Real-Life Use of [68Ga]Ga-DOTANOC PET/CT in Confirmed and Suspected NETs from a Prospective 5-Year Electronic Archive at an ENETS Center of Excellence: More Than 2000 Scans in More Than 1500 Patients.

The recent introduction of novel treatments for advanced neuroendocrine tumors (NETs) and the well-established impact of clinical case discussion within dedicated multidisciplinary teams indicates the need to promote the centralization of rare diseases, such as NENs (neuroendocrine neoplasms). Data on the real-life use of and indications for [68Ga]Ga-DOTANOC PET/CT were collected from a prospective monocentric 5-year electronic archive including consecutive patients with confirmed and suspected NETs (September 2017 to May 2022). Overall, 2082 [68Ga]Ga-DOTANOC PET/CT scans (1685 confirmed NETs, 397 suspected NETs) were performed in 1537 patients. A high positivity rate was observed across different clinical settings (approximately 70%). Approximately 910/2082 scans were requested by the local oncology ward (851 confirmed NETs, 59 suspected NETs). The following observations were found: (i) the detection rate across all indications was 73.2% (higher for staging, peptide receptor radioligand therapy (PRRT) selection, and treatment response assessment); (ii) in suspected NETs, PET was more often positive when based on radiological findings. This systematic data collection in a high-volume diagnostic center represents a reliable cohort reflecting the global trends in the use of [68Ga]Ga-DOTANOC PET/CT for different clinical indications and primary tumor sites, but prompts the need for further multicenter data sharing in such a rare and slowly progressive disease setting.

[68Ga]Ga-DOTANOC Uptake at Pancreatic Head/Uncinate Process: Is It a Persistent Diagnostic Pitfall Over Time?

PURPOSE: [68Ga]Ga-DOTA-peptide uptake in the pancreatic head/uncinate process (UP) is a frequent PET/CT finding. Although mostly physiologic, it can represent a pitfall in PET/CT reading, especially when focal. An increased frequency of UP uptake has been reported in patients (pts) affected by diabetes mellitus (DM). The aim of the study is to describe the frequency of [68Ga]Ga-DOTANOC UP uptake to evaluate its variations over time and its possible correlation with DM. METHODS: In September 2017, a monocentric prospective observational electronic archive was initiated at our center to collect clinical and imaging data of pts undergoing [68Ga]Ga-DOTANOC PET/CT. Among the pts enrolled in the first 6 months (Sept 2017 to Feb 2018), those presenting [68Ga]Ga-DOTANOC PET/CT uptake at UP level were included. Pts with UP lesions already documented on CT/MRI or those that underwent surgical excision of UP before PET/CT were excluded from the analysis. [68Ga]Ga-DOTANOC UP uptake was classified as diffuse or focal and compared with the pattern observed in previous PET/CT scans performed at our center. An increased frequency of UP uptake was also correlated with the presence of DM. RESULTS: In the first 6 months, 253 pts were enrolled in the archive and 172 out of them were included in the analysis. UP increased uptake was frequently observed (77/172, 44.8%) and was mostly diffuse (62/77). In 75/172 pts (43.6%), previous [68Ga]Ga-DOTANOC PET/CT scans were available (overall 268 scans; number of previous PET per pt range: 1-20) and were retrospectively reviewed. Despite the fact that, in most pts, the uptake pattern was stable over time (54/75 pts, 72%), it changed in approximately one third of cases (21/75, 28%). Among DM pts (29/172), only 10/29 (34.4%) presented increased UP uptake. CONCLUSIONS: UP [68Ga]Ga-DOTANOC uptake is a frequent non-malignant finding (slightly higher than previously reported), mostly presenting with a diffuse pattern. However, contrary to previous reports, our data show that the pattern of uptake may vary over time in approximately one third of the cases and it is not more frequently observed in pts with DM.

Two birds with one stone: can [68Ga]Ga-DOTANOC PET/CT image quality be improved through BMI-adjusted injected activity without increasing acquisition times?

