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Background/objectives: To evaluate T&N-staging diagnostic performance of [68Ga]Ga-FAPI-46 PET/CT (FAPI) in a suspected/confirmed lung cancer surgical cohort., Methods: Patients were enrolled in a prospective monocentric trial (EudraCT: 2021-006570-23) to perform FAPI, in addition to conventional-staging-flow-chart (including [18F]F-FDG PET/CT-FDG). For the current purpose, only surgical patients were included. PET-semiquantitative parameters were measured for T&N: SUVmax, target-to-background-ratios (using mediastinal blood pool-MBP, liver-L and pulmonary-parenchyma-P). Visual and semiquantitative T&N PET/CT performances were analysed per patient and per region for both tracers, with surgical histopathology as standard-of-truth., Results: 63 FAPI scans were performed in 64 patients enrolled (26 May 2022-30 November 2023). A total of 50/63 patients underwent surgery and were included. Agreement (%) with histopathological-T&N-StagingAJCC8thEdition was slightly in favour of FAPI (T-66% vs. 58%, N-78% vs. 70%), increasing when T&N dichotomised (T-92% vs. 80%, N-78% vs. 72%). The performance of Visual-Criteria for T-per patient (n = 50) resulted higher FAPI than FDG. For N-per patient (n = 46), sensitivity and NPV were slightly lower with FAPI. Among 59 T-regions surgically examined, malignancy was excluded in 6/59 (10%). FAPI showed (vs. FDG): sensitivity 85% (vs. 72%), specificity 67% (vs. 50%), PPV 96% (vs. 93%), NPV 33% (vs. 17%), accuracy 83% (vs. 69%). Among 217 N-stations surgically assessed (overall 746 ln removed), only 15/217 (7%) resulted malignant; FAPI showed (vs. FDG): sensitivity 53% (vs. 60%), PPV 53% (vs. 26%), NPV 97% (vs. 97%), and significantly higher specificity (97% vs. 88%, p = 0.001) and accuracy (94% vs. 86%, p = 0.018). Semiquantitative-PET parameters performed similarly, better for N ( p < 0.001) than for T, slightly in favour (although not significantly) of FAPI over FDG., Conclusions: In a suspected/confirmed lung cancer surgical cohort, PET/CT performances for preoperative T&Nstaging were slightly in favour of FAPI than FDG (except for suboptimal N-sensitivity), significantly better only for N (region-based) specificity and accuracy using visual assessment. The trial's conventional follow-up is still ongoing; future analyses are pending, including non-surgical findings and theoretical impact on patient management.

Background: Image reconstruction is crucial for improving overall image quality and diagnostic accuracy. Q.Clear is a novel reconstruction algorithm that reduces image noise. The aim of the present study is to assess the preferred Q.Clear β-level for digital [ 68 Ga]Ga-DOTANOC PET/CT reconstruction vs. standard reconstruction (STD) for both overall scan and single-lesion visualization. Methods: Inclusion criteria: (1) patients with/suspected neuroendocrine tumors included in a prospective observational monocentric study between September 2019 and January 2022; (2) [ 68 Ga]Ga-DOTANOC digital PET/CT and contrast-enhanced-CT (ceCT) performed at our center at the same time. Images were reconstructed with STD and with Q.Clear β-levels 800, 1000, and 1600. Scans were blindly reviewed by three nuclear-medicine experts: the preferred β-level reconstruction was independently chosen for the visual quality of both the overall scan and the most avid target lesion < 1 cm (t) and >1 cm (T). PET/CT results were compared to ceCT. Semiquantitative analysis was performed (STD vs. β1600) in T and t concordant at both PET/CT and ceCT. Subgroup analysis was also performed in patients presenting discordant t. Results : Overall, 52 patients were included. β1600 reconstruction was considered superior over the others for both overall scan quality and single-lesion detection in all cases. The only significantly different ( p < 0.001) parameters between β1600 and STD were signal-to-noise liver ratio and standard deviation of the liver background. Lesion-dependent parameters were not significantly different in concordant T ( n = 37) and t ( n = 10). Among 26 discordant t, when PET was positive, all findings were confirmed as malignant. Conclusions : β1600 Q.Clear reconstruction for [ 68 Ga]Ga-DOTANOC imaging is feasible and improves image quality for both overall and small-lesion assessment.

Purpose of Review: This paper aims to address the latest findings in neuroendocrine tumor (NET) theranostics, focusing on new evidence and future directions of combined diagnosis with positron emission tomography (PET) and treatment with peptide receptor radionuclide therapy (PRRT)., Recent Findings: Following NETTER-1 trial, PRRT with [177Lu]Lu-DOTATATE was approved by FDA and EMA and is routinely employed in advanced G1 and G2 SST (somatostatin receptor)-expressing NET. Different approaches have been proposed so far to improve the PRRT therapeutic index, encompassing re-treatment protocols, combinations with other therapies and novel indications. Molecular imaging holds a potential added value in characterizing disease biology and heterogeneity using different radiopharmaceuticals (e.g., SST and FDG) and may provide predictive and prognostic parameters. Response assessment criteria are still an unmet need and new theranostic pairs showed preliminary encouraging results. PRRT for NET has become a paradigm of modern theranostics. PRRT holds a favorable toxicity profile, and it is associated with a prolonged time to progression, reduction of symptoms, and improved patients' quality of life. In light of further optimization, different new strategies have been investigated, along with the development of new radiopharmaceuticals., (© 2024. The Author(s).)

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.

Neuroendocrine neoplasms (NEN) are rare and heterogeneous tumors, originating mostly from the gastro-entero-pancreatic (GEP) tract followed by the lungs. Multidisciplinary discussion is mandatory for optimal diagnostic and therapeutic management. Well-differentiated NEN (NET) present a high expression of somatostatin receptors (SSTR) and can be studied with [68Ga]-DOTA-peptides ([68Ga]Ga-DOTANOC, [68Ga]Ga-DOTATOC, [68Ga]Ga-DOTATATE) PET/CT to assess disease extension and the eligibility for peptide receptor radionuclide therapy (PRRT). SSTR-analogues labelled with 90Y or 177Lu have been used since mid-90s for NET therapy. PRRT is now considered an effective and safe treatment option for SSTR-expressing NET: following the approval of 177Lu-DOTATATE by FDA and EMA, PRRT is now part of the therapeutic algorithms of the main scientific societies. New strategies to improve PRRT efficacy and to reduce its toxicity are under evaluation (eg, personalization of treatment schemes, the selection of the most suitable patients, improvement of response assessment criteria, optimization of treatment sequencing, feasibility of PRRT-retreatment, combination of PRRT with other treatments options). Recently, several emerging radiopharmaceuticals showed encouraging results for both imaging and therapy (eg, SSTR-analogues labelled with 18F, SSTR-antagonists for both diagnosis and therapy, alpha-labelling for therapy, radiopharmaceuticals binding to new cellular targets). Aim of this review is to focus on current knowledge and to outline emerging perspectives for NEN's diagnosis and therapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Non-Hodgkin lymphomas represents a heterogeneous group of lymphoproliferative disorders characterized by different clinical courses, varying from indolent to highly aggressive. 18 F-FDG-PET/CT is the current state-of-the-art diagnostic imaging, for the staging, restaging and evaluation of response to treatment in lymphomas with avidity for 18 F-FDG, despite it is not routinely recommended for surveillance. PET-based response criteria (using five-point Deauville Score) are nowadays uniformly applied in FDG-avid lymphomas. In this review, a comprehensive overview of the role of 18 F-FDG-PET in Non-Hodgkin lymphomas is provided, at each relevant point of patient management, particularly focusing on recent advances on diffuse large B-cell lymphoma and follicular lymphoma, with brief updates also on other histotypes (such as marginal zone, mantle cell, primary mediastinal- B cell lymphoma and T cell lymphoma). PET-derived semiquantitative factors useful for patient stratification and prognostication and emerging radiomics research are also presented., (Copyright © 2022. Published by Elsevier Inc.)

