Outcome on Mesenteric Mass Response of Small-Intestinal Neuroendocrine Tumors Treated by 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy: The MesenLuth Study, a National Study from the French Group of Endocrine Tumors and Endocan-RENATEN Network.

A mesenteric mass (MM), characterized by fibrotic reaction, is present in most small-intestinal neuroendocrine tumors (SI-NETs). 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) has shown its efficacy in patients with progressive SI-NETs. However, because of specific tissue characteristics of desmoplastic MMs, we hypothesize that these lesions may be refractory to 177Lu-DOTATATE PRRT. Methods: From the national French Groupe d'étude des Tumeurs Endocrines database, we identified patients with an advanced SI-NET and a MM (≥2 cm with a retractile aspect) of a SI-NET treated by at least 1 course of 177Lu-DOTATATE PRRT. The primary endpoint was a MM objective response rate (ORR) of less than 5%. Secondary endpoints were metabolic response, MM-related safety, and clinical response, as well as MM progression-free survival (PFS) and non-MM PFS. Results: In total, 52 patients were included. The MM ORR was 4% (n = 2), and the non-MM ORR was 8% (n = 4). No patient had a MM metabolic response, and the non-MM metabolic response rate was 12% (n = 6). Among the 26 patients with baseline MM-related symptoms, 46% had a clinical response. Four patients presented with gastrointestinal complications during PRRT. The median MM-related PFS was not reached, and the non-MM PFS was 50.3 mo (95% CI, 38.2-61.7 mo). Conclusion: This study confirms that 177Lu-DOTATATE PRRT does not lead to morphologic response on MMs (ORR < 5%). However, it allows MM stability, with few MM-related side effects, and has a relevant impact on MM-related symptoms.

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

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

Dual-tracer 99mTc-sestamibi/ 123I imaging in primary hyperparathyroidism.

Surgery is the only curative treatment for primary hyperparathyroidism (PHPT). Preoperative imaging is always recommended. 99mTc-sestamibi scintigraphy is often used in combination with neck ultrasonography as first-line imaging. 99mTc-sestamibi scintigraphy plays a major role in depicting ectopic parathyroid lesions, as well as in guiding a targeted, minimally invasive parathyroidectomy (MIP). Detecting multiple gland disease (MGD) is important to reduce the risks of surgical failure or unplanned conversion to bilateral surgery. However, the ability to recognize MGD varies greatly depending on the 99mTc-sestamibi imaging protocol that is used. Dual-tracer 99mTc-sestamibi/123I highly improves MGD detection compared to single-tracer "dual-phase" 99mTc-sestamibi imaging. It can thus improve patient selection for MIP. The main requirements for successful dual-tracer imaging are: 1) to acquire 99mTc-sestamibi and 123-iodine images simultaneously, thus avoiding motion artifacts on subtraction images; to use neck pinhole imaging, in addition to planar imaging, to improve resolution and MGD detection; to follow with dual-tracer SPECT/CT imaging to better define anatomic position of detected parathyroid lesions. If dual-tracer 99mTc-sestamibi/123I and neck ultrasonography are negative or inconclusive, the second-line imaging in our practice is 18F-fluorocholine PET/CT. The CT component of 18F-fluorocholine PET/CT is performed as non-enhanced acquisition plus a contrast-enhanced arterial phase acquisition, to minimize the risk from false-positives due to choline uptake in inflammatory lymph nodes. We use the same strategy of first-line dual-tracer 99mTc-sestamibi/123I plus neck ultrasonography, followed if necessary by second-line contrast-enhanced 18F-fluorocholine PET/CT, in patients requiring reoperation for persistent or recurrent PHPT. Additional localization techniques are now rarely necessary.

Nuclear Imaging in Pediatric Cardiology: Principles and Applications.

Nuclear imaging plays a unique role within diagnostic imaging since it focuses on cellular and molecular processes. Using different radiotracers and detection techniques such as the single photon emission scintigraphy or the positron emission tomography, specific parameters can be assessed: myocardial perfusion and viability, pulmonary perfusion, ventricular function, flow and shunt quantification, and detection of inflammatory processes. In pediatric and congenital cardiology, nuclear imaging can add complementary information compared to other imaging modalities such as echocardiography or magnetic resonance imaging. In this state-of-the-art paper, we appraise the different techniques in pediatric nuclear imaging, evaluate their advantages and disadvantages, and discuss the current clinical applications.

Diagnostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography Computed Tomography in Prosthetic Pulmonary Valve Infective Endocarditis.

OBJECTIVES: The aim of this study was to assess the diagnostic performances of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in congenital heart disease (CHD) patients with pulmonary prosthetic valve or conduit endocarditis (PPVE) suspicion. BACKGROUND: PPVE is a major issue in the growing CHD population. Diagnosis is challenging, and usual imaging tools are not always efficient or validated in this specific population. Particularly, the diagnostic yield of 18F-FDG PET/CT remains poorly studied in PPVE. METHODS: A retrospective multicenter study was conducted in 8 French tertiary centers. Children and adult CHD patients who underwent 18F-FDG PET/CT in the setting of PPVE suspicion between January 2010 and May 2020 were included. The cases were initially classified as definite, possible, or rejected PPVE regarding the modified Duke criteria and finally by the Endocarditis Team consensus. The result of 18F-FDG PET/CT had been compared with final diagnosis consensus used as gold-standard in our study. RESULTS: A total of 66 cases of PPVE suspicion involving 59 patients (median age 23 years, 73% men) were included. Sensitivity, specificity, positive predictive value, and negative predictive value of 18F-FDG PET/CT in PPVE suspicion were respectively: 79.1% (95% CI: 68.4%-91.4%), 72.7% (95% CI: 60.4%-85.0%), 91.9% (95% CI: 79.6%-100.0%), and 47.1% (95% CI: 34.8%-59.4%). 18F-FDG PET/CT findings would help to correctly reclassify 57% (4 of 7) of possible PPVE to definite PPVE. CONCLUSIONS: Using 18F-FDG PET/CT improves the diagnostic accuracy of the Duke criteria in CHD patients with suspected PPVE. Its high positive predictive value could be helpful in routine to shorten diagnosis and treatment delays and improve clinical outcomes.

Value of Somatostatin Receptor PET/CT in Patients With MEN1 at Various Stages of Their Disease.

CONTEXT: Despite the growing evidence of the clinical value of somatostatin receptor (SSTR) positron emission tomography (PET) in the evaluation of neuroendocrine tumors (NETs), its role remains to be clarified at different time points in the journey of patients with multiple endocrine neoplasia type 1 (MEN1). The rarity of the disease is however a significant impediment to prospective clinical trials. OBJECTIVE: The goals of the study were to assess the indications and value of SSTR PET/computed tomography (CT) in patients with MEN1. METHODS: We retrospectively included patients from 7 French expert centers for whom data on SSTR PET/CT and morphological imaging performed at the same period were available. Detection rates of PET study were analyzed. RESULTS: One hundred and 8 patients were included. SSTR PET/CT was performed at screening (n = 33), staging (n = 34), restaging (n = 37), and for peptide receptor targeted radiotherapy selection (n = 4). PET detected positive pancreatic lesions in 91% of cases at screening, with results comparable with magnetic resonance imaging but superior to CT (P = .049). Metastases (mostly lymph node [LN]) were present at the screening phase in 28% of cases, possibly due to the suboptimal value of screening morphological imaging in the assessment of nodal metastases and/or a long delay between imaging studies. SSTR PET/CT was considered superior or complementary to the reference standard in the assessment of LN or distant metastases in the vast majority of cases and regardless of the clinical scenario. CONCLUSION: This study shows the potential added value of SSTR PET in the assessment of MEN1-associated NETs and provides great impetus toward its implementation in the evaluation of patients with MEN1.

Improved 18-FDG PET/CT diagnosis of multiple myeloma diffuse disease by radiomics analysis.