OBJECTIVES: To assess how patients' dependent parameters may affect [68Ga]Ga-DOTANOC image quality and to propose a theoretical body mass index (BMI)-adjusted injected activity (IA) scheme, to improve imaging of high weight patients. METHODS: Among patients prospectively enrolled (June-2019 and May-2020) in an Institutional Ethical Committee-approved electronic archive, we included those affected by primary gastro-entero-pancreatic (GEP) or lung neuroendocrine tumour and referred by our Institutional clinicians (excluding even minimal radiopharmaceutical extravasation, movement artefacts, renal insufficiency). All PET/CT images were acquired following EANM guidelines and rated for visual quality (1 = non-diagnostic, 2 = poor, 3 = moderate, 4 = good). Collected data included patient's body mass, height, BMI, age, IA (injected activity), IA/Kg (IAkg), IA/BMI (IABMI), liver SUVmean, liver SUVmax standard deviation, liver-signal-to-noise (LSNR), normalised_LSNR (LSNR_norm) and contrast-to-noise ratio (CNR) for positive scans and were compared to image rating (poor vs moderate/good). RESULTS: Overall, 77 patients were included. Rating concordance was high (agreement = 81.8%, Fleiss k score = 0.806). All patients' dependent parameters resulted significantly different between poor-rated and moderate/good-rated scans (IA: p = 0.006, IAkg: p =< 0.001, body weight: p =< 0.001, BMI: p =< 0.001, IABMI: p =< 0.001). Factors significantly associated with moderate/good rating were BMI (p =< 0.001), body weight (p =< 0.001), IABMI (p =< 0.001), IAkg (p = 0.001), IA (p = 0.003), LSNR_norm (p = 0.01). The BMI-based model presented the best predictive efficiency (81.82%). IABMI performance to differentiate moderate/good from poor rating resulted statistically significant (IA-AUC = 0.78; 95% CI: 0.68-0.89; cut-off value of 4.17 MBq*m2/kg, sensitivity = 81.1%, specificity = 66.7%). If BMI-adjusted IA (=4.17*BMI) would have been applied in this population, the median IA would have slightly inferior (-4.8%), despite a different IA in each patient. ADVANCES IN KNOWLEDGE: BMI resulted the best predictor of image quality. The proposed theoretical BMI-adjusted IA scheme (4.17*BMI) should yield images of better quality (especially in high-BMI patients) maintaining practical scanning times (3 min/bed).

Can Q.Clear reconstruction be used to improve [68 Ga]Ga-DOTANOC PET/CT image quality in overweight NEN patients?

AIM/INTRODUCTION: Digital PET/CT allows Q.Clear image reconstruction with different Beta (ß) levels. However, no definitive standard ß level for [68 Ga]Ga-DOTANOC PET/CT has been established yet. As patient's body mass index (BMI) can affect image quality, the aim of the study was to visually and semi-quantitatively assess different ß levels compared to standard OSEM in overweight patients. MATERIALS AND METHODS: Inclusion criteria: (1) patients with NEN included in a prospective CE-approved electronic archive; (2) [68 Ga]Ga-DOTANOC PET/CT performed on a digital tomograph between September2019/March2021; (3) BMI ≥ 25. Images were acquired following EANM guidelines and reconstructed with OSEM and Q.Clear with three ß levels (800, 1000, 1600). Scans were independently reviewed by three expert readers, unaware of clinical data, who independently chose the preferred ß level reconstruction for visual overall image quality. Semi-quantitative analysis was performed on each scan: SUVmax of the highest uptake lesion (SUVmax-T), liver background SUVmean (SUVmean-L), SUVmax-T/SUVmean-L, Signal-to-noise ratio for both liver (LSNR) and the highest uptake lesion (SNR-T), Contrast-to-noise ratio (CNR). RESULTS: Overall, 75 patients (median age: 63 years old [23-87]) were included: pre-obesity sub-group (25 ≤ BMI < 30, n = 50) and obesity sub-group (BMI ≥ 30, n = 25). PET/CT was positive for disease in 45/75 (60.0%) cases (14 obese and 31 pre-obese patients). Agreement among readers' visual rating was high (Fleiss κ = 0.88) and the ß1600 was preferred in most cases (in 96% of obese patients and in 53.3% of pre-obese cases). OSEM was considered visually equal to ß1600 in 44.7% of pre-obese cases and in 4% of obese patients. In a minority of pre-obese cases, OSEM was preferred (2%). In the whole population, CNR, SNR-T and LSNR were significantly different (p < 0.001) between OSEM and ß1600, conversely to SUVmean-L (not significant). These results were also confirmed when calculated separately for the pre-obesity and obesity sub-groups ß800 and ß1000 were always rated inferior. CONCLUSIONS: Q.Clear is a new technology for PET/CT image reconstruction that can be used to increase CNR and SNR-T, to subsequently optimise overall image quality as compared to standard OSEM. Our preliminary data on [68 Ga]Ga-DOTANOC PET/CT demonstrate that in overweight NEN patients, ß1600 is preferable over ß800 and ß1000. Further studies are warranted to validate these results in lesions of different anatomical region and size; moreover, currently employed interpretative PET positivity criteria should be adjusted to the new reconstruction method.

A [68Ga]Ga-DOTANOC PET/CT Radiomic Model for Non-Invasive Prediction of Tumour Grade in Pancreatic Neuroendocrine Tumours.

Predicting grade 1 (G1) and 2 (G2) primary pancreatic neuroendocrine tumour (panNET) is crucial to foresee panNET clinical behaviour. Fifty-one patients with G1-G2 primary panNET demonstrated by pre-surgical [68Ga]Ga-DOTANOC PET/CT and diagnostic conventional imaging were grouped according to the tumour grade assessment method: histology on the whole excised primary lesion (HS) or biopsy (BS). First-order and second-order radiomic features (RFs) were computed from SUV maps for the whole tumour volume on HS. The RFs showing the lowest p-values and the highest area under the curve (AUC) were selected. Three radiomic models were assessed: A (trained on HS, validated on BS), B (trained on BS, validated on HS), and C (using the cross-validation on the whole dataset). The second-order normalized homogeneity and entropy was the most effective RFs couple predicting G2 and G1. The best performance was achieved by model A (test AUC = 0.90, sensitivity = 0.88, specificity = 0.89), followed by model C (median test AUC = 0.87, sensitivity = 0.83, specificity = 0.82). Model B performed worse. Using HS to train a radiomic model leads to the best prediction, although a "hybrid" (HS+BS) population performs better than biopsy-only. The non-invasive prediction of panNET grading may be especially useful in lesions not amenable to biopsy while [68Ga]Ga-DOTANOC heterogeneity might recommend FDG PET/CT.

Overview and recent advances in PET/CT imaging in lymphoma and multiple myeloma.

Imaging in hematological diseases has evolved extensively over the past several decades. Positron emission tomography/computed tomography (PET/CT) with of 2-[18 F]-fluoro-2-deoxy-d-glucose ([18 F] FDG) is currently essential for accurate staging and for early and late therapy response assessment for all FDG-avid lymphoproliferative histologies. The widely adopted visual Deauville 5-point scale and Lugano Classification recommendations have recently standardized PET scans interpretation and improved lymphoma patient management. In addition [18 F] FDG-PET is routinely recommended for initial evaluation and treatment response assessment of Multiple Myeloma (MM) with significant contribution in risk-stratification and prognostication, although magnetic resonance imaging remains the Gold Standard for the assessment of bone marrow involvement. In this review, an overview of the role of [18 F] FDG-PET, in hematological malignancies is provided, particularly focusing on Hodgkin lymphoma (HL) and Diffuse Large B Cell Lymphoma (DLBCL), both in adult and pediatric populations, and MM, at each point of patient management. Potential alternative molecular imaging applications in this field, such as non-[18 F] FDG-tracers, whole body magnetic resonance imaging (WB-MRI), hybrid PET/MRI and emerging radiomics research are briefly presented.

Baseline total metabolic tumour volume on 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography-computed tomography as a promising biomarker in patients with advanced non-small cell lung cancer treated with first-line pembrolizumab.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have become the standard of care in the management of advanced non-small cell lung cancer (NSCLC). Nevertheless, only a small proportion of patients benefit from ICIs. The aim of the present study is to assess whether 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography-computed tomography ([18F]FDG-PET/CT)-derived parameters may be used as biomarkers in patients with advanced NSCLC receiving first-line pembrolizumab. MATERIALS AND METHODS: This is a monocentric retrospective cohort study including patients with advanced NSCLC (stage IV) and Programmed death-ligand 1 (PD-L1) expression ≥50% treated with pembrolizumab. A control group of patients treated with epidermal growth factor receptor (EGFR) inhibitors for EGFR-mutated NSCLC was also enrolled. Only patients with a positive [18F]18F-FDG PET/CT result within 60 days from treatment initiation were included.Total metabolic tumour volume (tMTV) was calculated for each lesion using a dedicated software (PET VCAR; GE Healthcare), which semiautomatically delineates the tumour's contours with a maximum standardised uptake value (SUVmax) threshold of 42% within the lesion. tMTV was obtained summing each lesion's MTV. Potential prognostic parameters for overall survival (OS) were analysed (tMTV, SUVmax, bone/liver metastasis, neutrophil:lymphocyte ratio ≥4, Eastern Cooperative Oncology Group performance status ≥2, lactate dehydrogenase above the upper limit of normal). RESULTS: Overall, 34 patients treated with first line-pembrolizumab and 40 patients treated with EGFR tyrosine kinase inhibitors were included. In the pembrolizumab group, the median follow-up was 20.3, while the median OS was 4.7 months (95% confidence interval [CI] = 0.3-9.1) for patients with tMTV ≥75 cm3 vs not reached (NR) for patients with tMTV <75 cm3 (95% CI = NR-NR; hazard ratio [HR] = 5.37; 95% CI = 1.72-16.77; p = 0.004). No difference was found in the control group (HR = 1.43; 95% CI = 0.61-3.34; p = 0.411). CONCLUSION: Our data suggest that tMTV ≥75cm3 can be used as a prognostic biomarker of poor outcomes in patients with PD-L1-high advanced NSCLC treated with first-line pembrolizumab. This information could be useful for the selection of patients who may require the addition of chemotherapy to pembrolizumab.