Background: This study aimed to analyze the predictive value of Hepatobiliary scintigraphy (HBS) for posthepatectomy liver failure (PHLF) after major liver resection with a comparison to assessment of liver volume in a multicenter cohort., Methods: Patients who underwent liver resection after HBS were included from six centers. Remnant liver volume was calculated from CT images. PHLF was scored and graded according to the grade B/C ISGLS criteria., Results: In 547 patients PHLF incidence was 10% (56/547) and 90-day mortality rate 8% (42/547). Overall predictive value of remnant liver function was 0.66 (0.58-0.74) and similar to that of remnant volume (0.63 (0.72). For biliary tumors, a function cut-off of 2.7%/min/m2 and 30% volume cut-off resulted in a PHLF rate 12% and 13%, respectively. While an 8.5%/min (4.5%/min/m2) function cut-off resulted in 7% PHLF for those with a function above the cutoff while a 40% volume cutoff still resulted in 14% PHLF rate. In the multivariable analyses for PHLF, liver function was predictive but liver volume was not., Conclusion: The current study shows that preoperative liver function assessment using HBS is at least as predictive for PHLF as liver volume assessment, and likely has several advantages, particularly in the high-risk sub-group of biliary tumors., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This is a case of [ 68 Ga]Ga-Prostate-specific membrane antigen (PSMA)-11 PET/CT in a 73-years old patient presenting high Prostate Specific Antigen (PSA) levels despite both multi-parametric magnetic resonance imaging (mpMRI) and 12-core saturation biopsy negative for prostate cancer (Pca). This is a highly interesting case because, despite the advanced metastatic spread at initial presentation as showed by [ 68 Ga]Ga-PSMA-PET/CT, the primary Pca was detected by none of the diagnostic techniques (12 random sample biopsy, mpMRI, PSMA PET/CT). However, [ 68 Ga]Ga-PSMA-PET/CT showed a suspicious axillary lesion suitable for biopsy, which finally resulted as Pca metastasis. This case report is therefore a brilliant example of how [ 68 Ga]Ga-PSMA-PET/CT optimized patient's management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vetrone, Cuzzani, Mei, Zanoni, Bertaccini, Bianchi, Castellucci, Gaudiano, Cappelli, Giunchi and Fanti.)

Background and Aim: The American College of Radiology (ACR) defines "actionable findings" the ones requiring a special communication between radiologists and referring clinicians, suggesting to organize their categorization in a three-degree scale on the basis of the risk for the patient to develop complications. These cases may fall in a grey-zone communication between different care figures with the risk of being underestimated or even not being considered at all. In this paper, our aim is to adapt the ACR categorization to the most frequent actionable findings encountered when reporting PET/CT images in a Nuclear Medicine Department, describing the most frequent and relevant imaging features and presenting the modalities of communication and the related clinical interventions that can be modulated by the prognostic severity of the clinical cases., Materials and Methods: We performed a descriptive, observational and critical analysis of the most relevant literature on the topic of "actionable findings", in particular, starting from the reports of the ACR Actionable Reporting Work Group, we categorised and described, in a narrative review, the most relevant "actionable findings" encountered in the Nuclear Medicine PET/CT daily practice., Results: To the best of our knowledge, to date there are no clear indications on this selective PET/CT topic, considering that the current recommendations target mainly radiologists and assume a certain level of radiological expertise. We resumed and classified the main imaging conditions under the term of "actionable findings" according to the corresponding anatomical districts, and we described their most relevant imaging features (independently of PET avidity or not). Furthermore, a different communication timing and strategy was suggested on the basis of the findings' urgency., Conclusion: A systematic categorization of the actionable imaging findings according to their prognostic severity may help the reporting physician to choose how and when to communicate with the referring clinician or to identify cases requiring a prompt clinical evaluation. Effective communication is a critical component of diagnostic imaging: timely receipt of the information is more important than the method of delivery., Competing Interests: Conflict of interestAll the authors declare no conflict of interest regarding this topic., (© The Author(s), under exclusive licence to Italian Association of Nuclear Medicine and Molecular Imaging 2023, corrected publication 2023Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Abstract: Polymyalgia rheumatica is the most common inflammatory rheumatic disease in elderly people, usually develops in patients older than 50 years, more frequently in females. An emerging imaging tool in the diagnostic workup of this condition is whole-body PET/CT, which allows an overall assessment of the articular and extra-articular structures involved., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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&#95;LSNR (LSNR&#95;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&#95;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*m 2 /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).

Aim/introduction: Digital PET/CT allows Q.Clear image reconstruction with different Beta (β) levels. However, no definitive standard β 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 β 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 β levels (800, 1000, 1600). Scans were independently reviewed by three expert readers, unaware of clinical data, who independently chose the preferred β 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 β1600 was preferred in most cases (in 96% of obese patients and in 53.3% of pre-obese cases). OSEM was considered visually equal to β1600 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 β1600, conversely to SUVmean-L (not significant). These results were also confirmed when calculated separately for the pre-obesity and obesity sub-groups β800 and β1000 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, β1600 is preferable over β800 and β1000. 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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors that require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with 68 Ga for diagnosis and with 90 Y or 177 Lu for therapy) plays a crucial role in the management of NENs to assess disease extension and as a criteria for peptide receptor radionuclide therapy (PRRT) eligibility based on somatostatin receptor (SSTR) expression. On the diagnostic side, [ 68 Ga]Ga-DOTA peptides PET/CT (SSTR PET/CT) is the gold standard for imaging well-differentiated SSTR-expressing neuroendocrine tumors (NETs). [ 18 F]FDG PET/CT is useful in higher grade NENs (NET G2 with Ki-67 > 10% and NET G3; NEC) for more accurate disease characterization and prognostication. Promising emerging radiopharmaceuticals include somatostatin analogues labelled with 18 F (to overcome the limits imposed by 68 Ga), and SSTR antagonists (for both diagnosis and therapy). On the therapeutic side, the evidence gathered over the past two decades indicates that PRRT is to be considered as an effective and safe treatment option for SSTR-expressing NETs, and is currently included in the therapeutic algorithms of the main scientific societies. The positioning of PRRT in the treatment sequence, as well as treatment personalization (e.g., tailored dosimetry, re-treatment, selection criteria, and combination with other alternative treatment options), is warranted in order to improve its efficacy while reducing toxicity. Although very preliminary (being mostly hampered by lack of methodological standardization, especially regarding feature selection/extraction) and often including small patient cohorts, radiomic studies in NETs are also presented. To date, the implementation of radiomics in clinical practice is still unclear. The purpose of this review is to offer an overview of radiolabeled SSTR analogues for theranostic use in NENs.

Purpose: The conventional imaging flowchart for prostate cancer (PCa) staging may fail in correctly detecting lymph node metastases (LNM). Pelvic lymph node dissection (PLND) represents the only reliable method, although invasive. A new amino acid PET compound, [ 18 F]-fluciclovine, was recently authorized in suspected PCa recurrence but not yet included in the standard staging work-up of primary PCa. A prospective monocentric study was designed to evaluate [ 18 F]-fluciclovine PET/CT diagnostic performance for preoperative LN staging in primary high-risk PCa., Methods: Consecutive patients (pts) with biopsy-proven PCa, standard staging (including [ 11 C]choline PET/CT), eligible for PLND, were enrolled to undergo an investigational [ 18 F]-fluciclovine PET/CT. Nodal uptake higher than surrounding background was reported by at least two readers (blinded to [ 11 C]choline) using a visual 5-point scale (1-2 probably negative; 4-5 probably positive; 3 equivocal); SUVmax, target-to-background (aorta-A; bone marrow-BM) ratios (TBRs), were also calculated. PET results were validated with PLND. [ 18 F]-fluciclovine PET/CT performance using visual score and semi-quantitative indexes was analyzed both per patient and per LN anatomical region, compared to conventional [ 11 C]choline and clinical predictive factors (to note that diagnostic performance of [ 18 F]-fluciclovine was explored for LNM but not examined for intrapelvic or extrapelvic M1 lesions)., Results: Overall, 94 pts underwent [ 18 F]-fluciclovine PET/CT; 72/94 (77%) high-risk pts were included in the final analyses (22 pts excluded: 8 limited PLND; 3 intermediate-risk; 2 treated with radiotherapy; 4 found to be M1; 5 neoadjuvant hormonal therapy). Median LNM risk by Briganti nomogram was 19%. LNM confirmed on histology was 25% (18/72 pts). Overall, 1671 LN were retrieved; 45/1671 (3%) LNM detected. Per pt, median no. of removed LN was 22 (mean 23 ± 10; range 8-51), of LNM was 2 (mean 3 ± 2; range 1-10). Median LNM size was 5 mm (mean 5 ± 2.5; range 2-10). On patient-based analyses (n = 72), diagnostic performance for LNM resulted significant with [ 18 F]-fluciclovine (AUC 0.66, p 0.04; 50% sensitivity, 81% specificity, 47% PPV, 83% NPV, 74% accuracy), but not with [ 11 C]choline (AUC 0.60, p 0.2; 50%, 70%, 36%, 81%, and 65% respectively). Briganti nomogram (OR = 1.03, p = 0.04) and [ 18 F]-fluciclovine visual score (≥ 4) (OR = 4.27, p = 0.02) resulted independent predictors of LNM at multivariable analyses. On region-based semi-quantitative analyses (n = 576), PET/CT performed better using TBR parameters (TBR-A similar to TBR-BM; TBR-A fluciclovine AUC 0.61, p 0.35, vs choline AUC 0.57 p 0.54; TBR-BM fluciclovine AUC 0.61, p 0.36, vs choline AUC 0.58, p 0.52) rather than using absolute LN SUVmax (fluciclovine AUC 0.51, p 0.91, vs choline AUC 0.51, p 0.94). However, in all cases, diagnostic performance was not statistically significant for LNM detection, although slightly in favor of the experimental tracer [ 18 F]-fluciclovine for each parameter. On the contrary, visual interpretation significantly outperformed PET semi-quantitative parameters (choline and fluciclovine: AUC 0.65 and 0.64 respectively; p 0.03) and represents an independent predictive factor of LNM with both tracers, in particular [ 18 F]-fluciclovine (OR = 8.70, p 0.002, vs OR = 3.98, p = 0.03)., Conclusion: In high-risk primary PCa, [ 18 F]-fluciclovine demonstrates some advantages compared with [ 11 C]choline but sensitivity for metastatic LN detection is still inadequate compared to PLND. Visual (combined morphological and functional), compared to semi-quantitative assessment, is promising but relies mainly on readers' experience rather than on unquestionable LN avidity., Trial Registration: EudraCT number: 2014-003,165-15., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

2-deoxy-2-[ 18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET) gained an impressive role in the diagnostic management of many oncological diseases, even though its use in imaging prostate cancer (PC) is limited to selected cases, mostly advanced stage of PC and selection for prostate specific antigen membrane (PSMA) radioligand therapy (RLT). In the past years, several PET tracers have been developed for both staging and restaging PC. The three most employed PET molecules in daily practice are [ 11 C] or [ 18 F]F-Choline, [ 18 F]F-Fluciclovine (Anti-1- amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid, also known as (Anti-[ 18 F]FACBC), [ 68 Ga]Ga-PSMA and recently FDA approved the first Fluorinated PSMA-based named [ 18 F]F-DCFPyl. Each one has its own physiological and peculiarity which are worth exploring. Moreover, an increasing number of case reports and studies have reported tracers' variants, pitfalls, or even non-prostatic diseases (benign and malignant) incidentally detected. In prostate oncology, PET can be performed with several indications in different stages of disease, as highlighted in the EAU Guidelines on PC. A correct scan interpretation depends on the knowledge of both the physiological distribution of the tracers and the uptake of possible variants and pitfalls. The aim of this critical review is to provide a comprehensive knowledge of physiological distribution of these three tracers, as well as an updated overview of variants and pitfalls., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright © 2021. Published by Elsevier B.V.)

The primary aim of the study was to evaluate the role of [ 18 F]Fluciclovine PET/CT in the characterization of intra-prostatic lesions in high-risk primary PCa patients eligible for radical prostatectomy, in comparison with conventional [ 11 C]Choline PET/CT and validated by prostatectomy pathologic examination. Secondary aims were to determine the performance of PET semi-quantitative parameters (SUVmax; target-to-background ratios [TBRs], using abdominal aorta, bone marrow and liver as backgrounds) for malignant lesion detection (and best cut-off values) and to search predictive factors of malignancy. A six sextants prostate template was created and used by PET readers and pathologists for data comparison and validation. PET visual and semi-quantitative analyses were performed: for instance, patient-based, blinded to histopathology; subsequently lesion-based, un-blinded, according to the pathology reference template. Among 19 patients included (mean age 63 years, 89% high and 11% very-high-risk, mean PSA 9.15 ng/mL), 45 malignant and 31 benign lesions were found and 19 healthy areas were selected ( n = 95). For both tracers, the location of the "blinded" prostate SUVmax matched with the lobe of the lesion with the highest pGS in 17/19 cases (89%). There was direct correlation between [ 18 F]Fluciclovine uptake values and pISUP. Overall, lesion-based ( n = 95), the performance of PET semiquantitative parameters, with either [ 18 F]Fluciclovine or [ 11 C]Choline, in detecting either malignant/ISUP2-5/ISUP4-5 PCa lesions, was moderate and similar (AUCs ≥ 0.70) but still inadequate (AUCs ≤ 0.81) as a standalone staging procedure. A [ 18 F]Fluciclovine TBR-L3 ≥ 1.5 would depict a clinical significant lesion with a sensitivity and specificity of 85% and 68% respectively; whereas a SUVmax cut-off value of 4 would be able to identify a ISUP 4-5 lesion in all cases (sensitivity 100%), although with low specificity (52%). TBRs (especially with threshold significantly higher than aorta and slightly higher than bone marrow), may be complementary to implement malignancy targeting.

Hepatobiliary scintigraphy (HBS) has been demonstrated to predict post-hepatectomy liver failure (PHLF). However, existing cutoff values for future liver remnant function (FLR-F) were previously set according to the "50-50 criteria" PHLF definition. Methods of calculation and fields of application in liver surgery have changed in the meantime. The aim of this study was to demonstrate the role of HBS combined with single photon emission computed tomography (SPECT/CT) in predicting severity of PHLF, according to the International Study Group of Liver Surgery (ISGLS). All patients submitted to major hepatectomy with preoperative HBS-SPECT/CT between November 2016 and December 2019, were analyzed. Patients were resected according to hepatic volumetry. Receiver operating characteristic (ROC) curve analysis was performed to identify cutoffs of FLR function for predicting PHLF according to ISGLS definition and grading. Of the 38 patients enrolled, 26 were submitted to one-stage hepatectomy (living liver donors = 4) and 12 to two-stage procedures (portal vein embolization = 4, ALPPS = 8). Overall, 18 patients developed PHLF according to ISGLS criteria: 12 of grade A (no change in the patient's clinical management) and 6 of grade B (change in clinical management). ROC analysis established increasingly higher cutoffs of FLR-F for predicting PHLF according to the "50-50 criteria", ISGLS grade B and ISGLS grade A/B, respectively. HBS with SPECT/CT may help to assess severity of PHLF following major hepatectomy. Prospective multicenter trials are needed to confirm the effective role of HBS-SPECT/CT in liver surgery.

Objectives: Visceral leishmaniasis (VL) is the most severe manifestation of the infection caused by the protozoan Leishmania, recently on increase in Italy and Spain. The aim of the study was to describe FDG uptake patterns in VL patients (pts) who underwent 18F-FDG PET/CT., Methods: A retrospective monocentric study of pts who underwent FDG PET/CT between 2008 and 2017 and later diagnosed with VL was performed. Semi-quantitative parameters were calculated in FDG-positive lesions: SUVmax, SUVmax spleen/SUVmax liver ratio (SLR), SUVmax focal/diffuse spleen ratio (FDR)., Results: Overall, 23 pts were included. PET/CT was negative in 2 immunocompromised pts, positive in 21/23 (91%) [6 spleen only, 2 spleen + nodes, 7 spleen + bone marrow (BM), 4 spleen + BM + nodes, 1 spleen + BM + lung, 1 BM only + nodes, 2 nodes only]. Splenic involvement was demonstrated in 20/23 (87%) pts. Two different splenic patterns were observed: diffuse (13/20 pts, mean spleen SUVmax = 7.3 ± 4.2 [4.0-14.1], mean SLR = 2.2 ± 1.6 [1.3-6.7]) and focal over diffuse (7/20 pts, mean SUVmax = 12.6 ± 4.5 [9.5-20.5], mean SLR = 2.8 ± 0.8 [2.1-4.4], mean FDR = 2.1 ± 0.8 [1.2-3.6]). Extra-splenic FDG-avid findings were detected in 15/21 pts (65%): bone marrow in 13/15 (mean SUVmax = 4.0 ± 1.3 [2.8-6.0]), nodes in 67/15 and lung in 1/15., Conclusions: PET/CT demonstrated splenic FDG uptake in all immunocompetent VL pts; two splenic patterns (diffuse/focal over diffuse) were observed and indistinguishable from splenic involvement by other disorders. The most frequent extra-splenic FDG-positive sites were BM and lymph nodes. Considering the potential disease aggressiveness and recent outbreaks in north-eastern Italy, VL should be considered in the differential diagnosis of FDG-positive splenic findings in pts from endemic areas or reporting travels to endemic countries.

Prostate cancer is the most common cancer and the second leading cause of cancer death in men in the United States. Despite high prevalence, diagnosis and surveillance is limited due to indolent biology. Functional imaging techniques improved the ability to detect disease. Amino acids are building blocks of proteins and intracellular transport is upregulated in prostate cancer. Normal biodistribution patterns of fluciclovine include uptake in the liver and pancreas with minimal to no urine excretion, a distinct advantage for prostate cancer imaging. This review provides a detailed overview of the use of F-18 fluciclovine PET in prostate cancer imaging., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A significant number of patients radically treated for prostate cancer (PCa) will develop prostate-specific antigen recurrence (27-53%). Localizing the anatomical site of relapse is critical, in order to achieve the optimal treatment management. To date the diagnostic accuracy of standard imaging is low. Several desirable features have been identified for the amino-acid-based PET agent, fluciclovine ( 18 F) including: long 18 F half-life which allows more practical use in centers without a cyclotron onsite; acting as a substrate for amino acid transporters upregulated in PCa or associated with malignant phenotype; lacking of incorporation into protein; and limited urinary excretion. Fluciclovine ( 18 F) is currently approved both in USA and Europe with specific indication in adult men with suspected recurrent PCa based on elevated prostate-specific antigen following prior treatment.

A patient multiple endocrine neoplasia type 1 presenting with radiological suspicion of pancreatic neuroendocrine tumor relapse after surgical and somatostatin analog treatment underwent restaging Ga-DOTANOC PET/CT. Standard and delayed images detected an area of focal intense uptake moving from the left para-aortic to the paracaval region. The lesion was identified at previous imaging in different abdominal locations (eg, adjacent to the duodenal wall at presurgical PET and in the aortocaval region at restaging contrast-enhanced CT). Dual time-point Ga-DOTANOC PET/CT was crucial to accurately diagnose the wandering mesenteric lymph node, a potential interpretation pitfall especially when found far from the initial position.

Prostate cancer is the most common cancer and the second leading cause of cancer death in men in the United States. Despite high disease prevalence, diagnosis and surveillance of the disease with conventional imaging are limited typically because of indolent biology. Functional imaging with advanced molecular techniques improves the ability to detect disease. Amino acids are building blocks of proteins, and intracellular transport of amino acids is upregulated in prostate cancer. This review provides a detailed overview of the use of F-18 fluciclovine PET in prostate cancer imaging., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To compare the accuracy of (18)F-FACBC and (11)C-choline PET/CT in patients radically treated for prostate cancer presenting with biochemical relapse., Methods: This prospective study enrolled 100 consecutive patients radically treated for prostate cancer and presenting with rising PSA. Of these 100 patients, 89 were included in the analysis. All had biochemical relapse after radical prostatectomy (at least 3 months previously), had (11)C-choline and (18)F-FACBC PET/CT performed within 1 week and were off hormonal therapy at the time of the scans. The two tracers were compared directly in terms of overall positivity/negativity on both a per-patient basis and a per-site basis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for both the tracers; follow-up at 1 year (including correlative imaging, PSA trend and pathology when available) was considered as the standard of reference., Results: In 51 patients the results were negative and in 25 patients positive with both the tracers, in eight patients the results were positive with (18)F-FACBC but negative with (11)C-choline, and in five patients the results were positive with (11)C-choline but negative with (18)F-FACBC. Overall in 49 patients the results were false-negative (FN), in two true-negative, in 24 true-positive (TP) and in none false-positive (FP) with both tracers. In terms of discordances between the tracers: (1) in one patient, the result was FN with (11)C-choline but FP with (18)F-FACBC (lymph node), (2) in seven, FN with (11)C-choline but TP with (18)F-FACBC (lymph node in five, bone in one, local relapse in one), (3) in one, FP with (11)C-choline (lymph node) but TP with (18)F-FACBC (local relapse), (4) in two, FP with (11)C-choline (lymph nodes in one, local relapse in one) but FN with (18)F-FACBC, and (5) in three, TP with (11)C-choline (lymph nodes in two, bone in one) but FN with (18)F-FACBC. With (11)C-choline and (18)F-FACBC, sensitivities were 32 % and 37 %, specificities 40 % and 67 %, accuracies 32 % and 38 %, PPVs 90 % and 97 %, and NPVs 3 % and 4 %, respectively. Categorizing patients by PSA level (<1 ng/ml 28 patients, 1 - <2 ng/ml 28 patients, 2 - <3 ng/ml 11 patients, ≥3 ng/ml 22 patients), the number (percent) of patients with TP findings were generally higher with (18)F-FACBC than with (11)C-choline: six patients (21 %) and four patients (14 %), eight patients (29 %) and eight patients (29 %), five patients (45 %) and four patients (36 %), and 13 patients (59 %) and 11 patients (50 %), respectively., Conclusion: (18)F-FACBC can be considered an alternative tracer superior to (11)C-choline in the setting of patients with biochemical relapse after radical prostatectomy.

Epstein-Barr virus-related post-transplant lymphoproliferative disorder (EBV-PTLD) is an uncommon, but frequently fatal, complication after allogeneic hematopoietic stem cell transplant. Prospective post-transplant virological and immunological monitoring allowed to successfully manage a patient who developed both polymorphic and monomorphic, "diffuse large B-cell lymphoma like", as an EBV-PTLD, 65days after allogeneic bone marrow transplant. Early detection of significant increase in EBV DNA level in patient's peripheral blood (peak of viral load equal to 119,039copies/mL whole blood, +56day after transplant) led to administration of pre-emptive anti-CD20 monoclonal antibody (rituximab) and close clinical monitoring. After one week, physical exam revealed laterocervical adenopathy. Histopathologic features, immunohistochemical characterization and in situ hybridization study allowed to establish a diagnosis of EBV-related PTLD. Immunological monitoring showed no EBV-specific T-cell responses during EBV replication, thus potentially explaining the occurrence of high EBV load with subsequent PTLD development. A total of four doses of anti-CD20 monoclonal antibody were administered and at the end of the treatment, EBV infection was cleared and imaging technique showed complete disease remission. In conclusion, the early use of anti-CD20 monoclonal antibody proved to be a safe and effective treatment strategy for EBV-PTLD. Moreover, combined virological-immunological monitoring of EBV infection may more accurately assess patients at higher risk for EBV-PTLD., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The effect of allergen avoidance on airway inflammation is similar to that observed with treatment with inhaled steroids, whereas inhaled steroids have no effect on oxidative stress-induced inflammation., Objective: The aim of this study was to retrospectively evaluate the potential effect of an antioxidant dietary supplement on exhaled nitric oxide over a month in pediatric patients on stable antiasthma treatment., Methods: Forty-seven children with moderate-to-severe asthma were retrospectively evaluated. All the patients were sensitive to Dermatophagoides pteronyssinus and Dermatophagoides farinae, and they were receiving the minimum inhaled corticosteroid dosage required to maintain adequate control. Within a few weeks of admission at Misurina Hospital in the Alps, the regular treatment was gradually reduced, then some children who were receiving a daily dose of inhaled corticosteroids, ≤200 mcg of fluticasone propionate, were prescribed a nutraceutical dietary supplement for at least 4 weeks. Lung function and fractional exhaled nitric oxide (FeNO) measurements were recorded at the beginning and after 1 month of the dietary supplementation., Results: Baseline lung function and FeNO values did not differ between the two groups of patients. After 4 weeks of nutraceutical supplementation, FeNO values decreased, from 19.00 ppb (interquartile range, 14-31 ppb) to 11.00 ppb (interquartile range, 6-23 ppb) (p = 0.03). No significant reduction was observed in the group that did not receive the supplementation, and no significant difference between groups was observed, both at baseline and after 4 weeks of nutraceutical supplementation., Conclusion: Supplementation with a nutraceutical of antioxidants and anti-inflammatory compounds, such as curcumin, resveratrol, soy phospholipids, zinc, selenium, and vitamin D, may be associated with reduced airway inflammation, as documented by a fall in FeNO.

Aim: The aim of the study was to evaluate the visceral localization of the three most commonly used choline-based radiotracers (C-choline, F-methylcholine, and F-ethylcholine) with the aim of analyzing uptake in metabolically and anatomically disease-free patients., Materials and Methods: A total of 1250 standardized uptake values (SUVmax, SUVmean) were analyzed in 45 anatomical regions in 45 patients (15 patients with C-choline, 15 with F-methylcholine, and 15 with F-ethylcholine). These patients were selected from a cohort of 3721 choline PET/computed tomography studies performed at three teaching hospitals over a period of 10 years. They had no evidence of metabolically active primary disease, metastatic disease, or altered morphology on the computed tomography component of the study or any evidence of disease elsewhere on other imaging modalities. The sites of primary disease (prostate and seminal vesicles) were excluded from evaluation., Results: No adverse effect was documented when using the three tracers. Visceral localization was the same for all three tracers. Viscera with a statistical difference in intensity of uptake included the choroid plexus (P=0.0001), occipital lobe (P=0.014), parietal lobe (P=0.008), cerebellum (P=0.003), parotid gland (P=0.005), submandibular gland (P=0.001), tonsils (P=0.001), thyroid (P=0.0001), lungs (P=0.001), aorta (P=0.001), pulmonary artery (P=0.0001), liver segments I (P=0.005), III (P=0.005), IVB (P=0.03), and V (P=0.01), spleen [hilum (P=0.0009), body (P=0.0001)], pancreas [head (P=0.0001), body (P=0.01), tail (P=0.002)], esophagus (P=0.001), stomach (P=0.0001), duodenum (P=0.0002), large intestine (P=0.008), and rectum (P=0.0001). Elsewhere, no statistical difference was observed. Excreted activity was noted in the kidneys and bladder., Conclusion: This study demonstrates that the visceral localization of C-choline, F-methylcholine, and F-ethylcholine in disease-free patients is similar. Depending on the tracer uptake pattern, the viscera can be divided into two distinct categories: those with a statistically significant difference in uptake and those with no difference in uptake. The study outlines the range of SUVs for various organs for the three tracers and identifies some of the potential pitfalls in the evaluation of 'nonavid' but clinically significant presentation of different disease entities.

Purpose: In recent years, a new PET compound (anti-3-(18)F-FACBC or (18)F-fluciclovine) was tested for the detection of prostate cancer relapse. Despite very promising results, only preliminary data were available with regard to the comparison to (11)C-choline. The aim of this study was to compare the detection rate of (18)F-FACBC and (11)C-choline in patients presenting a biochemical relapse., Patients and Methods: Fifty patients radically treated for prostate cancer and presenting with rising prostate-specific antigen (PSA) levels were consecutively and prospectively enrolled. All the patients were out of hormonal therapy and underwent both (11)C-choline PET/CT and (18)F-fluciclovine PET/CT within 1 week. The results were compared in terms of detection rate on a patient and lesion basis. Furthermore, a more detailed analysis regarding local, lymph node, and bone relapse was performed., Results: On a patient-based analysis, (18)F-fluciclovine detection turned out to be significantly superior to (11)C-choline (P < 0.000001). This result was also true on lesion, lymph node, bone lesion, and local relapse analysis (P < 0.0001 in all the cases). There was no significant difference in terms of target to background of positive lesions between (11)C-choline and (18)F-fluciclovine. When the patients were divided into groups with different PSA levels, (18)F-fluciclovine had a superior detection rate for low, intermediate, and high PSA levels., Conclusions: In our experimental conditions, (18)F-fluciclovine provided a statistically significant better performance in terms of lesion detection rate as compared with (11)C-choline. However, more studies are required to evaluate the clinical significance of these results in terms of sensitivity, specificity, and accuracy.

Purpose: The purpose of this study was to evaluate the performance and possible prognostic value of early (18)F-FDG PET/CT (FDG PET/CT) assessment after radiotherapy (RT) in patients with solitary bone plasmacytoma (SBP)., Methods: Twenty-one patients affected by SBP who underwent FDG PET/CT scan for early restaging (≤6 months) postradiotherapy assessment were selected from the PET databases of University College London Hospital of London and San Raffaele Hospital of Milan. Patients with no abnormal uptake were classified as having no pathologic uptake (NPU). A SUV(max) cutoff value of 4 was chosen to discriminate minimal residual uptake (MRU; SUV(max) ≤ 4) from pathologic uptake (PU, SUV(max) >4). Progression-free survival (PFS) rate was estimated using Kaplan-Meier curves and Cox regression analysis., Results: In 10 of 21 patients restaged by FDG PET/CT, further previous baseline scan was available also at staging, and results showed positive findings at the level of all biopsy-proven disease areas.Considering MRU as PU, FDG PET/CT showed a sensitivity and specificity of 86% and 29%, respectively. Using SUV(max) >4 as the cutoff, sensitivity and specificity were 86% and 93%, respectively. Kaplan-Meier curves revealed a significant difference in PFS probability between patients classified as positive on FDG PET/CT using a cutoff of SUV(max) >4 (PU) and those classified as negative (NPU + MRU) (log-rank, Mantel-Cox, P = 0.009; χ(2) = 6.85). Cox regression analysis of PFS using SUV(max) >4 as cutoff revealed an interesting relation in prediction of progression (HR, 9.458)., Conclusion: (18)F-FDG PET/CT for early restaging after RT in patients with SBP should be considered carefully in view of the lack of specificity of a low SUV(max) value. The good correlation between a high SUV(max) value and follow-up suggests a possible prognostic role for FDG PET/CT in disease progression at early restaging after RT.

The diffusion of PET/computed tomography has opened up a new role for nuclear imaging in urological oncology. Prostate cancer is evaluated with choline ((11)C or (18)F) PET due to a lack of sensitivity of (18)F-fluorodeoxyglucose (FDG). However, many new tracers, such as (18)F-fluorocyclobutane-1-carboxylic acid and (68)Ga-prostate-specific membrane antigen, are under investigation, offering promising results in the particular setting of radically treated patients with biochemical relapse. The performance of (18)F-FDG depends on the histological type; indeed, renal cell cancer may present variable metabolic uptake. In this field, mainly antibodies labeled with positron emitters are under clinical evaluation. Finally, (18)F-FDG PET/computed tomography has been proven to show good accuracy in detecting metastatic testicular and bladder cancers, despite not having valid results in detecting local disease. The urological cancer diagnostic process is currently under continuous development.

Introduction: The aim of our study was to compare the detection rate of anti-3-18F-FACBC PET/CT in comparison with 11C-choline PET/CT in the evaluation of disease recurrence of PCa after radical prostatectomy., Patients and Methods: Twenty-eight consecutive patients with biochemical relapse after radical prostatectomy were submitted to anti-3-18F-FACBC PET/CT and 11C-choline PET/CT to evaluate the site of disease recurrence. Androgen deprivation therapy was avoided in all cases. The primary end point was the overall detection rate of the 2 radiotracers. A patient-based analysis and a lesion-based analysis was performed. The target to background ratio (TBR) of each lesion was reported., Results: At the time of PET scan, mean age was 67 years and mean prostate specific antigen (PSA) relapse was 2.9 ng/mL (range: 0.2-14.6). In patient-based analyses, 11C-choline PET/CT was positive in 5 patients and negative in 23 (detection rate = 17.8%) and anti-3-18F-FACBC PET/CT was positive in 10 patients and negative in 18 (detection rate = 35.7%). All lesions that were positive using 11C-choline were positive using anti-3-18F-FACBC PET/CT but with the latter radiotracer, 11 (61.1%) additional tumors were identified including 5 (17.8%) additional patients. The TBR of anti-3-18F-FACBC was greater than 11C-choline in 15 of 18 lesions, confirming a better image quality and contrast., Conclusion: This preliminary study demonstrated that the detection rate of anti-3-18F-FACBC PET/CT is greater in comparison with 11C-choline, with approximately 20% of additional patients and approximately 60% additional lesions detected. Further studies, however, are required to assess the exact added value of this new tracer., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Breast milk and colostrum are the first feeding sources for a child, providing nutrients, growth factors and immunological components, which are crucial for the newborn's correct development and health. Length of exclusive breastfeeding and time of solid foods introduction is a key factor that may influence allergy development. There is an emerging evidence of a relationship between breastfeeding, milk composition and lower risk of chronic diseases, such as diabetes, obesity, hypertension and allergies. This review examines current evidence regarding humoral and cellular characteristics of breast-milk, and potential role of environment, maternal diet and breastfeeding on the allergy development in children.

