Lifelong bilingualism and mechanisms of neuroprotection in Alzheimer dementia.

Lifelong bilingualism is associated with delayed dementia onset, suggesting a protective effect on the brain. Here, we aim to study the effects of lifelong bilingualism as a dichotomous and continuous phenomenon, on brain metabolism and connectivity in individuals with Alzheimer's dementia. Ninety-eight patients with Alzheimer's dementia (56 monolinguals; 42 bilinguals) from three centers entered the study. All underwent an [18F]-fluorodeoxyglucose positron emission tomography (PET) imaging session. A language background questionnaire measured the level of language use for conversation and reading. Severity of brain hypometabolism and strength of connectivity of the major neurocognitive networks was compared across monolingual and bilingual individuals, and tested against the frequency of second language life-long usage. Age, years of education, and MMSE score were included in all above mentioned analyses as nuisance covariates. Cerebral hypometabolism was more severe in bilingual compared to monolingual patients; severity of hypometabolism positively correlated with the degree of second language use. The metabolic connectivity analyses showed increased connectivity in the executive, language, and anterior default mode networks in bilingual compared to monolingual patients. The change in neuronal connectivity was stronger in subjects with higher second language use. All effects were most pronounced in the left cerebral hemisphere. The neuroprotective effects of lifelong bilingualism act both against neurodegenerative processes and through the modulation of brain networks connectivity. These findings highlight the relevance of lifelong bilingualism in brain reserve and compensation, supporting bilingual education and social interventions aimed at usage, and maintenance of two or more languages, including dialects, especially crucial in the elderly people.

Prevalence of interstitial pneumonia suggestive of COVID-19 at 18F-FDG PET/CT in oncological asymptomatic patients in a high prevalence country during pandemic period: a national multi-centric retrospective study.

PURPOSE: To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) ([18F]FDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus. METHODS: This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January-February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET. RESULTS: Overall, [18F]FDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) (p < 0.001). Instead, no significant difference among pre-COVID and control periods was present. The prevalence of interstitial pneumonia detected at PET/CT was directly associated with geographic virus diffusion, with the higher rate in Northern Italy. Among 284 interstitial pneumonia detected during COVID period, 169 (59%) were FDG-avid (average SUVmax of 4.1). CONCLUSIONS: A significant increase of interstitial pneumonia incidentally detected with [18F]FDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management.

The impact of bilingualism on brain reserve and metabolic connectivity in Alzheimer's dementia.

Cognitive reserve (CR) prevents cognitive decline and delays neurodegeneration. Recent epidemiological evidence suggests that lifelong bilingualism may act as CR delaying the onset of dementia by ∼4.5 y. Much controversy surrounds the issue of bilingualism and its putative neuroprotective effects. We studied brain metabolism, a direct index of synaptic function and density, and neural connectivity to shed light on the effects of bilingualism in vivo in Alzheimer's dementia (AD). Eighty-five patients with probable AD and matched for disease duration (45 German-Italian bilingual speakers and 40 monolingual speakers) were included. Notably, bilingual individuals were on average 5 y older than their monolingual peers. In agreement with our predictions and with models of CR, cerebral hypometabolism was more severe in the group of bilingual individuals with AD. The metabolic connectivity analyses crucially supported the neuroprotective effect of bilingualism by showing an increased connectivity in the executive control and the default mode networks in the bilingual, compared with the monolingual, AD patients. Furthermore, the degree of lifelong bilingualism (i.e., high, moderate, or low use) was significantly correlated to functional modulations in crucial neural networks, suggesting both neural reserve and compensatory mechanisms. These findings indicate that lifelong bilingualism acts as a powerful CR proxy in dementia and exerts neuroprotective effects against neurodegeneration. Delaying the onset of dementia is a top priority of modern societies, and the present in vivo neurobiological evidence should stimulate social programs and interventions to support bilingual or multilingual education and the maintenance of the second language among senior citizens.

Performance of FDG-PET/CT in solitary pulmonary nodule based on pre-test likelihood of malignancy: results from the ITALIAN retrospective multicenter trial.

PURPOSE: The aim of this study was to determine the performance of 18F-FDG-PET/CT in patients with solitary pulmonary nodule (SPN), stratifying the risk according to the likelihood of pulmonary malignancy. METHODS: FDG-PET/CT of 502 patients, stratified for pre-test cancer risk, were retrospectively analyzed. FDG uptake in SPN was assessed by a 4-point scoring system and semiquantitative analysis using the ratio between SUVmax in SPN and SUVmean in mediastinal blood pool (BP) and between SUVmax in SPN and SUVmean in liver (L). Histopathology and/or follow-up data were used as standard of reference. RESULTS: SPN was malignant in 180 (36%) patients, benign in 175 (35%), and indeterminate in 147 (29%). The 355 patients with a definitive SPN nature (malignant or benign) were considered for the analysis. Considering FDG uptake ≥ 2, sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy were 85.6%, 85.7%, 86%, 85.2%, and 85.6% respectively. Sensitivity and PPV were higher (P < 0.05) in intermediate and high-risk patients, while specificity and NPV were higher (P < 0.05) in low-risk patients. On receiver operating characteristic curve analysis, the cut-offs for better discrimination between benign and malignant SPN were 1.56 (sensitivity 81% and specificity 87%) and 1.12 (sensitivity 81% and specificity 86%) for SUVmax/SUVmeanBP and SUVmax/SUVmeanL respectively. In intermediate and high-risk patients, including the SUVmax/SUVmeanBP, the specificity shifted from 85% and 50% to 100%. CONCLUSION: Visual FDG-PET/CT has an acceptable performance in patients with SPN, but accuracy improves when SUVratios are considered, particularly in patients with intermediate and high risk of malignancy.

Risk-related 18F-FDG PET/CT and new diagnostic strategies in patients with solitary pulmonary nodule: the ITALIAN multicenter trial.

PURPOSE: Diagnosis of solitary pulmonary nodule (SPN) is an important public health issue and 18F-FDG PET/CT has proven to be more effective than CT alone. Pre-test risk stratification and clinical presentation of SPN could affect the diagnostic strategy. A relevant issue is whether thoracic segmental (s)-PET/CT could be implemented in patients with SPN. This retrospective multicenter study compared the results of FDG whole-body (wb)-PET/CT to those of s-PET/CT. METHODS: 18F-FDG PET/CT of 502 patients, stratified for pre-test cancer risk, were retrospectively analyzed. The thoracic part of wb-PET/CT, considered s-PET/CT, was compared to wb-PET/CT. Clinical and PET/CT variables were investigated for SPN characterization as well as for identification of patients in whom s-PET/CT could be performed. Histopathology or follow-up data were used as a reference. RESULTS: In the study population, 36% had malignant, 35% benign, and 29% indeterminate SPN. 18F-FDG uptake indicative of thoracic and extra-thoracic lesions was detectable in 13% and 3% of the patients. All patients with extra-thoracic metastases (n = 13) had thoracic lymph node involvement and highest 18F-FDG uptake at level of SPN (negative predictive value 100%). Compared to wb-PET/CT, s-PET/CT could save about 2/3 of 18F-FDG dose, radiation exposure or scan-time, without affecting the clinical impact of PET/CT. CONCLUSION: Pre-test probability of malignancy can guide the diagnostic strategy of 18FDG-PET/CT in patients with SPN. In subjects with low-intermediate pretest probability s-PET/CT imaging might be planned in advance, while in those at high risk and with thoracic lymph node involvement a wb-PET/CT is necessary.

A Prospective Randomized Multicenter Study on the Impact of [18F]F-Choline PET/CT Versus Conventional Imaging for Staging Intermediate- to High-Risk Prostate Cancer.

