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Diabetes Care Nov 2023Experimental evidence suggests that metabolic syndrome (MetS) is associated with changes in cardiac metabolism. Whether this association occurs in humans is unknown.
OBJECTIVE
Experimental evidence suggests that metabolic syndrome (MetS) is associated with changes in cardiac metabolism. Whether this association occurs in humans is unknown.
RESEARCH DESIGN AND METHODS
821 asymptomatic individuals from the Progression of Early Subclinical Atherosclerosis (PESA) study (50.6 [46.9-53.6] years, 83.7% male) underwent two whole-body 18F-fluorodeoxyglucose positron emission tomography-magnetic resonance (18F-FDG PET-MR) 4.8 ± 0.6 years apart. Presence of myocardial 18F-FDG uptake was evaluated qualitatively and quantitatively. No myocardial uptake was grade 0, while positive uptake was classified in grades 1-3 according to target-to-background ratio tertiles.
RESULTS
One hundred fifty-six participants (19.0%) showed no myocardial 18F-FDG uptake, and this was significantly associated with higher prevalence of MetS (29.0% vs. 13.9%, P < 0.001), hypertension (29.0% vs. 18.0%, P = 0.002), and diabetes (11.0% vs. 3.2%, P < 0.001), and with higher insulin resistance index (HOMA-IR, 1.64% vs. 1.23%, P < 0.001). Absence of myocardial uptake was associated with higher prevalence of early atherosclerosis (i.e., arterial 18F-FDG uptake, P = 0.004). On follow-up, the associations between myocardial 18F-FDG uptake and risk factors were replicated, and MetS was more frequent in the group without myocardial uptake. The increase in HOMA-IR was associated with a progressive decrease in myocardial uptake (P < 0.001). In 82% of subjects, the categorization according to presence/absence of myocardial 18F-FDG uptake did not change between baseline and follow-up. MetS regression on follow-up was associated with a significant (P < 0.001) increase in myocardial uptake.
CONCLUSIONS
Apparently healthy individuals without cardiac 18F-FDG uptake have higher HOMA-IR and higher prevalence of MetS traits, cardiovascular risk factors, and early atherosclerosis. An improvement in cardiometabolic profile is associated with the recovery of myocardial 18F-FDG uptake at follow-up.
Topics: Male; Humans; Female; Fluorodeoxyglucose F18; Metabolic Syndrome; Insulin Resistance; Heart; Atherosclerosis; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 37713581
DOI: 10.2337/dc23-0871 -
Alzheimer's Research & Therapy Aug 2023Despite the high sensitivity of cerebrospinal fluid (CSF) amyloid beta (Aβ) to detect amyloid pathology, the Aβ/Aβ ratio (amyR) better estimates amyloid load, with...
Different associations between amyloid-βeta 42, amyloid-βeta 40, and amyloid-βeta 42/40 with soluble phosphorylated-tau and disease burden in Alzheimer's disease: a cerebrospinal fluid and fluorodeoxyglucose-positron emission tomography study.
BACKGROUND
Despite the high sensitivity of cerebrospinal fluid (CSF) amyloid beta (Aβ) to detect amyloid pathology, the Aβ/Aβ ratio (amyR) better estimates amyloid load, with higher specificity for Alzheimer's disease (AD). However, whether Aβ and amyR have different meanings and whether Aβ represents more than an Aβ-corrective factor remain to be clarified. Our study aimed to compare the ability of Aβ and amyR to detect AD pathology in terms of p-tau/Aβ ratio and brain glucose metabolic patterns using fluorodeoxyglucose-positron emission tomography (FDG-PET).
METHODS
CSF biomarkers were analyzed with EUROIMMUN ELISA. We included 163 patients showing pathological CSF Aβ and normal p-tau (A + T - = 98) or pathological p-tau levels (A + T + = 65) and 36 control subjects (A - T -). A + T - patients were further stratified into those with normal (CSFAβ + /amyR - = 46) and pathological amyR (CSFAβ + /amyR + = 52). We used two distinct cut-offs to determine pathological values of p-tau/Aβ: (1) ≥ 0.086 and (2) ≥ 0.122. FDG-PET patterns were evaluated in a subsample of patients (n = 46) and compared to 24 controls.