99mTc-Mebrofenin Hepatobiliary Scintigraphy Combined With SPECT/CT to Assess Liver Function in Heterotopic Segmental Liver Transplantation in the Splenic Fossa.

ABSTRACT: Recent studies have shown that the inclusion of a noninvasive and low-cost functional test such as hepatobiliary scintigraphy is considered more reliable than volume alone to predict posthepatectomy liver failure especially in light of new liver regeneration techniques. We herein reported the unique case of a 40-year-old man who underwent heterotopic liver transplantation of segments 2 and 3 in the splenic fossa after splenectomy for unresectable colorectal liver metastases. 99mTc-mebrofenin hepatobiliary scintigraphy combined with SPECT/CT was performed after liver transplantation to monitor graft function and regeneration before removal of the native liver.

Role of PET/CT and Therapy Management of Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show peculiar clinical and histomorphological features, with variable prognosis. In recent years, advances in knowledge regarding the pathophysiology and heterogeneous clinical presentation, as well as the availability of different diagnostic procedures for panNEN diagnosis and novel therapeutic options for patient clinical management, has led to the recognition of the need for an active multidisciplinary discussion for optimal patient care. Molecular imaging with positron emission tomography/computed tomography (PET/CT) has become indispensable for the management of panNENs. Several PET radiopharmaceuticals can be used to characterize either panNEN receptor expression or metabolism. The aim of this review is to offer an overview of all the currently used radiopharmaceuticals and of the new upcoming tracers for pancreatic neuroendocrine tumors (panNETs), and their clinical impact on therapy management. [68Ga]Ga-DOTA-peptide PET/CT (SSA-PET/CT) has high sensitivity, specificity, and accuracy and is recommended for the staging and restaging of any non-insulinoma well-differentiated panNEN cases to carry out detection of unknown primary tumor sites or early relapse and for evaluation of in vivo somatostatin receptors expression (SRE) to select patient candidates for peptide receptor radiometabolic treatment (PRRT) with 90Y or 177Lu and/or cold analogs. SSA-PET/CT also has a strong impact on clinical management, leading to a change in treatment in approximately a third of the cases. Its role for treatment response assessment is still under debate due to the lack of standardized criteria, even though some semiquantitative parameters seem to be able to predict response. [18F]FDG PET/CT generally shows low sensitivity in small growing and well-differentiated neuroendocrine tumors (NET; G1 and G2), while it is of utmost importance in the evaluation and management of high-grade NENs and also provides important prognostic information. When positive, [18F]FDG PET/CT impacts therapeutical management, indicating the need for a more aggressive treatment regime. Although FDG positivity does not exclude the patient from PRRT, several studies have demonstrated that it is certainly useful to predict response, even in this setting. The role of [18F]FDOPA for the study of panNET is limited by physiological uptake in the pancreas and is therefore not recommended. Moreover, it provides no information on SRE that has crucial clinical management relevance. Early acquisition of the abdomen and premedication with carbidopa may be useful to increase the accuracy, but further studies are needed to clarify its utility. GLP-1R agonists, such as exendin-4, are particularly useful for benign insulinoma detection, but their accuracy decreases in the case of malignant insulinomas. Being a whole-body imaging technique, exendin-PET/CT gives important preoperative information on tumor size and localization, which is fundamental for surgical planning as resection (enucleation of the lesion or partial pancreatic resection) is the only curative treatment. New upcoming tracers are under study, such as promising SSTR antagonists, which show a favorable biodistribution and higher tumor-to-background ratio that increases tumor detection, especially in the liver. [68Ga]pentixafor, an in vivo marker of CXCR4 expression associated with the behavior of more aggressive tumors, seems to only play a limited role in detecting well-differentiated NET since there is an inverse expression of SSTR2 and CXCR4 in G1 to G3 NETs with an elevation in CXCR4 and a decrease in SSTR2 expression with increasing grade. Other tracers, such as [68Ga]Ga-PSMA, [68Ga]Ga-DATA-TOC, [18F]SiTATE, and [18F]AlF-OC, are also under investigation.