Alterations of the cardiac autonomic nervous system play an important role in the pathway of many heart diseases. Nuclear imaging tools have been demonstrated to be useful for global and regional assessment of myocardial innervation. We used (11)C-meta-hydroxy-ephedrine ((11)C-mHED), a catecholamine analogue, as a radiotracer usable with a PET/CT scanner to study the cardiac sympathetic system. After a fast and automatic synthesis of mHED and its labeling with (11)C, we acquired cardiac images by using a PET/ CT scanner. In this paper we present our preliminary results showing the radiotracer bio-distribution in humans 10 minutes post injection. The present study assesses the feasibility of PET/CT with the radiolabeled catecholamine analogue ((11)C-mHED) in order to determine sympathetic innervation in the human heart.

Gallium-68 DOTANOC is a high affinity somatostatin receptor ligand, first introduced in 2005 for imaging neuroendocrine tumors. Due to its technically simple production, broad availability, favourable biodistribution and advantageous dosimetry, although not approved yet in all European countries, gallium-68 DOTANOC has rapidly gained acceptance in the diagnostic and therapeutic work-flow of different types of neuroendocrine tumors. Principal indications in clinical practice in countries where it is officially approved include diagnosis and staging, restaging after treatment, identification of sites of unknown primary and selection of patients with neuroendocrine tumors eligible for therapy with somatostatin analogues.

Purpose: The use of early (interim) PET restaging during first-line therapy of Hodgkin's lymphoma (HL) in clinical practice has considerably increased because of its ability to provide early recognition of treatment failure allowing patients to be transferred to more intensive treatment regimens., Methods: Between June 1997 and June 2009, 304 patients with newly diagnosed HL (147 early stage and 157 advanced stage) were treated with the ABVD regimen at two Italian institutions. Patients underwent PET staging and restaging at baseline, after two cycles of therapy and at the end of the treatment., Results: Of the 304 patients, 53 showed a positive interim PET scan and of these only 13 (24.5%) achieved continuous complete remission (CCR), whereas 251 patients showed a negative PET scan and of these 231 (92%) achieved CCR. Comparison between interim PET-positive and interim PET-negative patients indicated a significant association between PET findings and 9-year progression-free survival and 9-year overall survival, with a median follow-up of 31 months. Among the early-stage patients, 19 had a positive interim PET scan and only 4 (21%) achieved CCR; among the 128 patients with a negative interim PET scan, 122 (97.6%) achieved CCR. Among the advanced-stage patients, 34 showed a persistently positive PET scan with only 9 (26.4%) achieving CCR, whereas 123 showed a negative interim PET scan with 109 (88.6%) achieving CCR., Conclusion: Our results demonstrate the role of an early PET scan as a significant step forward in the management of patients with early-stage or advanced-stage HL.

Positron emission tomography (PET) is a sectional molecular imaging procedure that allows evaluation of the metabolism at a molecular and cellular level. For a PET scan, the patient is injected with a radiotracer, such as (18)F-fluorodeoxyglucose (FDG). FDG PET-computed tomography has become an established modality for metabolic staging and plays an important role in the major steps of evaluation and treatment of most lymphoma subtypes, with significant impact in the initial staging, posttherapy evaluation, and suspect of relapse of disease. However, whenever the information of PET results is translated to changing treatment, especially in cases of further treatment, biopsy confirmation should always be made when possible., (Copyright © 2012 Elsevier Inc. All rights reserved.)

(18)F-FDG-PET is a well established standard procedure for most lymphoma subtypes. In particular the advantage of metabolic imaging stands in its strong predictivity in response. Indeed PET scan has been incorporated into revised response criteria for aggressive lymphomas and recommended to be performed at baseline and after therapy. At the same time, several ongoing clinical trials are investigating the value of treatment adaptation based on interim PET (PETi) results for Hodgkin Lymphoma (HL) and aggressive Non-Hodgkin Lymphoma (NHL). On the other hand, scientific literature provides limited detailed information regarding the numerous non aggressive NHL subtypes. Usually indolent NHL are typically less FDG avid, furthermore their long natural history and high incidence of recurrence decreases the clinical impact of a potential risk-adapted or response-adapted approach. We reviewed, from a nuclear medicine point of view and a clinical point of interest, evidence for the use of FDG-PET in monitoring early and end treatment response.

Introduction: Two hundred ten patients with newly diagnosed Hodgkin's lymphoma (HL) were consecutively enrolled in this prospective trial to evaluate the cost-effectiveness of fluorine-18 ((18)F)-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) scan in initial staging of patients with HL., Methods: All 210 patients were staged with conventional clinical staging (CCS) methods, including computed tomography (CT), bone marrow biopsy (BMB), and laboratory tests. Patients were also submitted to metabolic staging (MS) with whole-body FDG-PET scan before the beginning of treatment. A standard of reference for staging was determined with all staging procedures, histologic examination, and follow-up examinations. The accuracy of the CCS was compared with the MS. Local unit costs of procedures and tests were evaluated. Incremental cost-effectiveness ratio (ICER) was calculated for both strategies., Results: In the 210 patients with HL, the sensitivity for initial staging of FDG-PET was higher than that of CT and BMB in initial staging (97.9% vs. 87.3%; P < .001 and 94.2% vs. 71.4%, P < 0.003, respectively). The incorporation of FDG-PET in the staging procedure upstaged disease in 50 (24%) patients and downstaged disease in 17 (8%) patients. Changes in treatment would be seen in 32 (15%) patients. Cumulative cost for staging procedures was $3751/patient for CCS compared to $5081 for CCS + PET and $4588 for PET/CT. The ICER of PET/CT strategy was $16,215 per patient with modified treatment. PET/CT costs at the beginning and end of treatment would increase total costs of HL staging and first-line treatment by only 2%., Conclusion: FDG-PET is more accurate than CT and BMB in HL staging. Given observed probabilities, FDG-PET is highly cost-effective in the public health care program in Brazil., (Copyright © 2011. Published by Elsevier Inc.)

The optimal treatment of patients with locally advanced pancreatic cancer remains to be elucidated. Chemo-radiotherapy is regarded as the treatment of choice, and studies have examined the sequential schedule of induction chemoradiotherapy followed by chemoradiotherapy, with favourable results. This study investigated the principal clinical trials of chemoradiotherapy treatment in locally advanced pancreatic cancer in 2 patients. The 2 patients received induction chemotherapy with gemcitabine 1000 mg/mq day on days 1 and 8 of a 21-day cycle for two cycles, followed by chemoradiotherapy with concurrent radiosensitizer bi-weekly gemcitabine 50 mg/mq for six weeks. Radiotherapy consisted of an external conformational 3D treatment administered to the pancreatic bed and locoregional nodes, with a total dose of 4500 Gy fractionated in 180 Gy/day, and a boost of 900 Gy to the neoplastic mass. Efficacy was evaluated four weeks after the end of treatment by a computed tomography (CT) scan and by fluorodeoxyglucose positron-emission tomography/CT. The patients underwent further treatment with periodical instrumental evaluation. A disease control rate was observed in the two patients following sequential treatment, enhanced by subsequent treatment. The two patients remained alive 23-24 months following the diagnosis. The sequential treatment schedule therefore was an effective option in our locally advanced pancreatic cancer patients. A phase III trial and further investigation are required to verify this option in clinical practice.

