga-DOTA-conjugated somatostatin receptor targeting peptides and 18F-DOPA.

PURPOSE & METHODS: Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using 68Ga-DOTA-conjugated peptides, as well as 18F-DOPA imaging for various neuroendocrine neoplasms. RESULTS & CONCLUSION: The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with 68Ga-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts.