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Purpose: The aim of the present study is to assess if 2-[18F]FDG uptake can be enhanced by subjecting human ADK-LPA derived cell lines and murine models carrying ADK-LPA to a low-glucose intake dietary regimen so to potentially ameliorate the CT/PET sensitivity in human patients. Methods: A dietary regimen envisaging a low glucose uptake (ketogenic diet) and a normal diet were applied to a human ADK-LPA derived cell line (NCI-H358) and to other two lung carcinoma cell lines (A549 and NCI-H1299) for comparison purposes. Cells were afterwards incubated with 2-[18F]FDG. Moreover, the correspondent regimens were enforced on murine models carrying ADK-LPA xenografts to evaluate the influence of the diet on the 2-[18F]FDG biodistribution and visualization upon injection. Results: As expected, when incubated with glucose-rich medium, NCI-H358 (ADK-LPA) cells have a really low [18F]FDG uptake (up to 4-fold less) compared to A549 and NCI- H1299 cells. On the other hand, when a glucose-depleted medium is used, a significantly enhanced uptake in NCI-H358 cells respect to the other two lines (up to 10-fold higher after 5 days) was obtained. In the PET/CT images, tumors are clearly better visualized in mice subjected to ketogenic diet respect to control group already after 3 days. Conclusion: The study attested how 2-[18F]FDG uptake in a low glucose dependent tumor, usually not detected by PET/CT, can be controlled in vitro and in murine models by a dietary regimen. The outputs of this study open the way to a possible method to improve the [18F]FDG-PET/CT performances in the detection of ADK-LPA thus laying the foundations of a possible future application in humans.

Abstract: Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. Study registration: This protocol was registered in clinicaltriasl.gov (NCT04282083).

The timing of individual neuronal spikes is essential for biological brains to make fast responses to sensory stimuli. However, conventional artificial neural networks lack the intrinsic temporal coding ability present in biological networks. We propose a spiking neural network model that encodes information in the relative timing of individual spikes. In classification tasks, the output of the network is indicated by the first neuron to spike in the output layer. This temporal coding scheme allows the supervised training of the network with backpropagation, using locally exact derivatives of the postsynaptic spike times with respect to presynaptic spike times. The network operates using a biologically plausible synaptic transfer function. In addition, we use trainable pulses that provide bias, add flexibility during training, and exploit the decayed part of the synaptic function. We show that such networks can be successfully trained on multiple data sets encoded in time, including MNIST. Our model outperforms comparable spiking models on MNIST and achieves similar quality to fully connected conventional networks with the same architecture. The spiking network spontaneously discovers two operating modes, mirroring the accuracy-speed tradeoff observed in human decision-making: a highly accurate but slow regime, and a fast but slightly lower accuracy regime. These results demonstrate the computational power of spiking networks with biological characteristics that encode information in the timing of individual neurons. By studying temporal coding in spiking networks, we aim to create building blocks toward energy-efficient, state-based biologically inspired neural architectures. We provide open-source code for the model.

The endothelium, once considered a mere selectively permeable barrier between the bloodstream and the outer vascular wall, is now recognized to be a crucial homeostatic organ, fundamental for the regulation [...]

Background: We aimed to test whether the prognostic value of 18 F‐Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) in metastatic castration-resistant prostate cancer (mCRPC) extends to the estimation of systemic treatment response duration. Methods: mCRPC patients submitted to FDG-PET/CT in four Italian centers from 2005 to 2020 were retrospectively enrolled. Clinical and biochemical data at the time of imaging were collected, and SUV max of the hottest lesion, total metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. The correlation between PET- and biochemical-derived parameters with Overall Survival (OS) was analysed. The prediction of treatment response duration was assessed in the subgroup submitted to FDG-PET/CT in the six months preceding Chemotherapy (namely Docetaxel or Cabazitaxel, 24 patients) or Androgen-Receptor Targeted Agents (ARTA, namely Abiraterone or Enzalutamide, 20 patients) administration. Results: We enrolled 114 mCRPC patients followed-up for a median interval lasting 15 months. While at univariate analysis, prostate-specific antigen (PSA), Alkaline Phosphatase (ALP), MTV, and TLG were associated with OS, at the multivariate Cox regression analysis, the sole MTV could independently predict OS (p< 0.0001). In the subgroup submitted to FDG-PET/CT before the systemic treatment initiation, PSA and TLG could also predict treatment response duration independently (p< 0.05). Of note, while PSA could not indicate the best treatment choice, lower TLG was associated with higher success rates for ARTA but had no impact on chemotherapy efficacy. Conclusions: FDG-PET/CT’s prognostic value extends to predicting treatment response duration in mCRPC, thus potentially guiding the systemic treatment selection.

