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Langerhans cell histiocytosis (LCH) is a complex disorder characterized by the clonal proliferation of Langerhans cells, primarily affecting children and adolescents. This condition exhibits a wide spectrum of clinical presentations, necessitating a multidisciplinary approach for diagnosis, treatment, and follow-up. Cutaneous manifestations of LCH are significant, mimicking common dermatoses and posing diagnostic challenges. [18F]Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) has emerged as an important tool in the evaluation of pediatric LCH, offering insights into disease activity, extent, and therapeutic response. Moreover, FDG-PET provides a non-invasive means to distinguish between active LCH skin lesions and other dermatological conditions with similar clinical appearances, enhancing diagnostic accuracy and aiding in disease monitoring. This educational review summarizes the utility of nuclear imaging techniques, with a focus on PET scans, in the diagnosis and management of cutaneous pediatric LCH. A comprehensive literature search identified seven relevant articles, including retrospective studies and case reports. These studies highlight the efficacy of FDG-PET in localizing active LCH skin lesions, monitoring disease activity, and guiding treatment decisions. FDG-PET represents a valuable imaging modality for dermatologists, oncologists, and pediatricians managing pediatric LCH patients with cutaneous involvement. This non-invasive technique contributes to improved diagnostic accuracy and facilitates early intervention, ultimately enhancing patient care and outcomes.

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.

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.

Cerebrovascular disease (CVD) is a global health concern, and early detection is crucial for effective intervention. This case report presents a 31-year-old male patient with multiple cardiac risk factors who underwent positron emission tomography/computed tomography (PET/CT) with 18F-sodium fluoride (NaF) and 18F-fluorodeoxyglucose (FDG) to evaluate for the presence and degree of atherosclerosis in the aorta, carotid arteries, coronary arteries, iliac arteries, and the femoral arteries. Elevated NaF uptake within the bilateral carotid arteries signified substantial ongoing vascular microcalcification. Reduced global brain metabolism and region-specific hypometabolism measured with FDG PET indicated potential cerebrovascular mechanisms that may be influencing neurological function. The findings highlight the potential of emerging PET tracers, such as NaF, to improve the diagnostic accuracy and therapeutic management of CVD. This case emphasizes the importance of a comprehensive diagnostic approach as well as continued investigation into CVD pathophysiology using PET-based techniques, which may guide the development of innovative therapeutic strategies.

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.

Introduction Atherosclerosis, the occlusion of arteries due to the accumulation of fatty substances, cholesterol, calcium, and fibrin in the arterial walls, can result in reduced blood flow and a subsequent decrease in oxygen delivery to the organs supplied by the affected artery, including the brain. Positron emission tomography‐computed tomography (PET‐CT) utilizing 18F‐fluorodeoxyglucose (FDG) and 18F‐Sodium Fluoride (NaF) have demonstrated efficacy in the assessment of cerebral glucose metabolism and atherosclerotic calcification, respectively. However, the reported literature has not clearly correlated arterial disease throughout the body with cerebral hypometabolism. Utilizing a novel integration of FDG and NaF PET/CT imaging, our study explores the link between cardiovascular risk factors and regional cerebral metabolism. Methods We compared 79 healthy controls (mean age 44.5 ± 13.8 years, 53.2% males) and 40 individuals (mean age 55.9 ± 11.9 years, 50% males) at increased risk for cardiovascular disease (CVD) as assessed by the systematic coronary risk evaluation (SCORE) tool. All subjects underwent whole‐body FDG‐PET/CT imaging. [18F]fluoride PET/CT imaging was performed using hybrid PET/CT scanners with image correction and reconstruction processes following standard protocols. The quantitative regional analysis of PET images was performed using MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, Ohio). 70 whole brain structures were analyzed in each subject. MIMneuro provided region‐based analysis, with z‐scores generated by comparing the patient to the selected age‐matched set of normal controls. Using OsiriX MD software, [18F]fluoride PET/CT scans were analyzed with regions of interest (ROIs) manually drawn to assess carotid calcification and standardized uptake value mean (SUVmean), along with ROI volume values. Correlations between the degree of molecular calcification and cerebral FDG uptake in patients with cardiovascular risk factors were evaluated using Pearson’s R, with the significance threshold set at P < 0.05. Results Unhealthy patients demonstrated significant negative correlations between increased calcification in the carotid arteries, as assessed by NaF‐PET, and metabolic activity in the anterior cingulate (r = ‐0.42, p = 0.008) and cingulate regions (r = ‐0.34, p = 0.036). Conversely, healthy patients exhibited significant positive correlations in the pons (r = 0.25, p = 0.042) and pontine tegmentum (r = 0.34, p = 0.005), suggestive of a compensatory mechanism to maintain autonomic and motor functions. Conclusion The present study provides insight regarding the interplay between arterial calcification and neural metabolic activity, particularly as it pertains to regions supplied by the anterior cerebral artery. Our investigation suggests that calcification in the carotid arteries, which give rise to the ACA, has a deleterious impact on the function of the cingulate gyrus. Additionally, the observed positive correlation in the pons and pontine tegmentum in healthy individuals raises intriguing questions regarding potential compensatory mechanisms that may help maintain autonomic and motor functions despite vascular impediments. Understanding the temporal progression of vascular calcification allows for the optimization of surgical strategy and timing, potentially reducing stroke risk and improving patient outcomes. These findings underscore the necessity of persistent surveillance and targeted management strategies concerning carotid calcification.

