Donanemab, another anti-Alzheimer's drug with risk and uncertain benefit.

Based on "reducing amyloid plaques in the brain", the U.S. Food and Drug Administration has granted accelerated and full approval for two monoclonal anti-Alzheimer's antibodies, aducanumab and lecanemab, respectively. Approval of a third antibody, donanemab, is pending. Moreover, lecanemab and donanemab are claimed to cause delay in the cognitive decline that characterizes the disease. We believe that these findings are subject to misinterpretation and statistical bias. Donanemab is claimed to cause removal of up to 86% of cerebral amyloid and 36% delay in cognitive decline compared to placebo. In reality, these are very small changes on an absolute scale and arguably less than what can be achieved with cholinesterase inhibitor/memantine therapy. Moreover, the "removal" of amyloid, based on the reduced accumulation of amyloid-PET tracer, most likely also reflects therapy-related tissue damage. This would also correlate with the minimal clinical effect, the increased frequency of amyloid-related imaging abnormalities, and the accelerated loss of brain volume in treated compared to placebo patients observed with these antibodies. We recommend halting approvals of anti-AD antibodies until these issues are fully understood to ensure that antibody treatment does not cause more harm than benefit to patients.

[18F]FDG PET/CT for identifying the causes of fever of unknown origin (FUO).

Fever of unknown origin (FUO) continues to be a challenging diagnosis in clinical medicine. It has more than 200 known causes, including infections, autoimmune diseases, neoplasia, and other miscellaneous disorders. Despite the development of a wide range of diagnostic tools, a specific diagnostic algorithm for FUO is not yet available. However, [18F]FDG PET/CT, which yields information on cellular metabolism, in addition to details of organ anatomy, has been shown to be successful in the FUO investigation. This study highlights the uses of [18F]FDG PET/CT in diagnosing various causes of FUO. [18F]FDG PET/CT has been increasingly used to detect septic infections, sterile inflammatory processes, and malignancies, occupying a significant portion of the known causes of FUO. It has led to a more definitive identification of the etiology of FUO and accurate clinical management. However, more in-depth studies are crucial to understanding if [18F]FDG PET/CT can be used in the work-up of FUO.

Central nervous system manifestations following vaccination against COVID-19.

Coronavirus disease 2019 (COVID-19) vaccination has become the most effective countermeasure in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, vaccination is associated with side effects. This narrative review focuses on central nervous system (CNS) manifestations following COVID-19 vaccination and provides a summary of the potential underlying mechanisms and methods of diagnosis and management of the vaccination-related CNS manifestations. Headache, myalgia, optic neuritis, seizure, multiple sclerosis, acute disseminated encephalomyelitis and encephalitis, delirium, acute transverse myelitis, and stroke have been reported after COVID-19 vaccination. Constant headache and myalgia are common manifestations that may necessitate further clinical investigation for stroke. To limit consequences, it is imperative to follow standard treatment protocols for each neurological disorder following COVID-19 vaccination. Immunosuppressive medication can be helpful in the treatment of seizures following vaccination since the immune response is involved in their etiology. Clinicians should be aware of the manifestations after COVID-19 vaccination to respond promptly and effectively. Clinical guidelines for the management of CNS manifestations following COVID-19 vaccination are in high demand and would be useful in each new SARS-CoV-2 variant pandemic.

The utility of PET imaging in depression.

This educational review article aims to discuss growing evidence from PET studies in the diagnosis and treatment of depression. PET has been used in depression to explore the neurotransmitters involved, the alterations in neuroreceptors, non-neuroreceptor targets (e.g., microglia and astrocytes), the severity and duration of the disease, the pharmacodynamics of various antidepressants, and neurobiological mechanisms of non-pharmacological therapies like psychotherapy, electroconvulsive therapy, and deep brain stimulation therapy, by showing changes in brain metabolism and receptor and non-receptor targets. Studies have revealed alterations in neurotransmitter systems such as serotonin, dopamine, GABA, and glutamate, which are linked to the pathophysiology of depression. Overall, PET imaging has furthered the neurobiological understanding of depression. Despite these advancements, PET findings have not yet led to significant changes in evidence-based practices. Addressing the reasons behind inconsistencies in PET imaging results, conducting large sample size studies with a more standardized methodological approach, and investigating further the genetic and neurobiological aspects of depression may better leverage PET imaging in future studies.

Alzheimer's Amyloid Hypothesis and Antibody Therapy: Melting Glaciers?

The amyloid cascade hypothesis for Alzheimer's disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis' claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration, while a third, donanemab, is under review. The main argument for the FDA approvals is a presumed therapy-induced removal of cerebral amyloid deposits. Lecanemab and donanemab are also thought to cause some statistical delay in the determination of cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of amyloid-positive trial patients with non-specific amyloid-PET imaging, and uncertain therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer's antibody therapy and hence on the amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of therapy on the brain.

Role of PET/CT in diagnosing and monitoring disease activity in rheumatoid arthritis: a review.

Rheumatoid Arthritis (RA) is a systemic inflammatory disorder that commonly presents with polyarthritis but can have multisystemic involvement and complications, leading to increased morbidity and mortality. The diagnosis of RA continues to be challenging due to its varied clinical presentations. In this review article, we aim to determine the potential of PET/CT to assist in the diagnosis of RA and its complications, evaluate the therapeutic response to treatment, and predict RA remission. PET/CT has increasingly been used in the last decade to diagnose, monitor treatment response, predict remissions, and diagnose subclinical complications in RA. PET imaging with [18F]-fluorodeoxyglucose ([18F]-FDG) is the most commonly applied radiotracer in RA, but other tracers are also being studied. PET/CT with [18F]-FDG, [18F]-NaF, and other tracers might lead to early identification of RA and timely evidence-based clinical management, decreasing morbidity and mortality. Although PET/CT has been evolving as a promising tool for evaluating and managing RA, more evidence is required before incorporating PET/CT in the standard clinical management of RA.

Imaging of Rotator Cuff Calcific Tendinopathy Using 18 F-NaF and 18 F-FDG PET/CT.

ABSTRACT: Calcific tendinopathy is a common condition of the shoulder caused by the inflammation and deposition of hydroxyapatite crystals in the rotator cuff tendons. PET tracers capturing the molecular changes associated with the crystal deposition of calcific tendinopathy remain underinvestigated. In this report, we present calcified tendinopathy of the infraspinatus tendon demonstrating both 18 F-NaF and 18 F-FDG focal uptake in a 61-year-old woman.

Revision of Alzheimer's diagnostic criteria or relocation of the Potemkin village.

The recently announced revision of the Alzheimer's disease (AD) diagnostic ATN classification adds to an already existing disregard for clinical assessment the rejection of image-based in vivo assessment of the brain's condition. The revision suggests that the diagnosis of AD should be based solely on the presence of cerebral amyloid-beta and tau, indicated by the "A" and "T". The "N", which stands for neurodegeneration - detected by imaging - should no longer be given importance, except that A+ ± T + = AD with amyloid PET being the main method for demonstrating A+ . We believe this is an artificial and misleading suggestion. It is artificial because it relies on biomarkers whose significance remains obscure and where the detection of "A" is based on a never-validated PET method using a tracer that marks much more than amyloid-beta. It is misleading because many patients without dementia will be falsely classified as having AD, but nonetheless candidates for passive immunotherapy, which may be more harmful than beneficial, and sometimes fatal.

Advancements in dendritic cell vaccination: enhancing efficacy and optimizing combinatorial strategies for the treatment of glioblastoma.

Glioblastomas (GBM) are highly invasive, malignant primary brain tumors. The overall prognosis is poor, and management of GBMs remains a formidable challenge, necessitating novel therapeutic strategies such as dendritic cell vaccinations (DCVs). While many early clinical trials demonstrate an induction of an antitumoral immune response, outcomes are mixed and dependent on numerous factors that vary between trials. Optimization of DCVs is essential; the selection of GBM-specific antigens and the utilization of 18F-fludeoxyglucose Positron Emission Tomography (FDG-PET) may add significant value and ultimately improve outcomes for patients undergoing treatment for glioblastoma. This review provides an overview of the mechanism of DCV, assesses previous clinical trials, and discusses future strategies for the integration of DCV into glioblastoma treatment protocols. To conclude, the review discusses challenges associated with the use of DCVs and highlights the potential of integrating DCV with standard therapies.

Utility of a simplified [18F] sodium fluoride PET imaging method to quantify bone metabolic flux for a wide range of clinical applications.

We review the rationale, methodology, and clinical utility of quantitative [18F] sodium fluoride ([18F]NaF) positron emission tomography-computed tomography (PET-CT) imaging to measure bone metabolic flux (Ki, also known as bone plasma clearance), a measurement indicative of the local rate of bone formation at the chosen region of interest. We review the bone remodelling cycle and explain what aspects of bone remodelling are addressed by [18F]NaF PET-CT. We explain how the technique works, what measurements are involved, and what makes [18F]NaF PET-CT a useful tool for the study of bone remodelling. We discuss how these measurements can be simplified without loss of accuracy to make the technique more accessible. Finally, we briefly review some key clinical applications and discuss the potential for future developments. We hope that the simplified method described here will assist in promoting the wider use of the technique.

Simultaneous Uptake of 18 F-NaF and 18 F-FDG by Bladder and Prostate Calculi.

ABSTRACT: Calcification and formation of calculi in the genitourinary system such as the bladder, kidney, and prostate are common processes of aging. Despite being in different parts of the body, these calculi can share risk factors; for instance, bladder and prostate calculi are seen in older men with benign prostatic hyperplasia. There have been increasing reports of detection of calculi using PET tracers such as 18 F-NaF and 18 F-FDG, suggesting their role for detection of extraosseous calcification. In this report, we present simultaneous detection of bladder and prostate calculi with both 18 F-NaF and 18 F-FDG avidity in a 74-year-old man with multiple myeloma.

Aging and Cerebral Glucose Metabolism: 18F-FDG-PET/CT Reveals Distinct Global and Regional Metabolic Changes in Healthy Patients.

Alterations in cerebral glucose metabolism can be indicative of both normal and pathological aging processes. In this retrospective study, we evaluated global and regional neurological glucose metabolism in 73 healthy individuals (mean age: 35.8 ± 13.1 years; 82.5% female) using 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). This population exhibited a low prevalence of comorbidities associated with cerebrovascular risk factors. We utilized 18F-FDG-PET/CT imaging and quantitative regional analysis to assess cerebral glucose metabolism. A statistically significant negative correlation was found between age and the global standardized uptake value mean (SUVmean) of FDG uptake (p = 0.000795), indicating a decrease in whole-brain glucose metabolism with aging. Furthermore, region-specific analysis identified significant correlations in four cerebral regions, with positive correlations in the basis pontis, cerebellar hemisphere, and cerebellum and a negative correlation in the lateral orbital gyrus. These results were further confirmed via linear regression analysis. Our findings reveal a nuanced understanding of how aging affects glucose metabolism in the brain, providing insight into normal neurology. The study underscores the utility of 18F-FDG-PET/CT as a sensitive tool in monitoring these metabolic changes, highlighting its potential for the early detection of neurological diseases and disorders related to aging.

Bilateral Carotid Artery Molecular Calcification Assessed by [18F] Fluoride PET/CT: Correlation with Cardiovascular and Thromboembolic Risk Factors.

Atherosclerosis, a leading cause of mortality and morbidity worldwide, involves inflammatory processes that result in plaque formation and calcification. The early detection of the molecular changes underlying these processes is crucial for effective disease management. This study utilized positron emission tomography/computed tomography (PET/CT) with [18F] sodium fluoride (NaF) as a tracer to visualize active calcification and inflammation at the molecular level. Our aim was to investigate the association between cardiovascular risk factors and [18F] NaF uptake in the left and right common carotid arteries (LCC and RCC). A cohort of 102 subjects, comprising both at-risk individuals and healthy controls, underwent [18F] NaF PET/CT imaging. The results revealed significant correlations between [18F] NaF uptake and cardiovascular risk factors such as age (ß = 0.005, 95% CI 0.003-0.008, p < 0.01 in LCC and ß = 0.006, 95% CI 0.004-0.009, p < 0.01 in RCC), male gender (ß = -0.08, 95% CI -0.173--0.002, p = 0.04 in LCC and ß = -0.13, 95% CI -0.21--0.06, p < 0.01 in RCC), BMI (ß = 0.02, 95% CI 0.01-0.03, p < 0.01 in LCC and ß = 0.02, 95% CI 0.01-0.03, p < 0.01 in RCC), fibrinogen (ß = 0.006, 95% CI 0.0009-0.01, p = 0.02 in LCC and ß = 0.005, 95% CI 0.001-0.01, p = 0.01), HDL cholesterol (ß = 0.13, 95% CI 0.04-0.21, p < 0.01 in RCC only), and CRP (ß = -0.01, 95% CI -0.02-0.001, p = 0.03 in RCC only). Subjects at risk showed a higher [18F] NaF uptake compared to healthy controls (one-way ANOVA; p = 0.02 in LCC and p = 0.04 in RCC), and uptake increased with estimated cardiovascular risk (one-way ANOVA, p < 0.01 in LCC only). These findings underscore the potential of [18F] NaF PET/CT as a sensitive tool for the early detection of atherosclerotic plaque, assessment of cardiovascular risk, and monitoring of disease progression. Further research is needed to validate the technique's predictive value and its potential impact on clinical outcomes.

The Role of FDG-PET in the Evaluation of Hidradenitis Suppurativa: A Systematic Review.

Hidradenitis suppurativa (HS) is a chronic skin disorder characterized by nodules, comedones, and sinus tracts that often leave prominent scarring. In recent years, non-invasive imaging techniques have been used to assess the inflammatory activity, vascularization, and treatment response of lesions. Specifically, fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans may aid in identifying systemic inflammation in patients with HS, improving diagnosis. Inflamed hypermetabolic tissues exhibit a greater uptake of FDG due to increased glucose uptake and vascularity. A systematic review was conducted to summarize the utility of nuclear imaging techniques in the diagnosis and treatment follow-up of HS. PubMed, Scopus, and ScienceDirect databases were utilized for relevant articles discussing the utility of PET scans in managing HS. A total of 51 citations were identified in the initial search. Following the review of titles, abstracts, and duplicates, 43 articles were excluded, leaving a total of eight articles for analysis. Data were extracted from each article, encompassing the number of patients, imaging techniques employed, and final results. An analysis of the data demonstrated that FDG-PET showed evidence of identifying subclinical lesions of the disease, improving the visualization of HS, and providing an objective method of assessing severity.

Novel technique of detecting inflammatory and osseous changes in the glenohumeral joint associated with patient age and weight using FDG- and NaF-PET imaging.

OBJECTIVE: The glenohumeral (GH) joint is a classic ball-and-socket joint of the shoulder subject to various pathologies including osteoarthritis (OA). Degenerative changes of the OA evident on traditional imaging are proceeded by molecular changes, which if detected early could enhance disease prevention and treatment. In this study, we use 18F-FluoroDeoxyGlucose (FDG) and 18F-sodium-fluoride (NaF)-PET/CT to investigate the effects limb laterality, age, and BMI on the inflammation and bone turnover of the GH shoulder joint. METHODS: FDG and NaF-PET/CT scans of 41 females (mean age of 43.9 ± 14.2 years) and 45 males (mean age of 44.5 ± 13.8 years) were analyzed with a semi-quantitative technique based on predefined region of interest. RESULTS: There was greater FDG uptake in the left side of the GH joint compared to the right in both females (left: 0.79 ± 0.17, right: 0.71 ± 0.2; P < 0.0001) and males (left: 0.76 ± 0.19, right: 0.57 ± 0.18; P < 0.0001). We also observed a strong positive association between BMI and FDG uptakes in females (left: P < 0.0001, r = 0.71, right: P < 0.0001, r = 0.58) and males (left: P < 0.0001, r = 0.56, right: P < 0.0001, r = 0.64). Association between BMI and NaF uptake were found in males as well (left: P = 0.004, r = 0.42, right: P = 0.02, r = 0.35). CONCLUSION: Our study demonstrates the varying effect of limb laterality and BMI on FDG and NaF uptake at the GH joint. Adoption of molecular imaging will require future studies that correlate tracer uptake with relevant medical and illness history as well as degenerative change evident on traditional imaging.

Update on Positron Emission Tomography/Magnetic Resonance Imaging: Cancer and Inflammation Imaging in the Clinic.

Hybrid PET/MRI is highly valuable, having made significant strides in overcoming technical challenges and offering unique advantages such as reduced radiation, precise data coregistration, and motion correction. Growing evidence highlights the value of PET/MRI in broad clinical aspects, including inflammatory and oncological imaging in adults, pregnant women, and pediatrics, potentially surpassing PET/CT. This newly integrated solution may be preferred over PET/CT in many clinical conditions. However, further technological advancements are required to facilitate its broader adoption as a routine diagnostic modality.

Brain MRI findings in neurologically symptomatic COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been associated with nervous system involvement, with more than one-third of COVID-19 patients experiencing neurological manifestations. Utilizing a systematic review, this study aims to summarize brain MRI findings in COVID-19 patients presenting with neurological symptoms. METHODS: Systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist. The electronic databases of PubMed/MEDLINE, Embase, Scopus, and Web of Science were systematically searched for literature addressing brain MRI findings in COVID-19 patients with neurological symptoms. RESULTS: 25 publications containing a total number of 3118 COVID-19 patients with neurological symptoms who underwent MRI were included. The most common MRI findings and the respective pooled incidences in decreasing order were acute/subacute infarct (22%), olfactory bulb abnormalities (22%), white matter abnormalities (20%), cerebral microbleeds (17%), grey matter abnormalities (12%), leptomeningeal enhancement (10%), ADEM (Acute Disseminated Encephalomyelitis) or ADEM-like lesions (10%), non-traumatic ICH (10%), cranial neuropathy (8%), cortical gray matter signal changes compatible with encephalitis (8%), basal ganglia abnormalities (5%), PRES (Posterior Reversible Encephalopathy Syndrome) (3%), hypoxic-ischemic lesions (4%), venous thrombosis (2%), and cytotoxic lesions of the corpus callosum (2%). CONCLUSION: The present study revealed that a considerable proportion of patients with COVID-19 might harbor neurological abnormalities detectable by MRI. Among various findings, the most common MRI alterations are acute/subacute infarction, olfactory bulb abnormalities, white matter abnormalities, and cerebral microbleeds.