Purpose: Aim of the present review is to analyze the most relevant achievements of peptide receptor radionuclide therapy (PRRT) in neuroendocrine neoplasms (NENs) management, focusing on treatment efficacy as well as toxicity and taking into account the innovative applications and future perspectives. Methods: A comprehensive literature review of PubMed/Medline (last updated January 2021) was performed using a combination of the following keywords: PRRT, NEN/NET treatment, somatostatin analogues, PET/CT [68Ga]Ga-DOTA-peptides (DOTATATE, DOTATOC, DOTANOC), [18F]FDG. Case reports, editorials, letters to the editor and articles not specifically addressing PRRT achievements were excluded. Only papers in English were considered. Results: Published data showed that PRRT has been increasingly used for treatment of well-differentiated neuroendocrine tumours (NETs). Preliminary results from early studies were difficult to compare due to different treatment regimens in often small and heterogeneous patients’ populations. Recently, the regulatory agencies approved [177Lu]Lu-DOTA-TATE for treatment of well-differentiated gastro-entero-pancreatic neuroendocrine tumours G1-G2 (GEP-NET). Patients treated with PRRT show good response rates (range 66–95% considering total objective response and stable disease). Regarding toxicity, a significant reduction of renal absorbed dose (ranging from 9 to 53%) has been reported using kidney protection strategies. Moreover, the incidence of haematological long-term toxicity has been reported in many studies but toxicity is mild and transient in most patients while severe toxicity, such as acute leukemia (AL) and myelodysplastic syndrome (MDS), were reported in less than 3% of patients. However, several issues are still under debate including dose schemes personalization, selection of eligible patients, evaluation of treatment response and treatment sequencing. Conclusion: PRRT is now recognized as an effective treatment strategy for well-differentiated SSTR-positive NETs with a very high disease control and overall limited toxicity. Further optimization of PRRT employment is warranted to further increase efficacy and reduce toxicity.

Aim: The diagnosis, severity and extent of a sterile inflammation or a septic infection could be challenging since there is not one single test able to achieve an accurate diagnosis. The clinical use of 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) imaging in the assessment of inflammation and infection is increasing worldwide. The purpose of this paper is to achieve an Italian consensus document on [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases, such as osteomyelitis (OM), prosthetic joint infections (PJI), infective endocarditis (IE), prosthetic valve endocarditis (PVE), cardiac implantable electronic device infections (CIEDI), systemic and cardiac sarcoidosis (SS/CS), diabetic foot (DF), fungal infections (FI), tuberculosis (TBC), fever and inflammation of unknown origin (FUO/IUO), pediatric infections (PI), inflammatory bowel diseases (IBD), spine infections (SI), vascular graft infections (VGI), large vessel vasculitis (LVV), retroperitoneal fibrosis (RF) and COVID-19 infections. Methods: In September 2020, the inflammatory and infectious diseases focus group (IIFG) of the Italian Association of Nuclear Medicine (AIMN) proposed to realize a procedural paper about the clinical applications of [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases. The project was carried out thanks to the collaboration of 13 Italian nuclear medicine centers, with a consolidate experience in this field. With the endorsement of AIMN, IIFG contacted each center, and the pediatric diseases focus group (PDFC). IIFG provided for each team involved, a draft with essential information regarding the execution of [18F]FDG PET/CT or PET/MRI scan (i.e., indications, patient preparation, standard or specific acquisition modalities, interpretation criteria, reporting methods, pitfalls and artifacts), by limiting the literature research to the last 20 years. Moreover, some clinical cases were required from each center, to underline the teaching points. Time for the collection of each report was from October to December 2020. Results: Overall, we summarized 291 scientific papers and guidelines published between 1998 and 2021. Papers were divided in several sub-topics and summarized in the following paragraphs: clinical indications, image interpretation criteria, future perspectivess and new trends (for each single disease), while patient preparation, image acquisition, possible pitfalls and reporting modalities were described afterwards. Moreover, a specific section was dedicated to pediatric and PET/MRI indications. A collection of images was described for each indication. Conclusions: Currently, [18F]FDG PET/CT in oncology is globally accepted and standardized in main diagnostic algorithms for neoplasms. In recent years, the ever-closer collaboration among different European associations has tried to overcome the absence of a standardization also in the field of inflammation and infections. The collaboration of several nuclear medicine centers with a long experience in this field, as well as among different AIMN focus groups represents a further attempt in this direction. We hope that this document will be the basis for a “common nuclear physicians’ language” throughout all the country.

ABSTRACTBackgroundSomatostatin receptor ligands including octreotide LAR are first-line therapy in locally advanced or metastatic NETs that are nonresectable and well differentiated and are recommended as first-line therapy in functioning and in G1/low G2 nonfunctioning NETs. However, several questions remain that are not adequately addressed in current guidelines regarding its use in clinical scenarios in which the tumor progresses. These include use of nonconventional doses or schedules of octreotide LAR in tumors with hormonal symptoms or showing clinical-radiological progression, administration in combination with everolimus, peptide receptor radionuclide therapy, and chemotherapy, following first-line treatment with octreotide LAR.MethodsAn expert panel was gathered to obtain consensus using Delphi methodology on a series of statements regarding further administration of octreotide LAR after its use in first-line therapy in these settings in patients who experience disease progression.ResultsConsensus was reached for 8 of the 10 statements proposed in the above clinical scenarios; consensus was not achieved for two statements.ConclusionsThe present statements aim to fill current gaps in treatment guidelines by providing recommendations based on expert consensus in clinical settings in which patients progress following first-line therapy with octreotide LAR.

The aim of this project was to register, in a liquid chromatography–mass spectrometry-based untargeted single-batch analysis, the metabolome of 11 single-cultivar, single-vintage Italian red wines (Aglianico, Cannonau, Corvina, Montepulciano, Nebbiolo, Nerello, Primitivo, Raboso, Sagrantino, Sangiovese, and Teroldego) from 12 regions across Italy, each one produced in their terroirs under ad hoclegal frameworks to guarantee their quality and origin. The data provided indications regarding the similarity between the cultivars and highlighted a rich list of putative biomarkers of origin wines (pBOWs) characterizing each individual cultivar–terroir combination, where Primitivo, Teroldego, and Nebbiolo had the maximum number of unique pBOWs. The pBOWs included anthocyanins (Teroldego), flavanols (Aglianico, Sangiovese, Nerello, and Nebbiolo), amino acids and N-containing metabolites (Primitivo), hydroxycinnamates (Cannonau), and flavonols (Sangiovese). The raw data generated in this study are publicly available and, therefore, accessible and reusable as a baseline data set for future investigations.

Ectopic ACTH secretion (EAS) is mostly secondary to thoracic/abdominal neuroendocrine tumours (NETs) or small cell-lung carcinoma (SCLC). We studied the diagnostic accuracy of CT with 68Ga-Dota derivatives (68Ga-SSTR) PET in localizing ACTH-secreting tumor in patients with EAS.68Ga-SSTR-PET/CT was performed and compared with the nearest enhanced CT in 18 cases (16 primary and 2 recurrent neoplasms). Unspecific, indeterminate and false-positive uptakes were assessed using conventional imaging, follow-up or histology.We diagnosed 13 thoracic (9 primary and 2 recurrent bronchial carcinoids, 2 SCLCs) and 1 abdominal (pancreatic NET) tumors. Eight ACTH-secreting tumors were promptly identified at EAS diagnosis (’overt’, four pulmonary carcinoids with two recurrences and two SCLC); six EAS have been discovered during the subsequent follow-up (’covert’, five bronchial carcinoids and one pancreatic NET). At the time of EAS diagnosis, imaging was able to correctly detect the ACTH-secreting tumour in 8/18 cases (6 new diagnosis and 2 recurrences). During the follow-up, six out of initially ten ‘occult’ cases became ‘covert’. At last available follow-up, CT and 68Ga-SSTR-PET/CT were able to diagnose 11/18 and 12/18 ACTH-secreting tumours, respectively (11/14 and 12/14 considering only overt and covert cases, respectively). Four cases have never been localized by conventional or nuclear imaging (’occult EAS’), despite an average follow-up of 5 years.The 68Ga-SSTR-PET/CT is useful in localizing EAS, especially to enhance positive prediction of the suggestive CT lesions and to detect occult neoplasms.

Introduction: In patients suitable for radical chemoradiotherapy for lung cancer, 18F-FDGPET/ CT is a proposed management to improve the accuracy of high dose radiotherapy. However, there is a high rate of locoregional failure in patients with locally advanced non-small cell lung cancer (NSCLC), probably due to the fact that standard dosing may not be effective in all patients. The aim of the present review was to address some criticisms associated with the radiotherapy image-guided in NSCLC. Materials and Methods: A systematic literature search was conducted. Only published articles that met the following criteria were included: articles, only original papers, radiopharmaceutical ([18F]FDG and any tracer other than [18F]FDG), target, only specific for lung cancer radiotherapy planning, and experimental design (eventually “in vitro” studies were excluded). Peer-reviewed indexed journals, regardless of publication status (published, ahead of print, in press, etc.) were included. Reviews, case reports, abstracts, editorials, poster presentations, and publications in languages other than English were excluded. The decision to include or exclude an article was made by consensus and any disagreement was resolved through discussion. Results: Hundred eligible full-text articles were assessed. Diverse information is now available in the literature about the role of FDG and new alternative radiopharmaceuticals for the planning of radiotherapy in NSCLC. In particular, the role of alternative technologies for the segmentation of FDG uptake is essential, although indeterminate for RT planning. The pros and cons of the available techniques have been extensively reported. Conclusion: PET/CT has a central place in the planning of radiotherapy for lung cancer and, in particular, for NSCLC assuming a substantial role in the delineation of tumor volume. The development of new radiopharmaceuticals can help overcome the problems related to the disadvantage of FDG to accumulate also in activated inflammatory cells, thus improving tumor characterization and providing new prognostic biomarkers.

Background:Primary mediastinal B-cell lymphoma (PMBCL) is clinically and biologically distinct from other types of aggressive lymphoma, it is characterized by a bulky mediastinal mass and most commonly occurs in women between 30 and 40 years of age. Although consolidation radiotherapy (RT) has yielded extremely positive outcomes in PMBCL, it carries a higher risk of long-term complications. Consequently, there has been an ongoing debate regarding the necessity of RT in patients responding to frontline immunochemotherapy.

Both total metabolic tumor volume (TMTV), computed on baseline positron emission tomography (PET), and end of induction (EOI) PET are imaging biomarkers showing promise for early risk stratification in patients with high-tumor-burden follicular lymphoma. A model was built incorporating these 2 factors in 159 patients from three prospective trials: 2 Lymphoma Study Association (LYSA) studies and 1 Fondazione Italiana Linfomi (FIL) trial. Median follow up was 64 months. High TMTV (>510 cm3) and positive EOI PET were independent, significant risk factors for progression. Their combination stratified the population into 3 risk groups: patients with no risk factors (n = 102; 64%) had a 5-year progression-free survival (PFS) of 67% vs 33% (hazard ratio [HR], 2.9; 95% confidence interval [CI], 1.8-4.9) for patients with 1 risk factor (n = 44; 27%) and only 23% (HR, 4.6; 95% CI, 2.3-9.2) for patients with both risk factors (n = 13; 8%). 2-year PFS was respectively 90% vs 61% (HR, 4.8; 95% CI, 2.2-10.4) and 46% (HR, 8.1; 95%CI, 3.1-21.3). This model enhances the prognostic value of PET staging and response assessment, identifying a subset of patients with a very high risk of progression and early treatment failure at 2 years.

We tested baseline positron emission tomography (PET)/computed tomography (CT) as a measure of total tumor burden to better identify high-risk patients with early-stage Hodgkin lymphoma (HL). Patients with stage I-II HL enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET and interim PET (iPET2) after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine were included. Total metabolic tumor volume (TMTV) was measured on baseline PET. iPET2 findings were reported negative (DS1-3) or positive (DS4-5) with the Deauville scale (DS). The prognostic value of TMTV was evaluated and compared with baseline characteristics, staging classifications, and iPET2. A total of 258 patients were eligible: 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 progression-free survival (PFS) and 12 overall survival (OS) events. TMTV was a prognosticator of PFS (P < .0001) and OS (P = .0001), with 86% and 84% specificity, respectively. Five-year PFS and OS were 71% and 83% in the high-TMTV (>147 cm3) group (n = 46), respectively, vs 92% and 98% in the low-TMTV group (≤147 cm3). In multivariable analysis including iPET2, TMTV was the only baseline prognosticator compared with the current staging systems proposed by the European Organization for Research and Treatment of Cancer/Groupe d’Etude des Lymphomes de l’Adulte, German Hodgkin Study Group, or National Comprehensive Cancer Network. TMTV and iPET2 were independently prognostic and, combined, identified 4 risk groups: low (TMTV≤147+DS1-3; 5-year PFS, 95%), low-intermediate (TMTV>147+DS1-3; 5-year PFS, 81.6%), high-intermediate (TMTV≤147+DS4-5; 5-year PFS, 50%), and high (TMTV>147+DS4-5; 5-year PFS, 25%). TMTV improves baseline risk stratification of patients with early-stage HL compared with current staging systems and the predictive value of early PET response as well.

The M.O.S.CA.TI. (Metastases of the Skeleton from CArcinoma of the ThyroId) is a multicenter, retrospective study investigating the real-life outcome and management of bone metastases (BM) in 143 patients (63 M, 80 F; median age 64 years, range 11–87) with differentiated thyroid carcinoma (DTC). Radio-active iodine (RAI) treatment was performed in 131 patients (91.6%), surgical approach and/or external radiotherapy in 68 patients (47.6%), and anti-resorptive bone-active drugs in 32 patients (22.4%; in 31 zoledronate and in one denosumab). At the start of treatment, 24 patients (75.0%) receiving anti-resorptive bone-active drugs had at least one clinical skeletal-related event (SRE) (p < 0.001). One or more clinical SREs (pathological fractures and/or malignant hypercalcemia and/or spinal cord compression) developed in 53 patients (37.1%). Development of SREs was significantly associated with metachronous BM (hazard ratio (HR) 2.04; p = 0.04), localization of BM to cervical spine (HR 3.89; p = 0.01), and lack of avid RAI uptake (HR 2.66; p = 0.02). Thirty-nine patients (27.3%) died in correlation with development of SREs (HR 6.97; p = 0.006) and localization of BM to the hip (HR 3.86; p = 0.02). Moreover, overall mortality was significantly decreased by RAI therapy (HR 0.10; p = 0.02), whereas no significant effects were induced by bone-active drugs (p = 0.36), external radiotherapy (p = 0.54), and surgery (p = 0.43) of BM. SREs are very frequent in BM from DTC and they impact patient survival. In the real life, the use of bone-active drugs is currently limited to zoledronate in patients with pre-existing SREs. In this clinical setting, RAI therapy, but not zoledronate, decreased mortality.

Peptide receptor radionuclide therapy (PRRT) is a molecular-targeted therapy in which a somatostatin analogue (a small peptide) is coupled with a radioligand so that the radiation dose is selectively administered to somatostatin receptor–expressing metastasized neuroendocrine tumors, particularly gastroenteropancreatic. Reported toxicities include myelotoxicity and nephrotoxicity, the latter manifesting as decreased kidney function, often developing months to years after treatment completion. We present a case of PRRT-induced kidney toxicity manifesting as a severe Gitelman-like tubulopathy with preserved kidney function. Because profound hypokalemia and hypocalcemia can lead to life-threatening arrhythmias, we highlight the necessity for careful monitoring of serum and urine electrolytes in patients receiving PRRT.

To assess the findings of contrast‐enhanced ultrasound (CEUS) of carotid arteries in patients with large vessel vasculitis (LVV) and to compare them with those observed using 18F‐fluorodeoxyglucose–positron emission tomography (18FDG‐PET). A total of 31 consecutive patients with LVV (14 with Takayasu arteritis, 17 with giant cell arteritis with large vessel involvement) underwent both PET/computed tomography and carotid artery color Doppler ultrasound (CDUS) for a total of 35 combined assessments. Right carotid artery CEUS was performed after CDUS in all assessments. Kerr's criteria, a complete clinical examination, and acute phase reactants were simultaneously evaluated. The intensity of vascular uptake and vascularization of the carotid artery wall were compared. Ten 18F‐FDG/PET scans showed active vascular 18F‐FDG uptake (visual grade ≥2) in the right carotid artery. CEUS demonstrated severe vascularization (grade 2) within the right carotid artery wall in 12 examinations. The carotid CEUS vascularization grade significantly correlated with vascular 18F‐FDG uptake (P< 0.001) and maximum standardized uptake value (SUV) in the right carotid artery/mean SUV in the superior vena cava (P= 0.001). When active vascular 18F‐FDG uptake (≥2) was considered the gold standard for defining vascular inflammation, carotid CEUS had a sensitivity of 100% (95% confidence interval [95% CI] 65–100) and a specificity of 92% (95% CI 72–99). The positive likelihood ratio was 12.5 (95% CI 3.3–47.2). Severe vascularization at CEUS and active vascular 18F‐FDG uptake were significantly more frequent in active disease according to Kerr's criteria compared to inactive (P= 0.001 and P= 0.002, respectively). Carotid CEUS vascularization grade and the grade of vascular inflammation on 18F‐FDG‐PET were correlated in patients with LVV.

The role of radiolabeled choline (Cho) in patients with biochemical recurrence after radical treatment for prostate cancer (PCa) is well established. Its widespread clinical use has prompted the depiction of incidentalomas, unusual sites of metastatic lesions, as well as false positive and negative cases. We reported a series of patients affected by biochemical recurrence of PCa imaged by [18F]Cho positron emission tomography/computed tomography (PET/CT) which resulted suspected for a second malignancy. [18F]Cho PET/CT was performed in patients with biochemical PCa recurrence. From an internal clinical database we identified patients in which PET/CT resulted suspected for a second malignancy. A second malignancy was suspected in presence of “unusual” site of [18F]Cho uptake not consistent with clinical-instrumental history. Histology was used as reference standard for final diagnosis. Seven PCa patients (76 years, 71–84 years) with the suspicion of a second tumor based on [18F]Cho PET/CT findings were identified. Mean value of PSA at the time of [18F]Cho PET/CT was 2,37 ng/mL. The median time between PCa diagnosis and PET/CT was 6 years (range 0–14 years). In two cases history of a second malignancy (lung cancer and cutaneous basocellular carcinoma) was known (diagnosed 12 and 6 years after PCa, respectively). PET/CT identified 13 sites of [18F]Cho uptake (lung = 5, lymph node = 7, bone = 1). Final diagnosis was consistent with lung cancer in 5/7 cases (first diagnosis = 4/5, recurrence = 1/5), colorectal cancer and nodal metastases from melanoma in 1 case each. Although the clinical usefulness of Cho PET/CT for detecting cancer lesions other than prostate origin is known, for those patients who undergo this examination according to indication, the diagnosis of a second tumor has a significant impact on their therapeutic management.

Identification of patient sub-groups with smoldering multiple myeloma (SMM) at high risk of progression to active disease (MM) is an important goal. 18F-FDG PET/CT (positron emission tomography (PET) integrated with computed tomography (PET/CT) using glucose labelled with the positron-emitting radionuclide 18F) allows for assessing early skeletal involvement. Identification of osteolytic lesions by this technique has recently been incorporated into the updated International Myeloma Working Group criteria for MM diagnosis. However, no data are available regarding the impact of focal lesions (FLs) without underlying osteolysis on time to progression (TTP) to MM. We hence prospectively studied a cohort of 120 SMM patients with PET/CT. PET/CT was positive in 16% of patients (1 FL: 8, 2 FLs: 3, >3 FLs: 6, diffuse bone marrow involvement: 2). With a median follow-up of 2.2 years, 38% of patients progressed to MM, in a median time of 4 years, including 21% with skeletal involvement. The risk of progression of those with positive PET/CT was 3.00 (95% confidence interval 1.58–5.69, P=0.001), with a median TTP of 1.1 versus 4.5 years for PET/CT-negative patients. The probability of progression within 2 years was 58% for positive versus 33% for negative patients. In conclusion, PET/CT positivity significantly increased the risk of progression of SMM to MM. PET/CT could become a new tool to define high-risk SMM.

In this work an overview of the local motion planning and dynamic perception framework within the V-Charge project is presented. This framework enables the V-Charge car to autonomously navigate in dynamic mixed-traffic scenarios. Other traffic participants are detected, classified and tracked from a combination of stereo and wide-angle monocular cameras. Predictions of their future movements are generated utilizing infrastructure information. Safe motion plans are acquired with a system-compliant sampling-based local motion planner. We show the navigation performance of this vision-only autonomous vehicle in both simulation and real-world experiments.

Most lymphoma types are fluorodeoxyglucose positron emission tomography (FDG-PET) positive, and FDG-PET/computed tomography (CT) is used routinely in staging and treatment evaluation of lymphomas. PET/CT imaging is important for contouring of the target for radiotherapy and changes the radiation volumes significantly compared with radiotherapy planning based on CT alone. Modern advanced imaging techniques with image fusion and inspiration breath hold have enabled further refinements of radiotherapy for lymphoma, reducing the risks of long-term side effects while maintaining the high cure rate for these diseases.

The use of germanium-68 (68Ge)gallium-68 (68Ga) generators is still limited when compared with the 99Mo99mTc counterpart, mainly because of the absence of commercial kits and a kit-based method for preparing 68Ga-labelled radiopharmaceuticals in a reliable way. The present study aimed to develop and optimize a reliable direct labelling of DOTATOC with 68Ga through a kit-based approach.

Pulmonary neuroendocrine tumors (pNETs) have distinct pathologic characteristics. Typical carcinoids are indolent neoplasms with a good prognosis, whereas atypical carcinoids have a less indolent behavior. Both are optimally treated with complete surgical excision. More aggressive pNETs often present with local invasion, thoracic lymph nodal metastases, and distant spread. Patients may not be candidates for surgical resection and are treated with chemotherapy and/or radiation therapy. This article examines the potential role of functional imaging evaluation using 18F FDG and somatostatin analogues labeled with 68Ga DOTA-peptides in well-differentiated pNETs with particular attention to clinical and surgical implications.

Hemodialysis is essential for patients with renal failure, and iodine-131 (131I) administration is the standard of care in thyroid carcinoma treatment. Although the need for hemodialysis during 131I treatment is very rare, it raises some concerns due to the involvement of personnel not exposed to radiation and to the contamination of devices used for other patients. In this paper, a radioprotection protocol to perform hemodialysis safely on patients during 131I treatment has been presented.

In this study the ability of the droplet evaporation method (DEM) to discriminate between organic and biodynamic Sangiovese red wines was studied for the first time. The relationship between the sizing-parameters and shape-descriptors of the crystal structures and the chemical parameters of wines was evaluated, and the most significant correlations were found between the intensity of red color of wines with circularity (r= 0.90) and solidity (r= 0.94). Moreover the shape-descriptors allowed a discrimination between the organic and biodynamic Sangiovese red wines based on two kinds of structures: (i) needle-like and (ii) flower-like forms.

Background:18F-FDG-PET/CT is currently the standard technique to define imaging-minimal residual disease (MRD) in multiple myeloma (MM) patients. A joint analysis of 2 prospective randomized trials in newly diagnosed transplant-eligible MM (NDTEMM) patients applied for the first time the Deauville Scores (DS) to focal lesions (FS) and bone marrow uptake (BMS) showing the liver background (DS < 4) as the best cut-off to define PET/CT negativity after therapy and complete metabolic response (CMR) (Zamagni et al, ASH 2018). Validation of this new standardized criteria in an independent prospective series of NDTEMM patients is highly required. Imaging-PET/CT MRD also showed to be complementary to Multiparameter Flow Cytometry (MFC) in predicting patient’s outcomes (Moreau P, JCO2017). In this analysis, we aimed at confirming the applicability and validity of DS criteria to define PET/CT CMR and showing their impact on patient’s outcomes in the multicenter phase II randomized FORTE trial for NDTEMM patients. We also looked at the complementarity with BM techniques, especially MFC.