Introduction Cerebrovascular disease (CVD), particularly carotid artery atherosclerosis, contributes substantially to global morbidity and mortality. The ability to precisely detect atherosclerosis is crucial, as it directly influences patient management, including decisions regarding surgical interventions. Given the high prevalence and severe outcomes of CVD, there is an urgent need for improved early detection methods. Utilizing a novel approach, this study pioneers the use of 18F‐sodium fluoride (NaF) PET/CT imaging for the early identification of microcalcification, a key marker of atherosclerosis. A nuanced understanding of vascular calcification's temporal progression may aid in optimally timing surgical interventions, such as carotid endarterectomy or carotid artery stenting, thereby reducing stroke risk. Methods Our study participant is a 31‐year‐old male with atrial fibrillation, multiple cardiovascular risk factors, and class 2 obesity, enrolled in the Cardiovascular Molecular Calcification Assessed by 18F‐NaF PET/CT (CAMONA) study. The patient underwent both FDG‐PET/CT and NaF‐PET/CT imaging. We utilized OsiriX MD software v.13.0.1 (Pixmeo SARL, Bernex, Switzerland), to compute the standardized uptake value (SUVmean), serving as a measure of disease progression in both the global brain and the bilateral carotid arteries. Subsequently, we employed MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, OH, USA) to conduct a comprehensive regional brain metabolism analysis, harnessing the power of an integrated anatomical atlas. Results NaF‐PET/CT imaging revealed elevated NaF uptake in the bilateral carotid arteries (z‐score = 0.012), suggesting notable microcalcification. Conversely, FDG‐PET/CT imaging revealed low FDG uptake in the carotid arteries, with an average SUVmean of 0.66 for both right and left carotids and a z‐score of −2.32. Analysis of global brain metabolism demonstrated decreased FDG uptake detected by FDG‐PET/CT (z‐score = ‐2.32). Concurrently, we identified a decline in regional brain metabolism, with prominent decreases observed in regions including the brainstem (z score = −1.95), medial temporal lobe (z‐score = −1.81), cerebellum (z–score = −2.13), hippocampus (z‐score = −2.13), inferior frontal gyrus (z‐score = −3.53), lateral orbital gyrus (z‐score = −3.24), and putamen (z‐score = −2.47) (Figure 1). Conclusion Our findings highlight the potential of NaF‐PET/CT imaging to enhance early detection of carotid artery atherosclerosis and cerebral hypometabolism. These results highlight the subtle, yet potent, potential of NaF‐PET/CT scans to detect active, asymptomatic cases where FDG‐PET/CT scans may not indicate high activity. The findings suggest that NaF‐PET could play a pivotal role in diagnosing and managing CVD where traditional tracers encounter limitations. Early recognition of these alterations facilitates clinical decision‐making, including determining the necessity and timing of surgical intervention. This advanced diagnostic tool presents an opportunity to improve pre‐operative assessments by providing insights into disease progression prior to macrocalcification development, a clear advantage over existing imaging modalities. The correlation between vascular calcification and decreased cerebral metabolism enhances our understanding of CVD pathophysiology, thereby paving the way for transformative therapeutic interventions. While these findings provide preliminary insight, further research is crucial to corroborate our results and delineate their potentially transformative implications on patient care, particularly in the context of surgical interventions.

Introduction Emerging evidence suggests a robust association between cardiovascular disease (CVD) and cognitive decline, accentuating the necessity for early detection and intervention. 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) has proven efficacious in identifying metabolic neurological changes at a molecular level, even before conventional imaging methods can detect structural changes. This study analyzed regional glucose metabolism in individuals with known CVD risk factors. The detection of such metabolic changes could assist in determining the necessity and timing of vascular interventions, such as carotid endarterectomy (CEA) or carotid artery angioplasty with stenting (CAS), contributing to improved patient outcomes and reduced postoperative complications. Methods We compared 79 healthy controls (mean age 44.5 ± 13.8 years, 53.2% males) and 40 individuals (mean age 55.9 ± 11.9 years, 50% males) at increased risk for cardiovascular disease (CVD) as assessed by the systematic coronary risk evaluation tool. All subjects were grouped into two age‐matched cohorts: younger (

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.