OBJECTIVES: In multiple myeloma, the diagnosis of diffuse bone marrow infiltration on 18-FDG PET/CT can be challenging. We aimed to develop a PET/CT radiomics-based model that could improve the diagnosis of multiple myeloma diffuse disease on 18-FDG PET/CT. METHODS: We prospectively performed PET/CT and whole-body diffusion-weighted MRI in 30 newly diagnosed multiple myeloma. MRI was the reference standard for diffuse disease assessment. Twenty patients were randomly assigned to a training set and 10 to an independent test set. Visual analysis of PET/CT was performed by two nuclear medicine physicians. Spine volumes were automatically segmented, and a total of 174 Imaging Biomarker Standardisation Initiative-compliant radiomics features were extracted from PET and CT. Selection of best features was performed with random forest features importance and correlation analysis. Machine-learning algorithms were trained on the selected features with cross-validation and evaluated on the independent test set. RESULTS: Out of the 30 patients, 18 had established diffuse disease on MRI. The sensitivity, specificity and accuracy of visual analysis were 67, 75 and 70%, respectively, with a moderate kappa coefficient of agreement of 0.6. Five radiomics features were selected. On the training set, random forest classifier reached a sensitivity, specificity and accuracy of 93, 86 and 91%, respectively, with an area under the curve of 0.90 (95% confidence interval, 0.89-0.91). On the independent test set, the model achieved an accuracy of 80%. CONCLUSIONS: Radiomics analysis of 18-FDG PET/CT images with machine-learning overcame the limitations of visual analysis, providing a highly accurate and more reliable diagnosis of diffuse bone marrow infiltration in multiple myeloma patients.

Prognostic utility of pre-transplantation [18 F] fluorodeoxyglucose positron emission tomography/computed tomography in patients with diffuse large B-cell lymphoma who underwent rituximab, dexamethasone, high-dose cytarabine, carboplatin salvage chemotherapy.

We analysed the outcomes of 62 patients with refractory/relapsed diffuse large B-cell lymphoma (rrDLBCL) who had pre-transplantation fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) after R-DHAC (rituximab, dexamethasone, high-dose cytarabine, carboplatin) salvage chemotherapy, and were evaluated using Deauville criteria and total lesion glycolysis (TLG). A positive pre-transplantation PET/CT with Deauville score of 5 was associated with shorter progression-free survival (PFS) (P = 0·01), while a Deauville score of 4 was not predictive of outcome. Only pre-transplant TLG was significantly associated with both PFS (P = 0·005) and overall survival (P = 0·03). TLG deserves to be further investigated in prospective studies.

Infections in patients using ventricular-assist devices: Comparison of the diagnostic performance of 18F-FDG PET/CT scan and leucocyte-labeled scintigraphy.

BACKGROUND: The usage of left-ventricular-assist device (LVAD) is increasing in patients presenting with advanced heart failure. However, device-related infections are a challenge to recognize and to treat, with an important morbidity and mortality rate. The role of nuclear medicine imaging remains not well established for LVAD infections. The present study compared the accuracy of positron emission tomography/computed tomography with 18F-fludeoxyglucose (18F-FDG PET/CT) and radiolabeled leucocyte scintigraphy for the diagnosis of infections in patients supported with a continuous-flow LVAD. METHODS: From a prospectively maintained database, we retrospectively analyzed the diagnostic performance of radiolabeled leucocyte scintigraphy and 18F-FDG PET/CT in 24 patients who had a LVAD with a suspected device-related infection. Both examinations were routinely performed in all patients. Infection was assessed by the International Society for Heart and Lung Transplantation criteria. RESULTS: Twenty-four patients were included: 15 had a specific VAD infection (5 cardiac-LVAD and 10 driveline), 6 had a VAD-related infection, while 3 patients had a non-VAD-related infection. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.2%, 66.7%, 95.2%, 66.7%, and 91.6%, respectively, for 18F-FDG-PET; and 71.4%, 100%, 100%, 33.3%, and 75%, respectively, for leucocyte scintigraphy. 18F-FDG PET/CT showed significantly higher sensitivity (P = 0.01) than leucocyte scintigraphy. CONCLUSION: 18F-FDG PET/CT and radiolabeled leucocyte scintigraphy single-photon emission computed tomography carry high performance in the diagnostic of LVAD infections. 18F-FDG PET/CT shows significantly higher sensitivity and could be proposed as first-line nuclear medicine procedure.

Galactocele, Pitfall for the Evaluation by 18F-FDG PET/CT.

A high F-FDG uptake was found in mammary lesions in a 36-year-old woman who underwent a PET/CT scan for initial staging of diffuse large B-cell lymphoma. The patient has given birth 2 months ago and was breastfeeding. Ultrasound-guided fine-needle aspiration of 1 lesion yielded creamy liquid consistent with milk and confirmed the diagnosis of galactocele.

Early prosthetic aortic valve infection identified with the use of positron emission tomography in a patient with lead endocarditis.