The treatment of tumours expressing somatostatin receptors with yttrium-90 (90Y)-labelled and lutetium-177 (177Lu)-labelled somatostatin analogues is one of the most interesting therapeutic approaches adopted in nuclear medicine in recent years. However, the process of synthesis and fractionation of these radiopharmaceuticals is still mainly carried out manually despite the high radiation exposure to the operators and the need to comply with good manufacturing practices. In this study a semiautomatic synthesizer automatic dose dispenser (ADD-2) using only disposable syringes and vials has been presented.

Biocytin analogues labelled with indium-111, yttrium-90 and lutetium-177 have shown their effectiveness in the imaging of infectionsinflammation in patients with osteomyelitis and function as efficient tools in pretargeted antibody-guided radioimmunotherapy. In this study, the labelling of a biocytin analogue coupled with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), namely, r-BHD, with gallium-68 (68Ga) was optimized, and the quality and stability of the preparations were assessed for clinical use.

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are inflammatory diseases that typically affect white individuals >50 years. Women are affected ~2–3 times more often than men. PMR and GCA occur together more frequently than expected by chance. The main symptoms of PMR are pain and stiffness in the shoulders, and often in the neck and pelvic girdle. Imaging studies reveal inflammation of joints and bursae of the affected areas. GCA is a large-vessel and medium-vessel arteritis predominantly involving the branches of the aortic arch. The typical clinical manifestations of GCA are new headache, jaw claudication and visual loss. PMR and GCA usually remit within 6 months to 2 years from disease onset. Some patients, however, have a relapsing course and might require long-standing treatment. Diagnosis of PMR and GCA is based on clinical features and elevated levels of inflammatory markers. Temporal artery biopsy remains the gold standard to support the diagnosis of GCA; imaging studies are useful to delineate large-vessel involvement in GCA. Glucocorticoids remain the cornerstone of treatment of both PMR and GCA, but patients with GCA require higher doses. Synthetic immunosuppressive drugs also have a role in disease management, whereas the role of biologic agents is currently unclear.

The introduction of peptide receptor radionuclide therapy, mainly performed with 90Y and 177Lu-labelled somatostatin analogues, has widened the therapeutic horizon of nuclear medicine.

Hodgkin's lymphoma (HL) is a lymphoproliferative malignancy that frequently affects young people. Because patients with HL are often cured, this neoplasm serves as a clinical laboratory for investigating the late effects of cancer therapy. The “hot” issues today are, in advanced stages, how to identify the best strategy to reduce the rate of resistant diseases and, in the early stages, how to minimize late toxicity due to both chemotherapy and radiotherapy (RT). Literature data revealed that PET as a very promising tool in the management of HL. The main applications of FDG-PET in HL are in staging, therapy monitoring, response assessing and follow-up. Recent data show that early PET seems to play a role in predicting the treatment outcome. In RT FDG-PET improves the accuracy in the disease localization and staging with changes in radiation treatment planning in one third of patients with early-stage HL. It also reduces the subjectivity in lymphoma RT field determination, one of the major causes of uncertainty in radiation treatments. The impact of FDGPET will be greater as more conformal RT is planned. In conclusion, the highly curable early stage Hodgkin lymphomas require careful evaluation and balance of the available treatments, in order to achieve a really individualized solution, reducing radiation doses and/or fields dimension and using new advanced techniques.

Accurate delineation of the gross tumour volume (GTV) in radiation therapy process is mandatory, especially when sophisticated techniques for radiotherapy delivery are used. Functional imaging, particularly PET and its fusion with anatomical modalities, such as PET/CT, promises to improve detection and characterization of disease. Quantitative accuracy in PET imaging is affected by several factors, which influence PET data so as to accurately delineate volume for radiotherapy planning purpose. Several strategies in using PET for target volume definition in radiotherapy treatment planning are being explored in the last years. In the present paper we give an overview of different techniques proposed to generate PET-based tumour volumes and the potential of their use in the radiation oncology process.

The rapid increasing prevalence of obesity worldwide represents a serious health hazard. Obesity predisposes to increased risk for diabetes, hypertension, renal failure. Direct mechanisms link visceral adiposity and the atherosclerosis process through the action of adipose-derived proinflammatory cytokines. In particular, hypertension can be considered the most important cardiovascular risk factor linking obesity to the development of cardiovascular disease. Obesity among children and adolescents has also reaching epidemic proportions in the industrialized world. Childhood obesity strongly predisposes to cardiovascular adult mortality. Recent reports documented a tracking of blood pressure from childhood to adulthood and obesity occurring in young age plays a crucial pathogenic role. Indeed, fighting overweight and obesity in the pediatric and adolescent age may prevent the occurrence of adults with hypertension and cardiovascular disease. The main strategies for prevention and treatment of overweight and obesity in childhood, which need to involve community, school and family, are the promotion of lifestyle interventions, including as a correct dietary approach, rich in fruit and vegetables and low-fat dairy products, and physical activity.