RESULTS
CSF Aβ levels were the lowest in A - T - and in CSFAβ + /amyR - , higher in CSFAβ + /amyR + and highest in A + T + (F = 50.75; p < 0.001), resembling CSF levels of p-tau (F = 192; p < 0.001). We found a positive association between Aβ and p-tau in A - T - (β = 0.58; p < 0.001), CSFAβ + /amyR - (β = 0.47; p < 0.001), and CSFAβ + /amyR + patients (β = 0.48; p < 0.001) but not in A + T + . Investigating biomarker changes as a function of amyR, we observed a weak variation in CSF p-tau (+ 2 z-scores) and Aβ (+ 0.8 z-scores) in the normal amyR range, becoming steeper over the pathological threshold of amyR (p-tau: + 5 z-scores, Aβ: + 4.5 z-score). CSFAβ + /amyR + patients showed a significantly higher probability of having pathological p-tau/Aβ than CSFAβ + /amyR - (cut-off ≥ 0.086: OR 23.3; cut-off ≥ 0.122: OR 8.8), which however still showed pathological values of p-tau/Aβ in some cases (cut-off ≥ 0.086: 35.7%; cut-off ≥ 0.122: 17.3%) unlike A - T - . Accordingly, we found reduced FDG metabolism in the temporoparietal regions of CSFAβ + /amyR - compared to controls, and further reduction in frontal areas in CSFAβ + /amyR + , like in A + T + .
CONCLUSIONS
Pathological p-tau/Aβ and FDG hypometabolism typical of AD can be found in patients with decreased CSF Aβ levels alone. AmyR positivity, associated with higher Aβ levels, is accompanied by higher CSF p-tau and widespread FDG hypometabolism.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Fluorodeoxyglucose F18; Amyloidogenic Proteins; Cost of Illness
PubMed: 37649105
DOI: 10.1186/s13195-023-01291-w -
Journal of Nuclear Medicine : Official... Aug 2023Radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and Arg-Gly-Asp (RGD) peptides have been extensively investigated for imaging of FAP- and integrin...
Radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and Arg-Gly-Asp (RGD) peptides have been extensively investigated for imaging of FAP- and integrin αβ-positive tumors. In this study, a FAPI-RGD heterodimer was radiolabeled with Ga and evaluated in patients with cancer. We hypothesized that the heterodimer, recognizing both FAP and integrin αβ, would be advantageous because of its dual-receptor-targeting property. The effective dose of Ga-FAPI-RGD was evaluated in 3 healthy volunteers. The clinical feasibility of Ga-FAPI-RGD PET/CT was evaluated in 22 patients with various types of cancer, and the results were compared with those of F-FDG and Ga-FAPI-46. Ga-FAPI-RGD was tolerated well, with no adverse events in any of the healthy volunteers or patients. The effective dose from Ga-FAPI-RGD PET/CT was 1.01 × 10 mSv/MBq. In clinical investigations with different types of cancer, the radiotracer uptake and tumor-to-background ratio (TBR) of primary and metastatic lesions in Ga-FAPI-RGD PET/CT were significantly higher than those in F-FDG PET/CT (primary tumors: SUV, 18.0 vs. 9.1 [ < 0.001], and TBR, 15.2 vs. 5.5 [ < 0.001]; lymph node metastases: SUV, 12.1 vs. 6.1 [ < 0.001], and TBR, 13.3 vs. 4.1 [ < 0.001]), resulting in an improved lesion detection rate and tumor delineation, particularly for the diagnosis of lymph node (99% vs. 91%) and bone (100% vs. 80%) metastases. Ga-FAPI-RGD PET/CT also yielded a higher radiotracer uptake and TBR than Ga-FAPI-46 PET/CT did. Ga-FAPI-RGD exhibited improved tumor uptake and TBR compared with F-FDG and Ga-FAPI PET/CT. This study demonstrated the safety and clinical feasibility of Ga-FAPI-RGD PET/CT for imaging of various types of cancer.
Topics: Humans; Integrin alphaVbeta3; Gallium Radioisotopes; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Oligopeptides; Positron-Emission Tomography; Lymphatic Metastasis; Fibroblasts; Quinolines
PubMed: 37142301
DOI: 10.2967/jnumed.122.265383 -
Cells Aug 2023Atherosclerosis is a chronic systemic inflammatory condition of the vasculature and a leading cause of stroke. Luminal stenosis severity is an important factor in... (Review)
Review
Atherosclerosis is a chronic systemic inflammatory condition of the vasculature and a leading cause of stroke. Luminal stenosis severity is an important factor in determining vascular risk. Conventional imaging modalities, such as angiography or duplex ultrasonography, are used to quantify stenosis severity and inform clinical care but provide limited information on plaque biology. Inflammatory processes are central to atherosclerotic plaque progression and destabilization. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a validated technique for quantifying plaque inflammation. In this review, we discuss the evolution of FDG-PET as an imaging modality to quantify plaque vulnerability, challenges in standardization of image acquisition and analysis, its potential application to routine clinical care after stroke, and the possible role it will play in future drug discovery.
