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European Journal of Neurology Feb 2024Our aim is to review the most recent evidence on novel antibody therapies for Alzheimer's disease directed against amyloid-β. This is a joint statement of the European... (Review)
Review
Our aim is to review the most recent evidence on novel antibody therapies for Alzheimer's disease directed against amyloid-β. This is a joint statement of the European Association of Neurology and the European Psychiatric Association. After numerous unsuccessful endeavors to create a disease-modifying therapy for Alzheimer's disease, substantial and consistent evidence supporting the clinical effectiveness of monoclonal antibodies aimed at amyloid-β is finally emerging. The latest trials not only achieved their primary objective of slowing the progression of the disease over several months but also demonstrated positive secondary clinical outcomes and a decrease in amyloid-β levels as observed through positron emission tomography scans. Taken as a whole, these findings mark a significant breakthrough by substantiating that reducing amyloid-β yields tangible clinical benefits, beyond mere changes in biomarkers. Concurrently, the regular utilization of the new generation of drugs will determine whether statistical efficacy translates into clinically meaningful improvements. This may well signify the dawning of a new era in the development of drugs for Alzheimer's disease.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Treatment Outcome; Antibodies, Monoclonal; Positron-Emission Tomography; Cognitive Dysfunction; Biomarkers
PubMed: 37697714
DOI: 10.1111/ene.16049 -
Molecular Psychiatry Oct 2023Dementia is a leading cause of disability and death worldwide. At present there is no disease modifying treatment for any of the most common types of dementia such as... (Review)
Review
Dementia is a leading cause of disability and death worldwide. At present there is no disease modifying treatment for any of the most common types of dementia such as Alzheimer's disease (AD), Vascular dementia, Lewy Body Dementia (LBD) and Frontotemporal dementia (FTD). Early and accurate diagnosis of dementia subtype is critical to improving clinical care and developing better treatments. Structural and molecular imaging has contributed to a better understanding of the pathophysiology of neurodegenerative dementias and is increasingly being adopted into clinical practice for early and accurate diagnosis. In this review we summarise the contribution imaging has made with particular focus on multimodal magnetic resonance imaging (MRI) and positron emission tomography imaging (PET). Structural MRI is widely used in clinical practice and can help exclude reversible causes of memory problems but has relatively low sensitivity for the early and differential diagnosis of dementia subtypes. F-fluorodeoxyglucose PET has high sensitivity and specificity for AD and FTD, while PET with ligands for amyloid and tau can improve the differential diagnosis of AD and non-AD dementias, including recognition at prodromal stages. Dopaminergic imaging can assist with the diagnosis of LBD. The lack of a validated tracer for α-synuclein or TAR DNA-binding protein 43 (TDP-43) imaging remain notable gaps, though work is ongoing. Emerging PET tracers such as C-UCB-J for synaptic imaging may be sensitive early markers but overall larger longitudinal multi-centre cross diagnostic imaging studies are needed.