We examined for myocardial ischemia induced by continuous inhalation of fenoterol in children with severe acute asthma. Thirty children with severe acute asthma were evaluated for signs of myocardial ischemia when treated with 0.5 mg kg dose (maximum 15 mg) of inhaled fenoterol for one hour. The heart rate was measured before and after inhalation. Cardiac enzymes (creatine kinase, creatine kinase MB fraction and troponin levels) were measured at admission and 12 hours later. An EKG was recorded before inhalation was started and immediately after its completion to detect the presence of any evidence of myocardial ischemia. All patients developed significant increase in heart rate. Six patients showed EKG changes compatible with myocardial ischemia, despite normal enzyme levels. Patients with severe acute asthma show tachycardia and may show EKG changes of myocardial ischemia.

Tumour necrosis factor-alpha (TNF-alpha) is a monocyte (MO)-derived cytokine that plays an essential role in the immunological system. In the present study our aim was to evaluate the levels of TNF-alpha secreted by MO from cancer patients. Blood MO were obtained from 10 lung cancer patients (LCP), 10 colorectal cancer patients (CCP) and 10 healthy donors (HD). TNF-alpha levels in MO culture supernatants spontaneously (sp) secreted or after stimulation with LPS treatment were evaluated using a commercial ELISA kit (sensibility: 10-1000 pg/ml). Mean values, expressed as pg/ml were: LCP: sp= 452.6+/-107.2, LPS= 589.5+/-126.7); CCP: sp= 84.1+/-25.0, LPS= 437.3+/-93.2; HD: sp= 74.2+/-21.5, LPS= 573.5+/-87.1. We concluded that MO from LCP secrete high levels of TNF-alpha spontaneously (p< 0.003 versus HD) and it was also observed an absence of response to LPS treatment in the 33% of the cases in these patients.

We studied the production of interleukin-1 (IL-1) by peripheral blood monocytes (Mo) from twelve normal subjects (NS) and eight and nine untreated lung and colorectal cancer patients (CP), respectively. No significant changes of extracellular IL-1 biological activity was observed between CP and NS by thymocyte proliferation assay. This result was independent that the cells were treated or not with lipopolisaccharide from E. coli (LPS, 10 micrograms/ml). Moreover, CP present normal amount of antigenic IL-1 beta in LPS treated Mo culture supernatants by enzyme-linked immunosorbent assay (ELISA). The biological activity of IL-1 released was not significant modified after indomethacin (Indo, 10(-6)M) and LPS + Indo treatments. Furthermore, patients showed a low percentage of LPS activated Mo with intracytoplasmatic IL-1 (alpha + beta) compared to normal values. These results were obtained by immuno-alkaline phosphatase staining using monoclonal antibody anti IL-1 (alpha + beta). In conclusion, CP had a reduced number of Mo with intracytoplasmatic IL-1 (alpha + beta) and the difference observed may depend on degradation or in the rate of synthesis of this cytokine.

We describe the cloning and expression of a new cDNA from the filamentous fungus Aspergillus clavatus IFO 8605. This cDNA contains an open reading frame (ORF) that predicts a putative ribonuclease precursor with high similarity to the alpha-sarcin family of ribosome-inactivating proteins (RIPs). The cDNA encoding the mature protein was expressed in Escherichia coli, and the recombinant protein, a 17-kDa polypeptide designated clavin was purified and characterized. Clavin shows typical type-1 RIP properties: specific cleavage of ribosomal and synthetic RNA and inhibition of protein synthesis in cell-free and cellular systems. When selectively targeted to a tumour cell antigen by coupling to a monoclonal antibody (mAb) clavin was able to inhibit protein synthesis at nanomolar concentration. Pharmacokinetics analysis in mice indicated an elimination half-life (t1/2 beta) of 7.4 h with no particular accumulation in major organs. Liver toxicity was very limited and transient while no alteration of kidney function was observed. Clavin induced a late and very low antibody response in mice. The in vitro and in vivo biological characteristics of clavin, together with its availability in large amounts, suggest the usefulness of this toxin in the production of toxic chemical conjugates.

Postoperative nausea and vomiting (PONV) are among the most common complications in surgical patients. In this prospective, double blind, parallel group study we compare the prophylactic antiemetic efficacy of ondansetron versus placebo in 90 patients undergoing general balanced anaesthesia. The patients were stratified according to the kind of surgery and randomly allocated to three treatment groups: 30 patients (Group A) received ondansetron 4 mg i.v. 1 hour before the induction of anaesthesia and placebo 1 hour before the end of surgery; 30 patients (Group B) received placebo 1 hour before the end of anaesthesia and ondansetron 4 mg i.v. 1 hour before the end of surgery; 30 patients (Group C-control group) received placebo in both the administrations. Data were analyzed by Student t test and chi 2 test; significance was taken at p < 0.05. The three groups proved comparable with respect to demographic characteristics, duration of anaesthesia and fentanyl consumption. Analysis of the results showed that PONV had a significantly lower incidence in treated patients (Groups A and B) than in the control group patients (Group C): postoperative nausea occurred in 13%, 30% and 67% of patients in Group A, B and C respectively and it was associated with vomiting in 3%, 7% and 57% of patients in Group A, B and C respectively. Although the patients in Group A showed a lower incidence of PONV in comparison to the patients in Group B, such differences proved to be not statistically significant. No adverse effects in relation to drug administration were observed. We conclude that ondansetron 4 mg i.v. is safe and effective in preventing PONV in the surgical patients, particularly when administered before the induction of anaesthesia.

The term "pre-emptive analgesia" implies the hypothesis that an analgesic treatment, given before nociceptive stimuli reach the Central Nervous System, could prevent or reduce the subsequent pain. The rational basis of this phenomenon, giving rise to much interest in the last years, comes from the finding that noxious stimuli cause wind-up and receptive fields expansion phenomena in the dorsal horn neurons of the spinal cord leading to hyperalgesia. Recently, many clinical trials to verify the existence of a pre-emptive effect regarding the management of postoperative pain by the administration of non steroidal antiinflammatory drugs (NSAIDs), local anesthetics and opioids have been conducted. As regards NSAIDs to date no study demonstrated a pre-emptive effect. Conflicting results emerged from trials employing local anesthetics, opioids or associations of the three classes of drugs. Thus, the "pre-emptive analgesia" represents a very important phenomenon for the basic research, but further trials must investigate its clinical impact.

The clinical use of the patient-controlled analgesia (PCA) represents a further improvement in the treatment of post-operative pain. In this way in success due to inadequate protocols, unpredictability of the drug absorption and variability of the response to one drug or to the same pain patterns between patients can be avoided. This technique allows the patient himself to control the pain without depending upon nurses or physicians for the administration of analgesic drugs. Although the PCA is in use since several years, there are still some unresolved problems which are considered in this paper.