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.

BackgroundPeritoneal metastasis (PM) from colorectal cancer carries a dismal prognosis despite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). With a median time to recurrence of 11–12 months, there is a need for novel therapies. Radspherin® consists of the α-emitting radionuclide radium-224 (224Ra), which has a half-life of 3.6 days and is adsorbed to a suspension of biodegradable calcium carbonate microparticles that are designed to give short-range radiation to the serosal peritoneal surface linings, killing free-floating and/or tumor cell clusters that remain after CRS-HIPEC.MethodsA first-in-human phase 1 study (EudraCT 2018–002803-33) was conducted at two specialized CRS-HIPEC centers. Radspherin® was administered intraperitoneally 2 days after CRS-HIPEC. Dose escalation at increasing activity dose levels of 1-2-4-7-MBq, a split-dose repeated injection, and expansion cohorts were used to evaluate the safety and tolerability of Radspherin®. The aim was to explore the recommended dose and biodistribution using gamma-camera imaging. The results from the planned safety interim analysis after the completion of the dose-limiting toxicity (DLT) period of 30 days are presented.ResultsTwenty-three patients were enrolled: 14 in the dose escalation cohort, three in the repeated cohort, and six in the expansion cohort. Of the 23 enrolled patients, seven were men and 16 were women with a median age of 64 years (28–78). Twelve patients had synchronous PM stage IV and 11 patients had metachronous PM [primary stage II; (6) and stage III; (5)], with a disease-free interval of 15 months (3–30). The peritoneal cancer index was median 7 (3–19), operation time was 395 min (194–515), and hospital stay was 12 days (7–37). A total of 68 grade 2 adverse events were reported for 17 patients during the first 30 days; most were considered related to CRS and/or HIPEC. Only six of the TEAEs were evaluated as related to Radspherin®. One TEAE, anastomotic leakage, was reported as grade 3. Accordion ≥3 grade events occurred in a total of four of the 23 patients: reoperation due to anastomotic leaks (two) and drained abscesses (two). No DLT was documented at the 7 MBq dose level that was then defined as the recommended dose. The biodistribution of Radspherin® showed a relatively even peritoneal distribution.ConclusionAll dose levels of Radspherin® were well tolerated, and DLT was not reached. No deaths occurred, and no serious adverse events were considered related to Radspherin®.Clinical Trial Registration:Clinicaltrials.gov, NCT 03732781.

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.

AimTwo ongoing phase I studies are investigating the use of radium-224 adsorbed to calcium carbonate micro particles (224Ra-CaCO3-MP) to treat peritoneal metastasis originating from colorectal or ovarian cancer. The aim of this work was to study the level of radiation exposure from the patients to workers at the hospital, carers and members of the public.MethodSix patients from the phase 1 trial in patients with colorectal cancer were included in this study. Two days after cytoreductive surgery, they were injected with 7 MBq of 224Ra-CaCO3-MP. At approximately 3, 24 and 120 h after injection, the patients underwent measurements with an ionization chamber and a scintillator-based iodide detector, and whole body gamma camera imaging. The patient was modelled as a planar source to calculate dose rate as a function of distance. Scenarios varying in duration and distance from the patient were created to estimate the potential effective doses from external exposure. Urine and blood samples were collected at approximately 3, 6, 24, 48 and 120 h after injection of 224Ra-CaCO3-MP, to estimate the activity concentration of 224Ra and 212Pb.ResultsThe patients’ median effective whole-body half-life of 224Ra-CaCO3-MP ranged from 2.6 to 3.5 days, with a mean value of 3.0 days. In the scenarios with exposure at the hospital (first 8 days), sporadic patient contact resulted in a range of 3.9–6.8 μSv per patient, and daily contact resulted in 4.3–31.3 μSv depending on the scenario. After discharge from the hospital, at day 8, the highest effective dose was received by those with close daily contact; 18.7–83.0 μSv. The highest activity concentrations of 224Ra and 212Pb in urine and blood were found within 6 h, with maximum values of 70 Bq/g for 224Ra and 628 Bq/g for 212Pb.ConclusionThe number of patients treated with 224Ra-CaCO3-MP that a single hospital worker - involved in extensive care - can receive per year, before effective doses of 6 mSv from external exposure is exceeded, is in the order of 200–400. Members of the public and family members are expected to receive well below 0.25 mSv, and therefore, no restrictions to reduce external exposure should be required.