This work presents a new search for magnetic monopoles using data taken with the ANTARES neutrino telescope over a period of 10 years (January 2008 to December 2017). Compared to previous ANTARES searches, this analysis uses a run-by-run simulation strategy, with a larger exposure as well as a new simulation of magnetic monopoles taking into account the Kasama, Yang and Goldhaber model for their interaction cross-section with matter. No signal compatible with the passage of relativistic magnetic monopoles is observed, and upper limits on the flux of magnetic monopoles with β=v/c≥0.55, are presented. For ultra-relativistic magnetic monopoles the flux limit is ∼7×10−18 cm−2s−1sr−1.

The endothelium is not merely a barrier but it plays a key role in the maintenance of vascular homeostasis. A dysfunctional endothelium is an early marker of the development of atherosclerotic changes and can also contribute to cardiovascular events. Vascular reactivity tests represent the most widely used methods in the clinical assessment of endothelial function and in the last two decades, several methodologies were developed to study it non invasively in the peripheral macrocirculation (conduit arteries) and microcirculation (resistance arteries and arterioles). This review will centre on the most relevant available non-invasive techniques in the research on endothelial function, their advantages and limitations. Flow mediated dilation (FMD) of the brachial artery by ultrasounds is the most widely used vascular test to assess endothelium- dependent vasodilation. Other approaches include measurement of microcirculatory reactive hyperaemia by forearm venous pletysmography or digital pulse amplitude tonometry, response to 2 agonist by applanation tonometry or digital photoplethysmography and several test by skin laser doppler. It appears that FMD is the most reproducible test when an appropriate and accurate methodology is applied. Recently, post-ischemic vasodilation in the cavernous arteries was also suggested to study endothelial function in patients with erectile dysfunction. Systemic markers proposed as measures of NO biology, inflammatory cytokines, adhesion molecules, or markers of endothelial damage and repair have only a very limited role as a result of biological and assay availability and variability, these factors currently have a limited role in the assessment of individual patients. The optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Therefore, no available test to assess endothelial function has sufficient sensitivity and specificity to be used yet in clinical practice. Only the growing concordant results from different reproducible and reliable non-invasive methods exploring endothelial function with different stimuli will support and strengthen experimental findings, thus providing conclusive answers in this area of research.

Introduction.The administration of immuno-chemotherapy (ICT) followed by rituximab maintenance (RM) is the recommended approach for the front-line therapy of high tumor burden follicular lymphoma (HTB-FL) patients. Among available ICT regimens, RB (Rituximab-bendamustine) and R-CHOP regimen, are preferred options with high, similar efficacy. Regarding RM, its use is strongly supported after R-CHOP by the results of the PRIMA randomized trial; conversely, no prospective data are available to confirm the efficacy of RM in patients initially treated with RB. The FOLL12 trial was conducted to try to demonstrate that a response adapted post induction management of patients with HTB-FL could be as effective as standard RM in terms of Progression Free Survival (PFS). The trial actually showed the better efficacy of standard RM compared to the experimental approach thus providing indirect confirmation of the efficacy of RM after ICT, 10 years after the PRIMA trial. We here analyse the impact of initial ICT in the FOLL12 study that left treatment choice between RB and R-CHOP at physician discretion and on an individual patient basis.

Anthropometric characteristics and dietary habits are widely recognized to influence blood pressure. We evaluated their role in a large series of Mediterranean adult women.

A large body of evidence indicates that patients with essential hypertension, and even more those with complicated hypertension, are characterized by endothelial dysfunction characterized by impaired NO availability secondary to oxidative stress production. A dysfunctioning endothelium is an early marker of the development of atherosclerotic changes and can also contribute to cardiovascular events. Vascular reactivity tests represent the most widely used methods in the clinical assessment of endothelial function. In the last two decades, many studies have evaluated the endothelium in hypertensive patients, using different techniques. Several methodologies were developed to study microcirculation (resistance arteries and arterioles) and macrocirculation (conduit arteries), both in coronary and peripheral vascular districts. This review will centre on the most relevant available techniques in the research on endothelial dysfunction in essential hypertension, their advantages and limitations, focusing on available data on endothelial dysfunction which characterizes patients with complicated hypertension. No available test to assess endothelial function has sufficient sensitivity and specificity to be used in clinical practice. Therefore, the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Only the growing concordant results from different reproducible and reliable methods exploring endothelial function with different stimuli will support and strengthen experimental findings, thus providing conclusive answers in this area of research.