This study aimed to compare the efficacy of [18F]F-choline PET/CT with conventional imaging for staging and managing intermediate- to high-risk prostate cancer (PCa). The primary objective was to assess the ability of PET/CT with [18F]F-choline to identify lymph node and systemic involvement during initial staging. Secondary objectives included evaluating the impact of [18F]F-choline PET/CT on unnecessary local treatments and assessing the safety of [18F]F-choline agents. Additionally, the study aimed to analyze recurrence-free survival and overall survival 5 y after randomization. Methods: A prospective controlled, open, randomized multicenter phase III trial involving 7 Italian centers was conducted. Eligible patients with intermediate- to high-risk PCa were randomized in a 1:1 ratio. Two groups were formed: one undergoing conventional imaging (abdominopelvic contrast-enhanced CT and bone scanning) and the other receiving conventional imaging plus [18F]F-choline PET/CT. The study was terminated prematurely; however, all the endpoints were thoroughly analyzed and enriched. Results: Between February 2016 and December 2020, 256 patients were randomly assigned. In total, 236 patients (117 in the control arm and 119 in the experimental arm) were considered for the final assessment. In the experimental arm, the sensitivity for lymph node metastases, determined by final pathology and serial prostate-specific antigen evaluations, was higher than in the control arm (77.78% vs. 28.57% and 65.62% vs. 17.65%, respectively). The [18F]F-choline was tolerated well. The use of [18F]F-choline PET/CT resulted in an approximately 8% reduction in unnecessary extended lymphadenectomy compared with contrast-enhanced CT. Additionally, [18F]F-choline PET/CT had a marginal impact on 5-y overall survival, contributing to a 4% increase in survival rates. Conclusion: In the initial staging of PCa, [18F]F-choline PET/CT exhibited diagnostic performance superior to that of conventional imaging for detecting metastases. [18F]F-choline PET/CT reduced the rate of unnecessary extensive lymphadenectomy by up to 8%. These findings support the consideration of discontinuing conventional imaging for staging PCa.

Cutaneous squamous cell carcinoma of the lip successfully treated with rhenium-188 brachytherapy.

Cutaneous squamous cell carcinoma (SCC) is the second most common form of skin cancer. In most cases, non-invasive SCC has a good prognosis and is curable by surgical resection. Nevertheless, a small percentage of patients pose specific management problems due to the technical difficulty of maintaining function and aesthetics because of the size or location of the tumor. An emerging therapeutic approach with high-dose brachytherapy using a nonsealed rhenium-188 resin, commercially known as Rhenium-Skin Cancer Therapy®, has been shown to be highly effective in non-invasive carcinoma, up to a thickness of 2-3 mm.

Applications of Artificial Intelligence and Radiomics in Molecular Hybrid Imaging and Theragnostics for Neuro-Endocrine Neoplasms (NENs).

Nuclear medicine has acquired a crucial role in the management of patients with neuroendocrine neoplasms (NENs) by improving the accuracy of diagnosis and staging as well as their risk stratification and personalized therapies, including radioligand therapies (RLT). Artificial intelligence (AI) and radiomics can enable physicians to further improve the overall efficiency and accuracy of the use of these tools in both diagnostic and therapeutic settings by improving the prediction of the tumor grade, differential diagnosis from other malignancies, assessment of tumor behavior and aggressiveness, and prediction of treatment response. This systematic review aims to describe the state-of-the-art AI and radiomics applications in the molecular imaging of NENs.

Radiomics and artificial intelligence in prostate cancer: new tools for molecular hybrid imaging and theragnostics.

In prostate cancer (PCa), the use of new radiopharmaceuticals has improved the accuracy of diagnosis and staging, refined surveillance strategies, and introduced specific and personalized radioreceptor therapies. Nuclear medicine, therefore, holds great promise for improving the quality of life of PCa patients, through managing and processing a vast amount of molecular imaging data and beyond, using a multi-omics approach and improving patients' risk-stratification for tailored medicine. Artificial intelligence (AI) and radiomics may allow clinicians to improve the overall efficiency and accuracy of using these "big data" in both the diagnostic and theragnostic field: from technical aspects (such as semi-automatization of tumor segmentation, image reconstruction, and interpretation) to clinical outcomes, improving a deeper understanding of the molecular environment of PCa, refining personalized treatment strategies, and increasing the ability to predict the outcome. This systematic review aims to describe the current literature on AI and radiomics applied to molecular imaging of prostate cancer.