BACKGROUND: 18-Fluorodeoxyglucose positron emission tomography/computerized tomography (FDG PET/CT) scanning has recently been proposed as a diagnostic tool for lead endocarditis (LE). OBJECTIVE: FDG PET/CT might be also useful to localize associated septic emboli in patients with LE. CASE PRESENTATION: We report an interesting case of a LE patient with a prosthetic aortic valve in whom a trans-esophageal echocardiogram did not show associated aortic endocarditis. FDG PET/CT revealed prosthetic aortic valve infection. A second TEE performed 2 weeks after identified aortic vegetation. A longer duration of antimicrobial therapy with serial follow-up echocardiography was initiated. There was also increased uptake in the sigmoid colon, corresponding to focal polyps resected during a colonoscopy. CONCLUSION: FDG PET/CT scanning seems to be highly sensitive for prosthetic aortic valve endocarditis diagnosis. This promising diagnostic tool may be beneficial in LE patients, by identifying septic emboli and potential sites of pathogen entry.

Contribution of PET Imaging to the Diagnosis of Septic Embolism in Patients With Pacing Lead Endocarditis.

OBJECTIVES: The aim of this study was to investigate the role of 18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scanning in identifying septic embolism in patients with lead endocarditis. BACKGROUND: Lead endocarditis may be associated with septic embolism, in which case the administration mode, type, and duration of antibiotic therapy must be adapted. However, diagnosis can be challenging: magnetic resonance imaging (MRI) cannot be performed in the vast majority of patients with cardiac implantable electronic devices (CIEDs). FDG PET/CT scanning has been proposed as a diagnostic tool for suspected CIED infection. METHODS: Thirty-five consecutive patients with lead endocarditis were prospectively studied. FDG PET/CT scanning was performed and analyzed blindly by experienced nuclear medicine physicians to assess for the presence of septic embolism 2 days before lead extraction. RESULTS: FDG PET/CT scanning identified septic emboli in 10 patients (29%): 7 with spondylodiscitis, 2 with septic pulmonary emboli, and 1 with an infected vascular prosthesis. Among the 7 patients with occult spondylodiscitis, 4 were asymptomatic, and 3 had back pain with negative CT imaging, MRI being contraindicated due to non MRI-compatible CIEDs. Antimicrobial therapy was adapted (double antibiotic therapy with good bone penetration) and prolonged. Among other important ancillary findings, 3 patients presented focal FDG uptake in the colon (1 adenocarcinoma, and 2 resected polyps) and 2 in the esophagus (both cases confirmed as neoplasia). CONCLUSIONS: This study emphasizes the potential utility of FDG PET/CT scanning as a diagnostic tool for septic emboli in patients with pacing lead endocarditis. This promising diagnostic tool may be integrated in the diagnostic algorithm of patients with lead endocarditis because diagnosis of septic embolisms has a direct and significant impact on the therapeutic care pathway.

Accuracy of Positron Emission Tomography as a Diagnostic Tool for Lead Endocarditis: Design of the Prospective Multicentre ENDOTEP Study.

Background: Rates of pacemaker implantation are steadily increasing and as patients are living longer, endovenous leads remain implanted for an extended period of time thereby increasing the risk of cardiac implantable electronic device (CIED) infection. Investigating fever of unknown origin in patients with implanted pacemakers can be challenging. Recently, 18F-fluorodeoxyglucose positron emission tomography/computerised tomography (18F-FDG-PET/CT) scanning has been used as a diagnostic tool for lead endocarditis in small studies. Objectives: ENDOTEP is a prospective and multicentre study designed to evaluate the accuracy of 18F-FDG-PET/CT scanning in the diagnosis of lead endocarditis. Methods: A total of 250 patients referred for pacemaker extraction due to suspicion of an infected device will be prospectively enrolled in six French regional centres for investigation and treatment of CIED infection. 18F-FDG-PET/CT scanning (index test) will be performed in each patient in the 48 hours preceding lead extraction. Bacteriological cultures (reference standard) will assess the presence of lead endocarditis, blind to 18F-FDG-PET/CT results. Enrolment started in June 2015 and is expected to end by June 2017. The primary objective will be to establish the sensitivity of the 18F-FDG-PET/CT scan for lead endocarditis. Secondary objectives will include other accuracy parameters, inter-observer agreement in the interpretation of 18F-FDG-PET/CT scanning, the influence of previous antibiotic therapy on 18F-FDG-PET/CT diagnostic accuracy and assessment of septic emboli associated to lead endocarditis. Conclusion: The ENDOTEP study will examine the ability of 18F-FDG-PET/CT scanning to avoid possible false-positive results, as is common using the current usual diagnostic strategy and may lead to unnecessary extraction of implants in patients with suspected lead infection.