Topics: Humans; Frontotemporal Dementia; Diagnosis, Differential; Alzheimer Disease; Lewy Body Disease; Neuroimaging; Positron-Emission Tomography
PubMed: 37608222
DOI: 10.1038/s41380-023-02215-8 -
The British Journal of Radiology Aug 2023Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer deaths in both sexes combined. Recent years have seen major advances in the diagnostic... (Review)
Review
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer deaths in both sexes combined. Recent years have seen major advances in the diagnostic and treatment options for patients with non-small-cell lung cancer (NSCLC), including the routine use of 2-deoxy-2[F]-fluoro-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) in staging and response evaluation, minimally invasive endoscopic biopsy, targeted radiotherapy, minimally invasive surgery, and molecular and immunotherapies. In this review, the central roles of CT and F-FDG PET/CT in staging and response in both NSCLC and malignant pleural mesothelioma (MPM) are critically assessed. The Tumour Node Metastases (TNM-8) staging systems for NSCLC and MPM are presented with critical appraisal of the strengths and pitfalls of imaging. Overviews of the Response Evaluation Criteria in Solid Tumours (RECIST 1.1) for NSCLC and the modified RECIST criteria for MPM are provided, together with discussion of the benefits and limitations of these anatomical-based tools. Metabolic response assessment (not evaluated by RECIST 1.1) will be explored. We introduce the Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST 1.0) to include its advantages and challenges. The limitations of both anatomical and metabolic assessment criteria when applied to NSCLC treated with immunotherapy and the important concept of pseudoprogression are addressed with reference to immune RECIST (iRECIST). Separate consideration is given to the diagnosis and follow up of solitary pulmonary nodules with reference to the British Thoracic Society guidelines and Fleischner guidelines and use of the Brock (CT-based) and Herder (addition of F-FDG PET/CT) models for assessing malignant potential. We discuss how these models inform decisions by the multidisciplinary team, including referral of suspicious nodules for non-surgical management in patients unsuitable for surgery. We briefly outline current lung screening systems being used in the UK, Europe and North America. Emerging roles for MRI in lung cancer imaging are reviewed. The use of whole-body MRI in diagnosing and staging NSCLC is discussed with reference to the recent multicentre trial. The potential use of diffusion-weighted MRI to distinguish tumour from radiotherapy-induced lung toxicity is discussed. We briefly summarise the new PET-CT radiotracers being developed to evaluate specific aspects of cancer biology, other than glucose uptake. Finally, we describe how CT, MRI and F-FDG PET/CT are moving from primarily diagnostic tools for lung cancer towards having utility in prognostication and personalised medicine with the agency of artificial intelligence.
Topics: Male; Female; Humans; Lung Neoplasms; Positron Emission Tomography Computed Tomography; Carcinoma, Non-Small-Cell Lung; Fluorodeoxyglucose F18; Artificial Intelligence; Radiopharmaceuticals; Positron-Emission Tomography; Magnetic Resonance Imaging; Neoplasm Staging
PubMed: 37097296
DOI: 10.1259/bjr.20220339 -
Radiologia Oct 2023Chronic expansive hematoma (CEH) is a rare lesion, characterized by the persistence and increase in size of an hematoma for a period greater than one month since the...
Chronic expansive hematoma (CEH) is a rare lesion, characterized by the persistence and increase in size of an hematoma for a period greater than one month since the initial hemorrhage. The clinical importance of this pathology is due to the fact that it can simulate malignant soft tissue neoplasms, both clinically as a result of its progressive growth and radiologically for its findings in imaging studies. This article will review three cases of CEH in different scenarios, explaining the radiological findings in different imaging techniques such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and PET-CT.
Topics: Humans; Hematoma; Magnetic Resonance Imaging; Positron Emission Tomography Computed Tomography; Tomography, X-Ray Computed
PubMed: 37858357
DOI: 10.1016/j.rxeng.2023.09.006 -
Endocrine Reviews May 2024Pheochromocytomas/paragangliomas are unique in their highly variable molecular landscape driven by genetic alterations, either germline or somatic. These mutations... (Review)
Review
Pheochromocytomas/paragangliomas are unique in their highly variable molecular landscape driven by genetic alterations, either germline or somatic. These mutations translate into different clusters with distinct tumor locations, biochemical/metabolomic features, tumor cell characteristics (eg, receptors, transporters), and disease course. Such tumor heterogeneity calls for different imaging strategies in order to provide proper diagnosis and follow-up. This also warrants selection of the most appropriate and locally available imaging modalities tailored to an individual patient based on consideration of many relevant factors including age, (anticipated) tumor location(s), size, and multifocality, underlying genotype, biochemical phenotype, chance of metastases, as well as the patient's personal preference and treatment goals. Anatomical imaging using computed tomography and magnetic resonance imaging and functional imaging using positron emission tomography and single photon emission computed tomography are currently a cornerstone in the evaluation of patients with pheochromocytomas/paragangliomas. In modern nuclear medicine practice, a multitude of radionuclides with relevance to diagnostic work-up and treatment planning (theranostics) is available, including radiolabeled metaiodobenzylguanidine, fluorodeoxyglucose, fluorodihydroxyphenylalanine, and somatostatin analogues. This review amalgamates up-to-date imaging guidelines, expert opinions, and recent discoveries. Based on the rich toolbox for anatomical and functional imaging that is currently available, we aim to define a customized approach in patients with (suspected) pheochromocytomas/paragangliomas from a practical clinical perspective. We provide imaging algorithms for different starting points for initial diagnostic work-up and course of the disease, including adrenal incidentaloma, established biochemical diagnosis, postsurgical follow-up, tumor screening in pathogenic variant carriers, staging and restaging of metastatic disease, theranostics, and response monitoring.
Topics: Humans; Pheochromocytoma; Adrenal Gland Neoplasms; Paraganglioma; Magnetic Resonance Imaging; Positron-Emission Tomography
PubMed: 38206185
DOI: 10.1210/endrev/bnae001 -
Neurobiology of Aging Sep 2023Amyloid staging models showed that regional abnormality occurs before global positivity. Several studies assumed that the trajectory of amyloid spread is homogeneous,...
Amyloid staging models showed that regional abnormality occurs before global positivity. Several studies assumed that the trajectory of amyloid spread is homogeneous, but clinical evidence suggests that it is highly heterogeneous. We tested whether different amyloid-β (Aβ) patterns exist by applying clustering on negative scans and investigating their demographics, clinical, cognitive, and biomarkers correlates, and cognitive trajectories. 151 individuals from Geneva and Zurich cohorts with T1-MRI, negative Aβ positron emission tomography (PET,centiloid<12) and clinical assessment were included. N=123 underwent tau PET, and N=65 follow-up neuropsychological assessment. We performed k-means clustering using 33 Aβ regional Standardized Uptake Vales ratio. Demographics, clinical, cognitive, and biomarkers differences were investigated. Longitudinal cognitive changes by baseline cluster status were estimated using a linear mixed model. The cluster analysis identified two clusters: temporal predominant (TP) and cingulate predominant (CP). TP tau deposition was higher than CP. A trend for a higher cognitive decline in TP compared to CP was observed. This study suggests the existence of two Aβ deposition patterns in the earliest phases of Aβ accumulation, differently prone to tau pathology and cognitive decline.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Amyloid; Positron-Emission Tomography; Cognitive Dysfunction; Biomarkers; tau Proteins
PubMed: 37279618
DOI: 10.1016/j.neurobiolaging.2023.05.006 -
European Urology Oct 2023Radiohybrid (rh) F-rhPSMA-7.3 is a novel high-affinity prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for prostate cancer (PCa) imaging.
Diagnostic Performance and Safety of Positron Emission Tomography with F-rhPSMA-7.3 in Patients with Newly Diagnosed Unfavourable Intermediate- to Very-high-risk Prostate Cancer: Results from a Phase 3, Prospective, Multicentre Study (LIGHTHOUSE).
BACKGROUND
Radiohybrid (rh) F-rhPSMA-7.3 is a novel high-affinity prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for prostate cancer (PCa) imaging.
OBJECTIVE
To evaluate the diagnostic performance and safety of F-rhPSMA-7.3 in newly diagnosed PCa patients planned for prostatectomy.
DESIGN, SETTING, AND PARTICIPANTS
Data on F-rhPSMA-7.3 were reported from the phase 3 prospective, multicentre LIGHTHOUSE study (NCT04186819).
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Patients underwent positron emission tomography/computed tomography (PET/CT) 50-70 min after an injection of 296 MBq F-rhPSMA-7.3. Images were interpreted locally and by three blinded independent readers. The coprimary endpoints were patient-level sensitivity and specificity for the detection of pelvic lymph node (PLN) metastases, validated using histopathology at PLN dissection. Prespecified statistical thresholds (lower bounds of 95% confidence interval [CI]) were set at 22.5% for sensitivity and 82.5% for specificity.
RESULTS AND LIMITATIONS
Of 372 patients screened, 352 had evaluable F-rhPSMA-7.3-PET/CT and 296 (99 [33%] with unfavourable intermediate-risk [UIR] and 197 [67%] with high-/very-high-risk [VHR] PCa) subsequently underwent surgery. As per the independent reads, 23-37 (7.8-13%) patients had F-rhPSMA-7.3-positive PLN. Seventy (24%) patients had one or more positive PLNs on histopathology. The sensitivity for PLN detection was 30% (95% CI, 19.6-42.1%) for reader 1, 27% (95% CI, 17.2-39.1%) for reader 2, and 23% (95% CI, 13.7-34.4%) for reader 3, not meeting the prespecified threshold. Specificity was 93% (95% CI, 88.8-95.9%), 94% (95% CI, 89.8-96.6%), and 97% (95% CI, 93.7-98.7%), respectively, exceeding the threshold for all readers. Specificity was high (≥92%) across both risk stratifications. Sensitivity was higher among high-risk/VHR (24-33%) than among UIR (16-21%) patients. Extrapelvic (M1) lesions were reported for 56-98/352 (16-28%) patients who underwent F-rhPSMA-7.3-PET/CT irrespective of surgery. Verification of these (predominantly by conventional imaging) gave a verified detection rate of 9.9-14% (positive predictive value, 51-63%). No serious adverse events were observed.
CONCLUSIONS
Across all risk stratifications, F-rhPSMA-7.3-PET/CT had high specificity, meeting the specificity endpoint. The sensitivity endpoint was not met, although higher sensitivity was noted among high-risk/VHR than among UIR patients. Overall, F-rhPSMA-7.3-PET/CT was well tolerated, and identified N1 and M1 disease prior to surgery in newly diagnosed PCa patients.
PATIENT SUMMARY
In order to select the most appropriate treatment for patients with prostate cancer, it is critical to diagnose the disease burden accurately at initial diagnosis. In this study, we investigated a new diagnostic imaging agent in a large population of men with primary prostate cancer. We found it to have an excellent safety profile and to provide clinically useful information regarding the presence of disease beyond the prostate.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Prospective Studies; Positron-Emission Tomography; Prostatic Neoplasms; Prostate; Gallium Radioisotopes
PubMed: 37414702
DOI: 10.1016/j.eururo.2023.06.018 -
Cancer Communications (London, England) Aug 2023The current standard of care for non-bulky diffuse large B-cell lymphoma (DLBCL) patients with an International Prognostic Index (IPI) of 0 is four cycles of rituximab... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The current standard of care for non-bulky diffuse large B-cell lymphoma (DLBCL) patients with an International Prognostic Index (IPI) of 0 is four cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) but whether the same efficacy can be achieved with reduced chemotherapy regimen of four cycles for non-bulky DLBCL patients with an IPI of 1 remains unclear. This study compared four cycles versus six cycles of chemotherapy in non-bulky low-risk DLBCL patients with negative interim positron emission tomography with computed tomography (PET-CT, Deauville 1-3), irrespective of age and other IPI risk factors (IPI 0-1).
METHODS
This was an open-label, randomized, phase III, non-inferiority trial. Patients aged 14-75 years with newly diagnosed low-risk DLBCL, according to IPI, achieving PET-CT confirmed complete response (CR) after four cycles of R-CHOP were randomized (1:1) between four cycles of rituximab (4R-CHOP+4R arm) or two cycles of R-CHOP plus two cycles of rituximab (6R-CHOP+2R arm). The primary endpoint was 2-year progression-free survival (PFS), conducted in the intention-to-treat population. Safety was assessed in patients with at least one cycle of assigned treatment. The non-inferiority margin was -8%.
RESULTS
A total of 287 patients were included in the intention-to-treat analysis, the median follow-up was 47.3 months, and the 2-year PFS rate was 95% (95% confidence interval [CI], 92% to 99%) and 94% (95% CI, 91% to 98%) for the 4R-CHOP+4R and 6R-CHOP+2R arm. The absolute difference in 2-year PFS between the two arms was 1% (95% CI, -5% to 7%), supporting the non-inferiority of 4R-CHOP+4R. Grade 3-4 neutropenia was lower in the last four cycles of rituximab alone in the 4R-CHOP+4R arm (16.7% versus 76.9%), with decreased risk of febrile neutropenia (0.0% versus 8.4%) and infection (2.1% versus 14.0%).
CONCLUSIONS
For newly diagnosed low-risk DLBCL patients, interim PET-CT after four cycles of R-CHOP was effective in identifying patients with Deauville 1-3 who would have a good response and Deauville 4-5 patients who might have high-risk biological features or develop resistance. Reducing the standard six cycles to four cycles of chemotherapy had comparable clinical efficacy and fewer adverse events in low-risk, non-bulky DLBCL with interim PET-CT confirmed CR.
Topics: Humans; Rituximab; Positron Emission Tomography Computed Tomography; Antibodies, Monoclonal, Murine-Derived; Disease-Free Survival; Lymphoma, Large B-Cell, Diffuse; Vincristine; Cyclophosphamide; Doxorubicin; Prednisone; Positron-Emission Tomography; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37403255
DOI: 10.1002/cac2.12462 -
The British Journal of Radiology Oct 2023Image reconstruction for positron emission tomography (PET) has been developed over many decades, with advances coming from improved modelling of the data statistics and... (Review)
Review
Image reconstruction for positron emission tomography (PET) has been developed over many decades, with advances coming from improved modelling of the data statistics and improved modelling of the imaging physics. However, high noise and limited spatial resolution have remained issues in PET imaging, and state-of-the-art PET reconstruction has started to exploit other medical imaging modalities (such as MRI) to assist in noise reduction and enhancement of PET's spatial resolution. Nonetheless, there is an ongoing drive towards not only improving image quality, but also reducing the injected radiation dose and reducing scanning times. While the arrival of new PET scanners (such as total body PET) is helping, there is always a need to improve reconstructed image quality due to the time and count limited imaging conditions. Artificial intelligence (AI) methods are now at the frontier of research for PET image reconstruction. While AI can learn the imaging physics as well as the noise in the data (when given sufficient examples), one of the most common uses of AI arises from exploiting databases of high-quality reference examples, to provide advanced noise compensation and resolution recovery. There are three main AI reconstruction approaches: (i) direct data-driven AI methods which rely on supervised learning from reference data, (ii) iterative (unrolled) methods which combine our physics and statistical models with AI learning from data, and (iii) methods which exploit AI with our known models, but crucially can offer benefits even in the absence of any example training data whatsoever. This article reviews these methods, considering opportunities and challenges of AI for PET reconstruction.
Topics: Humans; Artificial Intelligence; Image Processing, Computer-Assisted; Phantoms, Imaging; Positron-Emission Tomography; Algorithms
PubMed: 37486607
DOI: 10.1259/bjr.20230292 -
Cancer Imaging : the Official... Aug 2023F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) plays a crucial role in tumour diagnosis, staging, and therapy response evaluation... (Review)
Review
F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) plays a crucial role in tumour diagnosis, staging, and therapy response evaluation of various cancer types and has been a standard imaging modality used in clinical oncology practice for many years. However, it has certain limitations in evaluating some particular gastrointestinal cancer types due to low FDG-avidity or interphering physiological background activity. Fibroblast activation protein (FAP), a protein of the tumour microenvironment, is overexpressed in a wide range of cancers which makes it an attractive target for both tumour imaging and therapy. Recently, FAP-targeted radiopharmaceuticals are widely used in clinical research and achieved great results in tumour imaging. Considering the limitations of FDG PET/CT and the lack of physiological FAP-targeted tracer uptake in liver and intestinal loops, gastrointestinal cancers are among the most promising indications of FAP-targeted imaging. Herein, we present a comprehensive review of FAP-targeted imaging in gastrointestinal cancers in order to clarify the current and potential future role of this class of molecules in gastrointestinal oncology.
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Gastrointestinal Neoplasms; Positron-Emission Tomography; Liver; Tumor Microenvironment
PubMed: 37608378
DOI: 10.1186/s40644-023-00598-z