PET imaging in testicular tumours.

PURPOSE OF REVIEW: Testicular cancer is rare, but its incidence is expected to rise. [18F] fluorodeoxyglucose ([18F]FDG) PET/computed tomography (CT) added role in testicular cancer management has been defined in a set of specific clinical settings. The current review focuses on recent advances in the employment of PET/CT in testicular cancer patients. RECENT FINDINGS: [18F]FDG PET/CT is not recommended for initial staging or for suspected testicular tumours. PET/CT role in testicular cancer management is mainly for the assessment of seminoma residual masses after therapy (>3 cm). Although [18F]FDG PET/CT has a very high negative predictive value, its positive predictive value varies across studies: appropriate PET/CT scheduling after therapy and a careful history are mandatory for accurate interpretation. Interim PET/CT could prove valuable to spare subsequent chemotherapy cycles in patients already in remission, reducing related toxicity. The role of [18F]FDG in nonseminoma tumours is hampered by the low sensitivity in teratoma. SUMMARY: [18F]FDG PET/CT is currently used for the assessment of seminoma residual masses (>3 cm) after therapy. A negative PET could also spare unnecessary further chemotherapy cycles in responding patients, reducing toxicity. Although rare, testicular secondary lesions can be detected with non[18F]FDG tracers when PET/CT is performed for other primary tumours.

Impact of the COVID-19 pandemic in nuclear medicine departments: preliminary report of the first international survey.

PURPOSE: Coronavirus disease-19 (COVID-19) pandemic is challenging the availability of hospital resources worldwide. The Young Group of the Italian Association of Nuclear Medicine (AIMN) developed the first international survey to evaluate the impact of COVID-19 in nuclear medicine (NM). The aim of this study was to perform a preliminary report of the ongoing survey. METHODS: A questionnaire of thirty questions was prepared for all NM professionals addressing three main issues: (1) new scheduling praxes for NM diagnostic and therapeutic procedures, (2) assistance of patients with diagnosed or suspected COVID-19, and (3) prevention of COVID-19 spreading in the departments. An invitation to the survey was sent to the corresponding authors of NM scientific papers indexed in SCOPUS in 2019. Personal data were analysed per individual responder. Organisation data were evaluated per single department. RESULTS: Two-hundred and ninety-six individual responders from 220 departments were evaluated. Most of the responders were from Europe (199/296, 67%). Approximately, all departments already changed their scheduling praxes due to the pandemic (213/220, 97%). In most departments, scheduled diagnostic and therapeutic procedures were allowed but quantitatively reduced (112/220, 51%). A significant reduction of diagnostic and therapeutic procedures (more than 20%) affected 198/220 (90%) and 158/220 (72%) departments, respectively. Incidental COVID-19 signs in NM exams occurred in 106/220 departments (48%). Few departments were closed or shifted to assist patients with COVID-19 (36/220, 16%). Most of the responders thought that pandemic would not permanently change the work of NM departments in the future (189/296, 64%). CONCLUSIONS: According to this preliminary report of the first international survey, COVID-19 heavily impacted NM departments and professionals. New praxes for NM procedures, assistance, and prevention of COVID-19 have been applied during the pandemic.

Theragnostic Use of Radiolabelled Dota-Peptides in Meningioma: From Clinical Demand to Future Applications.

Meningiomas account for approximately 30% of all new diagnoses of intracranial masses. The 2016 World Health Organization's (WHO) classification currently represents the clinical standard for meningioma's grading and prognostic stratification. However, watchful waiting is frequently the chosen treatment option, although this means the absence of a certain histological diagnosis. Consequently, MRI (or less frequently CT) brain imaging currently represents the unique available tool to define diagnosis, grading, and treatment planning in many cases. Nonetheless, these neuroimaging modalities show some limitations, particularly in the evaluation of skull base lesions. The emerging evidence supporting the use of radiolabelled somatostatin receptor analogues (such as dota-peptides) to provide molecular imaging of meningiomas might at least partially overcome these limitations. Moreover, their potential therapeutic usage might enrich the current clinical offering for these patients. Starting from the strengths and weaknesses of structural and functional neuroimaging in meningiomas, in the present article we systematically reviewed the published studies regarding the use of radiolabelled dota-peptides in surgery and radiotherapy planning, in the restaging of treated patients, as well as in peptide-receptor radionuclide therapy of meningioma.