Topics: Animals; Plaque, Atherosclerotic; Constriction, Pathologic; Fluorodeoxyglucose F18; Positron-Emission Tomography; Stroke; Coleoptera; Inflammation; Plaque, Amyloid
PubMed: 37626883
DOI: 10.3390/cells12162073 -
European Radiology Nov 2023
Topics: Humans; Gallium Radioisotopes; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18
PubMed: 37171487
DOI: 10.1007/s00330-023-09715-9 -
Clinical Nuclear Medicine Sep 202368Ga-DOTA-FAPI-04 PET/CT was performed on a cohort of 21 patients with known SAPHO syndrome. All patients underwent 68Ga-DOTA-FAPI-04 and 18F-FDG PET/CT on 2 consecutive...
PATIENTS AND METHODS
68Ga-DOTA-FAPI-04 PET/CT was performed on a cohort of 21 patients with known SAPHO syndrome. All patients underwent 68Ga-DOTA-FAPI-04 and 18F-FDG PET/CT on 2 consecutive days. The positive rates of the PET/CT scans at the sites of the osteoarticular symptom, the uptake values, and agreement with clinical osteoarticular symptom were compared.
RESULTS
A total of 38 sites of involvement were detected. 18F-FDG PET/CT revealed 28 lesions. In contrast, 68Ga-DOTA-FAPI-04 PET/CT detected not only all lesions shown on 18F-FDG PET/CT but additional 10 lesions. 68Ga-DOTA-FAPI-04 scan also demonstrated significantly higher uptake and target-to-background ratio than 18F-FDG studies in the skeletal involvements. The agreement between 68Ga-DOTA-FAPI-04-positive lesions and current osteoarticular lesions was substantial (κ = 0.79, P < 0.001), whereas 18F-FDG had low to moderate agreement with clinical symptoms (κ = 0.52, P < 0.001).
CONCLUSIONS
68Ga-DOTA-FAPI-04 has potential as a promising imaging agent for the evaluation of SAPHO syndrome.
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Acquired Hyperostosis Syndrome; Gallium Radioisotopes
PubMed: 37543757
DOI: 10.1097/RLU.0000000000004724 -
EMBO Molecular Medicine Jan 2024Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition associated with Marfan syndrome (MFS), a disease caused by fibrillin-1 gene mutations....
Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition associated with Marfan syndrome (MFS), a disease caused by fibrillin-1 gene mutations. While various conditions causing TAAD exhibit aortic accumulation of the proteoglycans versican (Vcan) and aggrecan (Acan), it is unclear whether these ECM proteins are involved in aortic disease. Here, we find that Vcan, but not Acan, accumulated in Fbn1 aortas, a mouse model of MFS. Vcan haploinsufficiency protected MFS mice against aortic dilation, and its silencing reverted aortic disease by reducing Nos2 protein expression. Our results suggest that Acan is not an essential contributor to MFS aortopathy. We further demonstrate that Vcan triggers Akt activation and that pharmacological Akt pathway inhibition rapidly regresses aortic dilation and Nos2 expression in MFS mice. Analysis of aortic tissue from MFS human patients revealed accumulation of VCAN and elevated pAKT-S473 staining. Together, these findings reveal that Vcan plays a causative role in MFS aortic disease in vivo by inducing Nos2 via Akt activation and identify Akt signaling pathway components as candidate therapeutic targets.
Topics: Animals; Humans; Mice; Aortic Aneurysm, Thoracic; Aortic Diseases; Aortic Dissection; Azides; Deoxyglucose; Marfan Syndrome; Nitric Oxide Synthase Type II; Proto-Oncogene Proteins c-akt; Versicans
PubMed: 38177536
DOI: 10.1038/s44321-023-00009-7 -
Neuroradiology Aug 2023Anti-leucine glioma-inactivated protein 1 (anti-LGI1) autoimmune encephalitis (AE) presents as subacute memory loss, behavioral changes, and seizures. Diagnosis and...