Metastases are the primary cause of death among cancer patients and efficacious new treatments are sorely needed. Targeted alpha-emitting radiopharmaceuticals that are highly cytotoxic may fulfill this critical need. The focus of this paper is to describe and explore a novel technology that may improve the therapeutic effect of targeted alpha therapy by combining two radionuclides from the same decay chain in the same solution. We hypothesize that the dual targeting solution containing bone-seeking 224Ra and cell-directed complexes of progeny 212Pb is a promising approach to treat metastatic cancers with bone and soft tissue lesions as well as skeletal metastases of mixed lytic/osteoblastic nature. A novel liquid 224Ra/212Pb-generator for rapid preparation of a dual targeting solution is described. Cancer cell targeting monoclonal antibodies, their fragments, synthetic proteins or peptides can all be radiolabeled with 212Pb in the 224Ra-solution in transient equilibrium with daughter nuclides. Thus, 224Ra targets stromal elements in sclerotic bone metastases and 212Pb-chelated-conjugate targets tumor cells of metastatic prostate cancer or osteosarcoma. The dual targeting solution may also be explored to treat metastatic breast cancer or multiple myeloma after manipulation of bone metastases to a more osteoblastic phenotype by the use of bisphosphonates, denosumab, bortezomib or hormone therapy prior to treatment. This may improve targeting of bone-seeking 224Ra and render an augmented radiation dose deposited within metastases. Our preliminary preclinical studies provide conceptual evidence that the dual 224Ra-solution with bone or tumor-targeted delivery of 212Pb has potential to inhibit cancer metastases without significant toxicity. In some settings, the use of a booster dose of purified 212Pb-conjugate alone could be required to elevate the effect of this tumor cell directed component, if needed, e.g., in a fractionated treatment regimen, where the dual targeting solution will act as maintenance treatment.

Recent advances in the treatment of multiple myeloma (MM) have increased the need for accurate diagnosis and detection of minimal residual disease (MRD), disease characterization and localization, and response evaluation and prognostication. Positron emission tomography (PET)/computed tomography (CT) imaging combines molecular and morphological information and has been shown to be especially valuable in this disease. The most frequently used PET tracer in MM is the glucose analog 18F-fluorodeoxyglucose ([18F]FDG). [18F]FDG PET/CT has a sensitivity for detection of MM between 80% to 100% and is currently the main imaging modality for assessing treatment response and for determining MRD. However, 18F-FDG PET/CT has some limitations, and imaging with alternative tracers that may overcome these constraints should be further explored. This article discusses new targets for PET/CT imaging in the assessment of MM.

Osteosarcoma patients with overt metastases at primary diagnosis have a 5-year survival rate of less than 20%. TP-3 is a murine IgG2b monoclonal antibody with high affinity for an epitope residing on the p80 osteosarcoma cell surface membrane antigen. The tumor-associated antigen p80 is overexpressed in osteosarcomas, and has very low normal tissue expression. We propose a novel dual alpha targeting solution containing two radionuclides from the same decay chain, including the bone-seeking 224Ra, and cancer cell-surface seeking 212Pb-TCMC-TP-3 for the treatment of osteoblastic bone cancers, circulating cancer cells and micrometastases. In this in vitro study, the cytotoxic effects of 212Pb-TCMC-TP-3 (single alpha solution) and 224Ra/212Pb-TCMC-TP-3 (dual alpha solution) were investigated in a multicellular spheroid model mimicking micrometastatic disease in osteosarcoma. OHS spheroids with diameters of 253 ± 98 μm treated with 4.5, 2.7, and 3.3 kBq/ml of 212Pb-TCMC-TP-3 for 1, 4, and 24 h, respectively, were disintegrated within 3 weeks. The 212Pb-TCMC-TP-3 induced a 7-fold delay in spheroid doubling time compared to a 28-times higher dose with the non-specific 212Pb-TCMC-rituximab. The 224Ra/212Pb-TCMC-TP-3 completely disintegrated spheroids with diameters of 218–476 μm within 3 and 2 weeks after 4 and 24 h incubation with 5 kBq/ml, respectively. Treatment with 1 kBq/ml of 224Ra/212Pb-TCMC-TP-3 for 24 h caused an 11.4-fold reduction in spheroid viability compared with unconjugated 224Ra/212Pb. The single and dual alpha solutions with TP-3 showed cytotoxicity in spheroids of clinically relevant size, which warrant further testing of the dual alpha solution using in vivo osteosarcoma models.

BackgroundAdoptive cellular therapy (ACT) with genetically modified T cells aims to redirect T cells against resistant cancers through introduction of a T cell receptor (TCR). The Radium-4 TCR was isolated from a responding patient in a cancer vaccination study and recognizes the enzymatic component of human Telomerase Reverse Transcriptase (hTERT) presented on MHC class II (HLA-DP04). hTERT is a constitutively overexpressed tumor-associated antigen present in most human cancers, including non-small-cell lung cancer (NSCLC), which is the second most common type of cancer worldwide. Treatment alternatives for relapsing NSCLC are limited and survival is poor. To improve patient outcome we designed a TCR-based ACT study targeting hTERT.MethodsT-RAD is a phase I/II study to evaluate the safety and efficacy of Radium-4 mRNA electroporated autologous T cells in the treatment of metastatic NSCLC with no other treatment option. Transient TCR expression is applied for safety considerations. Participants receive two intravenous injections with escalating doses of redirected T cells weekly for 6 consecutive weeks. Primary objectives are safety and tolerability. Secondary objectives include progression-free survival, time to progression, overall survival, patient reported outcomes and overall radiological response.DiscussionTreatment for metastatic NSCLC is scarce and new personalized treatment options are in high demand. hTERT is a tumor target applicable to numerous cancer types. This proof-of-concept study will explore for the first time the safety and efficacy of TCR mRNA electroporated autologous T cells targeting hTERT. The T-RAD study will thus evaluate an attractive candidate for future immunotherapy of solid tumors.

For more than two years, lingering sequalae of COVID-19 have been extensively investigated. Approximately 10% of individuals infected by COVID-19 have been found to experience long-term symptoms termed “long COVID-19”. The neurological and psychiatric manifestations of long COVID-19 are of particular concern. While pathogenesis remains unclear, emerging imaging studies have begun to better elucidate certain pathological manifestation. Of specific interest is imaging with [18F]FDG PET which directly reflects cellular glycolysis often linked to metabolic and inflammatory processes. Seeking to understand the molecular basis of neurological features of long COVID-19, this review encompasses the most recent [18F]FDG PET literature in this area.

In June 2021, the US Federal Drug and Food Administration (FDA) granted accelerated approval for the antibody aducanumab and, in January 2023, also for the antibody lecanemab, based on a perceived drug-induced removal of cerebral amyloid-beta as assessed by amyloid-PET and, in the case of lecanemab, also a presumption of limited clinical efficacy. Approval of the antibody donanemab is awaiting further data. However, published trial data indicate few, small and uncertain clinical benefits, below what is considered “clinically meaningful” and similar to the effect of conventional medication. Furthermore, a therapy-related decrease in the amyloid-PET signal may also reflect increased cell damage rather than simply “amyloid removal”. This interpretation is more consistent with increased rates of amyloid-related imaging abnormalities and brain volume loss in treated patients, relative to placebo. We also challenge the current diagnostic criteria for AD based on amyloid-PET imaging biomarkers and recommend that future anti-AD therapy trials apply: (1) diagnosis of AD based on the co-occurrence of cognitive decline and decreased cerebral metabolism assessed by FDA-approved FDG-PET, (2) therapy efficacy determined by favorable effect on cognitive ability, cerebral metabolism by FDG-PET, and brain volumes by MRI, and (3) neuropathologic examination of all deaths occurring in these trials.

Rheumatoid arthritis (RA) involves chronic inflammation of synovial joints, causing pain, stiffness, and limited mobility. 18F-sodium fluoride (NaF) is a PET tracer whose uptake reflects bone turnover, while 18F-fludeoxyglucose (FDG) shows glucose metabolism and can serve as a marker for inflammation. The aim of this study is to determine the feasibility of calculating the FDG and NaF mean standardized uptake value (SUVmean) in the knee joint, hip joint, and sacroiliac (SI) joint of RA patients and to determine their association with patient characteristics. Prospective FDG-PET/CT as well as NaF-PET/CT imaging was performed on 18 RA patients. The global SUVmean was calculated on FDG-PET/CT and NaF-PET/CT images using a semiautomated CT-based method of segmentation. FDG and NaF uptake were found to be significantly correlated in the knee (r = 0.77, p < 0.001), but not in the hip and SI joints. In the knee, both NaF SUVmean and FDG SUVmean were significantly correlated with body weight, BMI, leptin, and sclerostin levels (p < 0.05). NaF SUVmean was significantly positively correlated with BMI and leptin for both the hip and SI joints (p < 0.05). No significant correlation was observed between either PET parameter and age, height, erythrocyte sedimentation rate (ESR), and interleukins 1 and 6 (IL-1 and IL-6); however, FDG was correlated with inflammatory markers such as C-reactive protein (CRP) and patient global visual analogue scale (VAS-PtGlobal) in some joints. In this study, both FDG and NaF uptake were quantified in large joints of patients with RA using CT segmentation. NaF and FDG SUVmean were correlated with clinical variables related to body weight and adiposity, suggesting that degenerative joint disease may play a larger role in influencing the uptake of these tracers in large joints than RA disease activity. FDG and its correlation with markers of inflammation such as CRP and VAS-PtGlobal suggests that this tracer may serve as a more specific marker for RA disease activity than NaF. Larger prospective and longitudinal data are necessary to gain a better understanding of the roles of FDG and NaF in evaluating RA joint activity in these joints.

Abstract Castleman disease (CD) describes a group of rare hematologic conditions involving lymphadenopathy with characteristic histopathology and a spectrum of clinical abnormalities. CD is divided into localized or unicentric CD (UCD) and multicentric CD (MCD) by imaging. MCD is further divided based on etiological driver into human herpesvirus-8-associated MCD, POEMS-associated MCD, and idiopathic MCD. There is notable heterogeneity across MCD, but increased level of pro-inflammatory cytokines, particularly interleukin-6, is an established disease driver in a portion of patients. FDG-PET/CT can help determine UCD versus MCD, evaluate for neoplastic conditions that can mimic MCD clinico-pathologically, and monitor therapy responses. CD requires more robust characterization, earlier diagnosis, and an accurate tool for both monitoring and treatment response evaluation; FDG-PET/CT is particularly suited for this. Moving forward, future prospective studies should further characterize the use of FDG-PET/CT in CD and specifically explore the utility of global disease assessment and dual time point imaging. Trial registration ClinicalTrials.gov, NCT02817997, Registered 29 June 2016, https://clinicaltrials.gov/ct2/show/NCT02817997

The application of [18F]-fluorodeoxyglucose ([18F]FDG) as a radiotracer to detect sites of inflammation (either due to bacterial infection or primary inflammation) has led to exploring the role of PET in visualizing bacteria directly at sites of infection. However, the results from such efforts are controversial and inconclusive so far. We aimed to assess the limitations of PET as an effective modality in the diagnosis of bacterial infections. Inflammation due to bacterial infections can be visualized by using [18F]FDG-PET. However, the non-specificity of [18F]FDG makes it undesirable to visualize bacteria as the underlying cause of inflammation. Hence, more specific radiotracers that possibly bind to or accumulate in bacteria-specific receptors or enzymes are being explored. Several radiotracers, including 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS), 6-[18F]-fluoromaltose, [11C]para-aminobenzoic acid ([11C]PABA), radiolabeled trimethoprim (11C-TMP) and its analog fluoropropyl-trimethoprim (18F-FPTMP), other radiolabeled sugars, and antimicrobial drugs have been used to image microorganisms. Unfortunately, no progress has been made in translating the results to routine human use; feasibility and other factors have constrained their success in clinical settings. In the current article, we discuss the limitations of direct bacterial visualization with PET tracers, but emphasize the important role of [18F]FDG-PET as the only option for detecting evidence of infection.

Abstract Background 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is used in the clinical management of oncologic and inflammatory pathologies. It may have utility in detecting radiotherapy (RT)-induced damage of oral tissues. Thus, the aim of the present study was to use FDG-PET/CT to evaluate parotid gland inflammation following RT in patients with head and neck cancer (HNC). Methods This retrospective study included patients with HNC treated with photon, proton, or combined photon/proton RT, in addition to chemotherapy. All patients received FDG-PET/CT imaging pre-treatment and 3 months post-treatment. The average mean standardized uptake value (Avg SUVmean) and the average maximum standardized uptake value (Avg SUVmax) of the left and right parotid glands were determined by global assessment of FDG activity using OsiriX MD software. A two-tailed paired t test was used to compare Avg SUVmean and Avg SUVmax pre- and post-RT. Results Forty-seven HNC patients were included in the study. Parotid gland Avg SUVmean was significantly higher at 3 months post-treatment than pre-treatment (p < 0.05) in patients treated with photon RT, but no significant differences were found between pre- and post-treatment Avg SUVmean in patients treated with proton RT or combined photon/proton RT. Conclusion Our results suggest that photon RT may cause radiation-induced inflammation of the parotid gland, and that proton RT, which distributes less off-target radiation, is a safer treatment alternative.

