Clinical Application of ImmunoPET Targeting Checkpoint Inhibitors

In the last decade, monoclonal antibodies (mAbs) targeting CTLA-4, PD-1, or PD-L1 have been developed and immune checkpoint inhibitors (ICIs) have become the main approach in cancer immunotherapy. However, not all patients benefit from ICI therapy and some are at risk of developing treatment-induced side-effects. These aspects, in parallel with the imaging challenges related to response assessments during immunotherapy, have driven scientific research to the discovery of new predictive biomarkers to individualize patients who could benefit from ICIs. In this context, molecular imaging using PET (positron emission tomography), which allows for whole-body tumor visualization, may be a promising non-invasive method for the determination of patients’ sensitivity to antibody drugs. Several PET tracers, diverse from 2-[18F]FDG (or 2-Deoxy-2-[18F]fluoroglucose), have been developed to image immune checkpoints (ICs) or key elements of the immune system, although most of them are still in preclinical phases. Herein, we present the current state of the ImmunoPET-targeting of IC proteins with mAbs and antibody fragments, with a main focus on the latest developments in clinical molecular imaging studies of solid tumors. Moreover, given the relevance of the immune system and of tumor-infiltrating lymphocytes in particular in the prediction of the benefit of ICIs, we dedicate a portion of this review to ImmunoPET-targeting T cells

99mTc-EDDA/HYNIC-TOC is a new opportunity in Neuroendocrine Tumors of the Lung (and in other malignant and benign pulmonary diseases)

Neuroendocrine tumors (NETs) consist of a relatively rare spectrum of malignancies that can arise from neuroendocrine cells; lung NETs (L-NETs) represent about 25% of primary lung neoplasm and 10% of all carcinoid tumors. Diagnostic algorithm usually takes into consideration chest X-ray, contrast-enhanced CT and MRI. Nuclear medicine plays a crucial role in the detection and correct assessment of neoplastic functional status as it provides in vivo metabolic data related to the over-expression of Somatostatin Receptors (SSTRs) and also predicting response to peptide receptor radionuclide therapy (PRRT). 111In-Pentreotide (Octreoscan®) is commercially available for imaging of neuroendocrine tumors, their metastases and the management of patients with NETs. More recently, 99mTc-EDDA/HYNIC-TOC(Tektrotyd®) was introduced into the marketand its use has been approved for imaging of patients with L-NETs and other SSTR-positive tumors. 99mTc-EDDA/HYNIC-TOC could also represent a good alternative to 68Ga-DOTA-peptides (DOTA-TOC, DOTA-NOC, DOTA-TATE) in hospitals or centers where PET/CT or 68Ge/68Ga generators are not available. When compared to 111In-Pentetreotide, Tektrotyd® showed a slightly higher sensitivity, in presence of higher imaging quality and lower radiation exposure for patients. Interesting perspectives depending on the kinetic analysis allowed by Tektrotyd® may be obtained in differential diagnosis of non-small cells lung cancer (NSCLC) versus small cells lung cancer (SCLC) and NETs. An interesting perspective could be also associated with a surgery radioguided by Tektrotyd® in operable lung tumours, including either NETs and NSCLC

Diegesis and Mimesis

This Journal issue deals with the relation between diegesis and mimesis in drama and in genres which share aspects of drama, consciously and metatextually blending narrative and dialogue. It assumes that there exists a theoretical problem concerning different conceptions of these two notions, which derives from Plato\u2019s and Aristotle\u2019s different treatment of them and, today, by the opposite approaches shown by narratologists and theatre semioticians. The articles here collected do not discuss such theoretical questions. Instead, they examine the function of narration and dialogue within a selected number of significant examples foregrounding their generic, performative, and \u2018ideological\u2019 functions from the Antiquity to contemporaneity. The notion of mimesis as artistic representation is also questioned when theatre comes to interrogate the idea of counterfactuality vis-a-vis its power to construct and deconstruct our historical memories on stage. It is also explored in the context of postdramatic theatre when mimesis enters the field of a generative ontology eroding the concept itself of representation. In all cases, whether narrative on stage concerns messenger-speeches or other types of diegetic performances, diegesis is considered as a collaborative mode, rather than an antagonistic category in respect to mimetic dialogue. The introduction draws a synopsis of some of the main issues and theoretical questions currently debated by narratologists and semioticians alike, laying the ground for the following articles to explore the possibilities for a fruitful integration of diegesis and mimesis over time

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

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

Clinical Impact of 18F-FDG PET/CT in the Diagnostic Workup of Pancreatic Ductal Adenocarcinoma: A Systematic Review