Should white blood cell scan be replaced by (18)F-FDG PET-CT in the diagnosis of prosthetic vascular graft infection?

Diagnosis of prosthetic vascular graft infection (PVGI) is a clinical challenge requiring accurate diagnostic methods for their optimal management. A 65-year-old patient with suspected PVGI was explored by fluorodeoxyglucose positron emission tomography combined with computed tomography ((18)F-FDG PET-CT) for pretreatment staging. Standard imaging was unrevealing but PET images showed multiple foci with increased uptake suggesting prosthetic infection. While routine results from the diagnostic laboratory were negative, prosthesis sonication before standard culture revealed the same bacterium as a culture of preoperative lymphocele aspiration. (18)F-FDG PET-CT and preliminary sonication of the prosthetic graft could be very helpful in the diagnosis of PVGI especially for highlighting biofilm bacteria.

High performances of (18)F-fluorodeoxyglucose PET-CT in cardiac implantable device infections: A study of 40 patients.

BACKGROUND: Cardiovascular implantable electronic devices (CIED) infections are life-threatening complications. The diagnosis can be difficult to establish. Our purpose is to evaluate the diagnostic value of (18)F-FDG PET. METHODS: Forty patients who received work-up for suspected CIED infection were retrospectively included (group 1) and compared with 40 controls (group 2); CIED patients were referred for oncologic PET. PET-CT data were blindly assessed. Interpretation was based on visual analysis of both attenuation-corrected and non-corrected images and a semi-quantitative analysis was performed. The gold standard was bacteriological data of explanted devices or clinical follow-up for at least 1 year. RESULTS: Infection was present in 18 out of 40 patients of group 1. Sensitivity, specificity, positive predictive value, and negative predictive value of PET-CT were 83%, 95%, 94%, and 88%, respectively. Accuracy was 90%. PET-CT revealed the presence of additional pathological hypermetabolic foci in 28% of cases. PET-CT was negative at implanted devices in all patients of group 2. CONCLUSION: (18)F-FDG PET-CT is helpful in the work-up of suspected CIED infections. It is a potential tool to make the accurate diagnosis of CIED infection and to assess the extent of infection. The promising results in this indication need to be validated in a prospective multicenter study.

18F-FDG PET-CT in suspected prosthetic vascular graft infection.

BACKGROUND: Diagnosis of prosthetic vascular graft infections is a clinical challenge, and surgical therapy is associated with comorbidity. Therefore, accurate diagnostic methods are required for their optimal management. METHODS: A 61-year-old-patient presented with erysipelas of the right lower limb 7 months after receiving a hybrid femoropopliteal bypass composed of a saphenous vein distally and external supported polytetrafluoroethylene proximally. He had been first treated for suspicious of septic arterial thrombosis or false aneurysm with antibiotics. A computed tomography (CT) angiogram was performed to detect any potential infection of the bypass and to explore erysipelas. It revealed a subcutaneous infiltration and an infiltration of the right groin but no anastomotic pseudoaneurysm or thrombosis of the bypass. The 2-[18F]-fluoro-2-desoxy-d-glucose positron emission tomography (18F-FDG PET) evidenced a significant uptake of cutaneous and subcutaneous tissue but no uptake on the vascular prosthetic graft. Therefore, the bypass was considered as noninfected and antibiotics were continued for 3 months. A physical examination on antibiotic cessation revealed a nonerythematous thigh with a C-reactive protein level significantly decreased to 36 mg/L and a normal white blood cell count. A PET scan confirmed this clinical improvement as attested by a dramatically decreased uptake of cutaneous and subcutaneous tissues and still no uptake of the graft. CONCLUSIONS: In conclusion, this case highlights the role that 18F-FDG PET-CT may play in excluding suspected prosthetic graft infection, thanks to its high sensitivity and in avoiding needless revision surgery with subsequent comorbidities.