The method of 18F-sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) of atherosclerosis was introduced 12 years ago. This approach is particularly interesting because it demonstrates microcalcification as an incipient sign of atherosclerosis before the development of arterial wall macrocalcification detectable by CT. However, this method has not yet found its place in the clinical routine. The more exact association between NaF uptake and future arterial calcification is not fully understood, and it remains unclear to what extent NaF-PET may replace or significantly improve clinical cardiovascular risk scoring. The first 10 years of publications in the field were characterized by heterogeneity at multiple levels, and it is not clear how the method may contribute to triage and management of patients with atherosclerosis, including monitoring effects of anti-atherosclerosis intervention. The present review summarizes findings from the recent 2¾ years including the ability of NaF-PET imaging to assess disease progress and evaluate response to treatment. Despite valuable new information, pertinent questions remain unanswered, not least due to a pronounced lack of standardization within the field and of well-designed long-term studies illuminating the natural history of atherosclerosis and effects of intervention.

Arteriosclerosis and its sequelae are the most common cause of death in diabetic patients and one of the reasons why diabetes has entered the top 10 causes of death worldwide, fatalities having doubled since 2000. The literature in the field claims almost unanimously that arteriosclerosis is more frequent or develops more rapidly in diabetic than non-diabetic subjects, and that the disease is caused by arterial inflammation, the control of which should therefore be the goal of therapeutic efforts. These views are mostly based on indirect methodologies, including studies of artery wall thickness or stiffness, or on conventional CT-based imaging used to demonstrate tissue changes occurring late in the disease process. In contrast, imaging with positron emission tomography and computed tomography (PET/CT) applying the tracers 18F-fluorodeoxyglucose (FDG) or 18F-sodium fluoride (NaF) mirrors arterial wall inflammation and microcalcification, respectively, early in the course of the disease, potentially enabling in vivo insight into molecular processes. The present review provides an overview of the literature from the more than 20 and 10 years, respectively, that these two tracers have been used for the study of atherosclerosis, with emphasis on what new information they have provided in relation to diabetes and which questions remain insufficiently elucidated.

Common variable immunodeficiency (CVID) is characterized not only by recurrent bacterial infections, but also autoimmune and inflammatory complications including interstitial lung disease (ILD), referred to as granulomatous-lymphocytic interstitial lung disease (GLILD). Some patients with GLILD have waxing and waning radiologic findings, but preserved pulmonary function, while others progress to end-stage respiratory failure. We reviewed 32 patients with radiological features of GLILD from our Norwegian cohort of CVID patients, including four patients with possible monogenic defects. Nineteen had deteriorating lung function over time, and 13 had stable lung function, as determined by pulmonary function testing of forced vital capacity (FVC), and diffusion capacity of carbon monoxide (DLCO). The overall co-existence of other non-infectious complications was high in our cohort, but the prevalence of these was similar in the two groups. Laboratory findings such as immunoglobulin levels and T- and B-cell subpopulations were also similar in the progressive and stable GLILD patients. Thoracic computer tomography (CT) scans were systematically evaluated and scored for radiologic features of GLILD in all pulmonary segments. Pathologic features were seen in all pulmonary segments, with traction bronchiectasis as the most prominent finding. Patients with progressive disease had significantly higher overall score of pathologic features compared to patients with stable disease, most notably traction bronchiectasis and interlobular septal thickening. 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/CT (PET/CT) was performed in 17 (11 with progressive and six with stable clinical disease) of the 32 patients and analyzed by quantitative evaluation. Patients with progressive disease had significantly higher mean standardized uptake value (SUVmean), metabolic lung volume (MLV) and total lung glycolysis (TLG) as compared to patients with stable disease. Nine patients had received treatment with rituximab for GLILD. There was significant improvement in pathologic features on CT-scans after treatment while there was a variable effect on FVC and DLCO.ConclusionPatients with progressive GLILD as defined by deteriorating pulmonary function had significantly greater pathology on pulmonary CT and FDG-PET CT scans as compared to patients with stable disease, with traction bronchiectasis and interlobular septal thickening as prominent features.