Clinical aspects, diagnostic challenges and management of patients with neuroendocrine tumors (NETs).

Neuroendocrine tumor (NET) entities are rare malignancies. Higher awareness and improved diagnostic methods have led to an increasing incidence of these diseases, and most oncologists deal with such patients in their daily practice. The symposium on NETs that was held in Merano (Italy) in October 2009 was organized by the German-speaking European School of Oncology (dESO) and gathered specialists from different disciplines of transalpine countries to bring together experiences and observations regarding these tumors. The goal of the meeting and of this review was to illustrate both well- and poorly differentiated NETs and to encourage interdisciplinary approaches.

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to In Vivo Images.

Lung cancer remains the leading cause of cancer-related death, and it is usually diagnosed in advanced stages (stage III or IV). Recently, the availability of targeted strategies and of immunotherapy with checkpoint inhibitors (ICI) has favorably changed patient prognosis. Treatment outcome is closely related to tumor biology and interaction with the tumor immune microenvironment (TME). While the response in molecular targeted therapies relies on the presence of specific genetic alterations in tumor cells, accurate ICI biomarkers of response are lacking, and clinical outcome likely depends on multiple factors that are both host and tumor-related. This paper is an overview of the ongoing research on predictive factors both from in vitro/ex vivo analysis (ranging from conventional pathology to molecular biology) and in vivo analysis, where molecular imaging is showing an exponential growth and use due to technological advancements and to the new bioinformatics approaches applied to image analyses that allow the recovery of specific features in specific tumor subclones.

FDG PET/CT in the Staging of Lung Cancer.

BACKGROUND: Accurate staging is crucial for the proper management of patients with nonsmall cell lung cancer, especially for choosing the best treatment strategy. Different Imaging methods are used to stage patients with non-small cell lung cancer. In the last two decades, FDG PET/CT is carried out in almost all the main Hospitals around the world in this setting. OBJECTIVE: The aim of this paper is to focus on the value of integrated FDG PET/CT in the TNM staging of the non-small cell lung cancer. METHODS: A non-systematic revision of the literature was performed in order to identify all papers about the role of FDG PET/CT in the evaluation of non-small cell lung cancer and to highlight the value of FDG PET/CT in this setting. RESULTS: Many data are now available about this topic, including also randomized controlled trials. FDG PET/CT is of limited added value in the characterization of T status but it increases the diagnostic accuracy for the assessment of the nodal status. The main advantage of FDG PET/CT over conventional imaging methods is its higher sensitivity in identifying extra-thoracic metastases, especially bone and adrenal lesions. CONCLUSION: PET/CT with FDG should be included in the diagnostic work-up of patients with lung cancer, because it provides useful information for appropriate therapy.

10-Year Clinical Experience With 18F-Choline PET/CT: An Italian Multicenter Retrospective Assessment of 3343 Patients.