In this review, the performance of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the diagnostic workup of pancreatic ductal adenocarcinoma (PDAC) is evaluated. A comprehensive literature search up to September 2020 was performed, selecting studies with the presence of: sample size >= 10 patients and index test (i.e., "FDG" or "18F-FDG" AND "pancreatic adenocarcinoma" or "pancreas cancer" AND "PET" or "positron emission tomography"). The methodological quality was evaluated using the revised quality assessment of diagnostic accuracy studies (QUADAS-2) tool and presented according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Basic data (authors, year of publication, country and study design), patients' characteristics (number of enrolled subjects and age), disease phase, type of treatment and grading were retrieved. Forty-six articles met the adopted research criteria. The articles were divided according to the considered clinical context. Namely, besides conventional anatomical imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), molecular imaging with FDG PET/CT is an important tool in PDAC, for all disease stages. Further prospective studies will be necessary to confirm the cost-effectiveness of such imaging techniques by testing its real potential improvement in the clinical management of PDAC

The Utility of Conventional Amino Acid PET Radiotracers in the Evaluation of Glioma Recurrence also in Comparison with MRI

Aim: In this comprehensive review we present an update on the most relevant studies evaluating the utility of amino acid PET radiotracers for the evaluation of glioma recurrence as compared to magnetic resonance imaging (MRI). Methods: A literature search extended until June 2020 on the PubMed/MEDLINE literature database was conducted using the terms “high-grade glioma”, “glioblastoma”, “brain tumors”, “positron emission tomography”, “PET”, “amino acid PET”, “[11C]methyl-l-methionine”, “[18F]fluoroethyl-tyrosine”, “[18F]fluoro-l-dihydroxy-phenylalanine”, “MET”, “FET”, “DOPA”, “magnetic resonance imaging”, “MRI”, “advanced MRI”, “magnetic resonance spectroscopy”, “perfusion-weighted imaging”, “diffusion-weighted imaging”, “MRS”, “PWI”, “DWI”, “hybrid PET/MR”, “glioma recurrence”, “pseudoprogression”, “PSP”, “treatment-related change”, and “radiation necrosis” alone and in combination. Only original articles edited in English and about humans with at least 10 patients were included. Results: Forty-four articles were finally selected. Conventional amino acid PET tracers were demonstrated to be reliable diagnostic techniques in differentiating tumor recurrence thanks to their high uptake from tumor tissue and low background in normal grey matter, giving additional and early information to standard modalities. Among them, MET–PET seems to present the highest diagnostic value but its use is limited to on-site cyclotron facilities. [18F]labelled amino acids, such as FDOPA and FET, were developed to provide a more suitable PET tracer for routine clinical applications, and demonstrated similar diagnostic performance. When compared to the gold standard MRI, amino acid PET provides complementary and comparable information to standard modalities and seems to represent an essential tool in the differentiation between tumor recurrence and other entities such as pseudoprogression, radiation necrosis, and pseudoresponse. Conclusions: Despite the introduction of new advanced imaging techniques, the diagnosis of glioma recurrence remains challenging. In this scenario, the growing knowledge about imaging techniques and analysis, such as the combined PET/MRI and the application of artificial intelligence (AI) and machine learning (ML), could represent promising tools to face this difficult and debated clinical issue

Characterization of Mediastinal Bulky Lymphomas with FDG-PET-Based Radiomics and Machine Learning Techniques

Background: This study tested the diagnostic value of 18F-FDG PET/CT (FDG-PET) volumetric and texture parameters in the histological differentiation of mediastinal bulky disease due to classical Hodgkin lymphoma (cHL), primary mediastinal B-cell lymphoma (PMBCL) and grey zone lymphoma (GZL), using machine learning techniques. Methods: We reviewed 80 cHL, 29 PMBCL and 8 GZL adult patients with mediastinal bulky disease and histopathological diagnoses who underwent FDG-PET pre-treatment. Volumetric and radiomic parameters were measured using FDG-PET both for bulky lesions (BL) and for all lesions (AL) using LIFEx software (threshold SUV ≥ 2.5). Binary and multiclass classifications were performed with various machine learning techniques fed by a relevant subset of radiomic features. Results: The analysis showed significant differences between the lymphoma groups in terms of SUVmax, SUVmean, MTV, TLG and several textural features of both first- and second-order grey level. Among machine learning classifiers, the tree-based ensembles achieved the best performance both for binary and multiclass classifications in histological differentiation. Conclusions: Our results support the value of metabolic heterogeneity as an imaging biomarker, and the use of radiomic features for early characterization of mediastinal bulky lymphoma