Molecular imaging has emerged in the past few decades as a novel means to investigate atherosclerosis. From a pathophysiological perspective, atherosclerosis is characterized by microscopic inflammation and microcalcification that precede the characteristic plaque buildup in arterial walls detected by traditional assessment methods, including anatomic imaging modalities. These processes of inflammation and microcalcification are, therefore, prime targets for molecular detection of atherosclerotic disease burden. Imaging with positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) can non-invasively assess arterial inflammation and microcalcification, respectively. FDG uptake reflects glucose metabolism, which is particularly increased in atherosclerotic plaques retaining macrophages and undergoing hypoxic stress. By contrast, NaF uptake reflects the exchange of hydroxyl groups of hydroxyapatite crystals for fluoride producing fluorapatite, a key biochemical step in calcification of atherosclerotic plaque. Here we review the existing literature on FDG and NaF imaging and their respective values in investigating the progression of atherosclerotic disease. Based on the large volume of data that have been introduced to the literature and discussed in this review, it is clear that PET imaging will have a major role to play in assessing atherosclerosis in the major and coronary arteries. However, it is difficult to draw definitive conclusions on the potential role of FDG in investigating atherosclerosis given the vast number of studies with different designs, image acquisition methods, analyses, and interpretations. Our experience in this domain of research has suggested that NaF may be the tool of choice over FDG in assessing atherosclerosis, especially in the setting of coronary artery disease (CAD). Specifically, global NaF assessment appears to be superior in detecting plaques in tissues with high background FDG activity, such as the coronary arteries.

Somatostatin receptor (SSTR) agonist tracers used in nuclear medicine scans are classically used for neuroendocrine tumor diagnosis and staging. SSTR are however, expressed more widely in a variety of cells as seen in the distribution of physiological tracer uptake during whole body scans. This provides opportunities for using these tracers for applications other than NETs and meningiomas. In this qualitative systematic review, novel diagnostics in SSTR-PET imaging are reviewed. A total of 70 studies comprised of 543 patients were qualitatively reviewed. Sarcoidosis, atherosclerosis and phosphaturic mesenchymal tumors represent the most studied applications currently with promising results. Other applications remain in progress where there are many case reports but a relative dearth of cohort studies. [18F]FDG PET provides the main comparative method in many cases but represents a well-established general PET technique that may be difficult to replace, without prospective clinical studies.

Background and purpose: Multimodal imaging is increasingly included in the assessment of prostate cancer patients, and there is a need to study whether different techniques provide similar or complementary information. In the initial perfusion phase contrast agents and radioactive labelled tracers act as blood-pool agents and may show similar characteristics. The purpose of the current work was to compare time-activity- and time-concentration-curves (TCs) of dynamic 18F-fluciclovine (18F-anti-1-amino-2-[F]-fluorocyclobutane-1-carboxylic acid, FACBC) positron emission tomography (PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). Materials and methods: Dynamic FACBC PET and DCE MRI were performed on 22 patients with intermediate or high-risk prostate cancer within 23 days prior to robot-assisted laparoscopic prostatectomy. Index tumour was delineated in the images using whole mount tissue sections as reference standard. Tumour TCs from PET and MRI were compared visually and quantitatively by calculating correlation coefficients between the curves at different time points after injection. Results: For the first minute post injection, the mean correlation coefficient between the TCs from PET and MRI was 0.92 (range; 0.75–0.99). After the first minute, MRI showed washout while PET showed plateau kinetics. Conclusion: Dynamic FACBC and DCE MRI showed similar wash-in time curve characteristics. At later time points, FACBC plateaued whereas MR contrast medium washed out. In DCE MRI, the usefulness of wash-in information is well documented. Whether wash-in information from dynamic FACBC can provide added value remains to be documented. Keywords: Prostate carcinoma, Fluciclovine, FACBC, MRI, Uptake characteristics

Positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose (FDG) represents a method of detecting and characterizing arterial wall inflammation, with potential applications in the early assessment of vascular disorders such as atherosclerosis. By portraying early-stage molecular changes, FDG-PET findings have previously been shown to correlate with atherosclerosis progression. In addition, recent studies have suggested that microcalcification revealed by 18F-sodium fluoride (NaF) may be more sensitive at detecting atherogenic changes compared to FDG-PET. In this review, we summarize the roles of FDG and NaF in the assessment of atherosclerosis and discuss the role of global assessment in quantification of the vascular disease burden. Furthermore, we will review the emerging applications of FDG-PET in various vascular disorders, including pulmonary embolism, as well as inflammatory and infectious vascular diseases.

There is a well-known association in male patients between mediastinal germ cell tumors (GCT) and hematologic malignancies, with a propensity towards acute megakaryoblastic leukemia. These rare malignancies have been shown to share a common clonal origin, often deduced from the finding of isochromosome 12p, i(12p), in cells from both the solid tumor and the leukemia, and thus are now known to represent different manifestations of the same clonal process. We treated a young female patient with a malignant phyllodes tumor followed by an acute megakaryoblastic leukemia and found several of the same marker chromosomes by karyotype analysis of cells from both the tumor and the leukemia implying a common clonal origin of the two. To the best of our knowledge, this has not been demonstrated in phyllodes tumors before, but indicates that the same type of leukemization may occur of this tumor as has been described in mediastinal GCT.