PURPOSE: The primary aim of this multicenter retrospective analysis is to examine the role of F-choline PET/CT as a diagnostic tool for staging and restaging prostate cancer (PCa) in a large population in the light of 10 years of clinical experience. A secondary aim of the study is to produce data on the predictors of a positive F-choline PET/CT result in the setting of PCa primaries and biochemical recurrences. MATERIALS AND METHODS: This multicenter retrospective cohort study is based on data collected by 9 Italian nuclear medicine departments. Between October 2008 and September 2019, 3343 men underwent F-choline PET/CT scans before receiving definitive treatments for a primary PCa or biochemical recurrence. Inclusion criteria were (1) histologically proven PCa (on surgical specimens or prostate biopsies from patients not treated surgically) and (2) availability of clinical and pathological data, including serum prostate specific antigen (PSA) level at the time of PET/CT scanning. RESULTS: F-choline PET/CT was performed in 545 cases (16.4%) for cancer staging and in 2798 (83.6%) for restaging purposes, and the result was positive in 540 (99.1%) for the former and 1993 (71.2%) for the latter. A positive PET/CT result was always associated with a high Gleason score (>7) and high PSA levels (P < 0.01). The percentage of patients with a PSA threshold less than 1.0 ng/mL for performing PET/CT was higher in the years 2014 to 2019 (n = 341, 25% of cases) than during the previous period (n = 148, 16%; in 2008-2013). When used for staging purposes, receiver operating characteristic analysis showed that PSA levels of 9.2, 16.4, and 16.6 ng/mL were the optimal cutoffs for distinguishing between positive and negative PET/CT findings for local disease, lymph node involvement, and metastasis, respectively. In the restaging setting, a PSA level of 1.27 ng/mL was the optimal cutoff for distinguishing between a positive and negative PET/CT scan. CONCLUSIONS: F-choline PET/CT can help identify early recurrences, even in the case of low PSA levels (<1 ng/mL). Our data suggest that important improvements have been made in the interpretation of F-choline images and in patient selection in the last 5 years.

11C-acetate PET for early prediction of sunitinib response in metastatic renal cell carcinoma.

Sunitinib is an oral multitargeted tyrosine kinase inhibitor with antiangiogenic properties used for treatment of renal cell carcinoma and gastrointestinal stromal tumors at a dose of 50 mg/day consecutively for 4 weeks followed by 2 weeks off per cycle. At present, no data are available on the early prediction of sunitinib response in renal cell carcinoma. We report a clinical case of a patient with metastatic renal cell carcinoma diagnosed with 11C-acetate PET and conventional CT and treated with sunitinib. Partial and complete remission documented by CT was preceded by early functional tumor inhibition shown by 11C-acetate-PET after only 14 days of therapy. This case report highlights some interesting points related to the potential role of a novel non-FDG PET tracer, 11C-acetate, in the early prediction of the response to targeted therapies in metastatic renal cell carcinoma.

Non-FDG PET/CT in Diagnostic Oncology: a pictorial review.

Positron emission tomography/computed tomography (PET/CT) is currently one of the main imaging modalities for cancer patients worldwide. Fluorodeoxyglucose (FDG) PET/CT has earned its global recognition in the modern management of cancer patients and is rapidly becoming an important imaging modality for patients with cardiac, neurological, and infectious/inflammatory conditions.Despite its proven benefits, FDG has limitations in the assessment of several relevant tumours such as prostate cancer. Therefore, there has been a pressing need for the development and clinical application of different PET radiopharmaceuticals that could image these tumours more precisely. Accordingly, several non-FDG PET radiopharmaceuticals have been introduced into the clinical arena for management of cancer. This trend will undoubtedly continue to spread internationally. The use of PET/CT with different PET radiopharmaceuticals specific to tumour type and biological process being assessed is part of the personalised precision medicine approach.The objective of this publication is to provide a case-based method of understanding normal biodistribution, variants, and pitfalls, including several examples of different imaging appearances for the main oncological indications for each of the new non-FDG PET radiopharmaceuticals. This should facilitate the interpretation and recognition of common variants and pitfalls to ensure that, in clinical practice, the official report is accurate and helpful.Some of these radiopharmaceuticals are already commercially available in many countries (e.g. 68Ga-DOTATATE and DOTATOC), others are in the process of becoming available (e.g. 68Ga-PSMA), and some are still being researched. However, this list is subject to change as some radiopharmaceuticals are increasingly utilised, while others gradually decrease in use.

Reliability and reproducibility of N-[11C]methyl-choline and L-(S-methyl-[11C])methionine solid-phase synthesis: a useful and suitable method in clinical practice.

BACKGROUND AND OBJECTIVE: N-[11C]methyl-choline ([11C]choline) and L-(S-methyl-[11C])methionine ([11C]methionine) are PET radiopharmaceuticals which have gained interest as oncological tracers. The increasing demand of these radiopharmaceuticals needs robust methods of synthesis with high and reproducible yield which provide enough activity for multiple patient administration in a short synthesis time. METHODS: Different synthetic approaches have been described in the literature but exhaustive reports on performance and reliability of different methods have not been described yet. RESULTS AND CONCLUSION: In the present study, we demonstrated the reliability and reproducibility of the solid-phase [11C]methylation method for the synthesis of [11C]choline and [11C]methionine as a suitable tool for the routine clinical use.

Histological verification of positive positron emission tomography findings in the follow-up of patients with mediastinal lymphoma.

BACKGROUND AND OBJECTIVES: Follow-ups of patients with mediastinal lymphoma are not accurate if they rely on computed tomography (CT). Positron emission tomography (PET) has been suggested to be useful in several lymphoma settings, such as initial staging, evaluation of residual masses after therapy, and assessment of response early in the course of treatment. The aim of this retrospective study was to verify the reliability of positive PET scans of the mediastinum in following up patients with mediastinal lymphoma, using histological findings as a comparison. DESIGN AND METHODS: From January 2002 to July 2005, 151 patients with mediastinal lymphoma (57 with Hodgkin's disease [HD] and 94 with aggressive non-Hodgkin's lymphoma [NHL]) were followed-up after the end of front-line treatment. Patients with a positive PET scan of the mediastinum underwent CT scanning and surgical biopsy. RESULTS: In 30 (21 HD and 9 NHL) out of 151 patients (20%) a suspicion of lymphoma relapse was raised based on positive mediastinal PET scanning. Histology confirmed this suspicion in 17 (10 HD and 7 NHL) out of 30 patients (57%), whereas either benign (9 fibrosis, 3 sarcoid-like granulomatosis) or unrelated neoplastic conditions (1 thymoma) were demonstrated in the remaining 13 patients (43%). SUVmax was significantly higher among patients who had signs of relapse (17 true positive cases) than among those who stayed in remission (13 false positive cases), the median values being 5.95 (range, 3.5-26.9) and 2.90 (range, 1.4-3.3), respectively (p=0.01). INTERPRETATION AND CONCLUSIONS: We suggest that a positive PET scan of the mediastinum of a patient being followed-up for a mediastinal lymphoma should not be considered sufficient for diagnostic purposes in view of its lack of discrimination. Histological confirmation can safely be carried out with various biopsy techniques, the choice of which should be made on the basis of the findings of the clinical and imaging studies of the individual case.

Predictive role of positron emission tomography in the outcome of patients with follicular lymphoma.

PURPOSE: The purpose of this study was to evaluate the reliability of positron emission tomography (PET) in patients with follicular lymphoma (FL) after induction treatment. PATIENTS AND METHODS: In all, 45 previously untreated patients with FL were studied with PET and computed tomography (CT) scans after chemotherapy induction treatment (fludarabine-containing regimens and CHOP [cyclophosphamide/doxorubicin/vincristine/prednisone] chemotherapy). Histopathologic analysis was performed when considered necessary. RESULTS: After treatment, 4 of 5 patients (80%) who had CT-negative/PET-positive findings experienced relapse/progression, compared with only 1 of 22 patients (4.5%) in the CT-negative/PET-negative subset. Among the 18 patients with CT-positive findings, all 6 patients (100%) who had PET-positive findings experienced relapse or progression, compared with 1 of 12 patients (8.3%) who had PET-negative findings. The 2-year progression-free survival rates were 20% and 90% in the CT-negative/PET-positive and CT-positive/PET-negative subsets, respectively (P = 0.0031). During the follow-up, 2 patients, who presented a PET positivity with a negative CT scan, underwent a lymph node biopsy, which confirmed the presence of FL infiltration. CONCLUSION: In patients with FL, persisting PET positivity is predictive of early disease progression, because it is still highly likely that patients with PET-negative findings will ultimately progress, but this has not yet been manifested during the period of observation.