OBJECTIVES
Anti-leucine glioma-inactivated protein 1 (anti-LGI1) autoimmune encephalitis (AE) presents as subacute memory loss, behavioral changes, and seizures. Diagnosis and treatment delays can result in long term sequelae, including cognitive impairment. F-FDG PET/CT may be more sensitive than MRI in patients with AE. Our objective was to determine if anti-LGI1 is associated with a distinct pattern of FDG uptake and whether this pattern persists following treatment.
METHODS
NineteenF-FDG PET/CT brain scans (13 pre-treatment, 6 convalescent phase) for 13 patients with anti-LGI1 were studied using NeuroQ™ and CortexID™. The sensitivity of the PET images was compared to MRI. The Z scores of 47 brain regions between the pre-treatment and next available follow-up images during convalescence were compared.
RESULTS
All F-FDG PET/CT scans demonstrated abnormal FDG uptake, while only 6 (42.9%) pre-treatment brain MRIs were abnormal. The pre-treatment scans demonstrated hypermetabolism in the bilateral medial temporal cortices, basal ganglia, brain stem, and cerebellum and hypometabolism in bilateral medial and mid frontal, cingulate, and parietotemporal cortices. Overall, the brain uptake during convalescence showed improvement of the Z scores towards 0 or normalization of previous hypometabolic activity in medial frontal cortex, inferior frontal cortex, Broca's region, parietotemporal cortex, and posterior cingulate cortex and previous hypermetabolic activity in medial temporal cortices, caudate, midbrain, pons and cerebellum.
CONCLUSIONS
Brain FDG uptake was more commonly abnormal than MRI in the pre-treatment phase of anti-LGI1, and patterns of dysmetabolism differed in the pre-treatment and convalescent phases. These findings may expedite the diagnosis, treatment, and monitoring of anti-LGI1 patients.
Topics: Humans; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Leucine; Convalescence; Magnetic Resonance Imaging; Glioma; Autoimmune Diseases of the Nervous System
PubMed: 37264220
DOI: 10.1007/s00234-023-03165-2 -
European Journal of Nuclear Medicine... Sep 2023The purpose of this study is to compare the ability of [Ga]Ga-DOTA-FAPI-04 PET/CT and [F]FDG PET/CT to stratify the malignancy and invasiveness of thymic epithelial...
PURPOSE
The purpose of this study is to compare the ability of [Ga]Ga-DOTA-FAPI-04 PET/CT and [F]FDG PET/CT to stratify the malignancy and invasiveness of thymic epithelial tumours (TETs).
METHODS
From April 2021 to November 2022, participants with suspected TETs confirmed by histopathology or follow-up imaging were prospectively analysed. All participants underwent [F]FDG and [Ga]Ga-DOTA-FAPI-04 PET/CT within 1 week. Clinical characteristics, CT features, and metabolic parameters (maximum standardized uptake value [SUV] and tumour-to-mediastinum ratio [TMR]) of subjects with different pathological types and stages were compared. The diagnostic capacities of [F]FDG and [Ga]Ga-DOTA-FAPI-04 PET/CT were compared using receiver operating characteristic (ROC) curves and McNemar's test.
RESULTS
Fifty-seven participants were included. [Ga]Ga-DOTA-FAPI-04 PET/CT was superior to [F]FDG PET/CT in differentiating thymomas from thymic carcinomas (TCs) (AUC: 0.99 vs. 0.90, P = 0.02). Logistic regression revealed that SUV (P = 0.04) was a significant predictive factor for TCs. SUV and TMR showed an excellent ability to differentiate low-risk thymomas (types A, AB, and B1), high-risk thymomas (types B2 and B3), and TCs (both P < 0.001). In thymomas, only SUV (P < 0.001), TMR (P < 0.001), and nonsmooth edges (P = 0.02) were significantly higher in the advanced-stage (Masaoka-Koga [MK] stage III/IV) group than in the early-stage group (MK stage I/II). Compared with [F]FDG PET/CT, [Ga]Ga-DOTA-FAPI-04 PET/CT showed significantly higher specificity (67% [46 of 69] vs. 93% [64 of 69], P < 0.001) in the detection of lymph node metastases and higher sensitivity (49% [19 of 39] vs. 97% [38 of 39], P < 0.001) in evaluating distant metastases. Both SUV and TMR were correlated with FAP expression (both r = 0.843, P < 0.001).
CONCLUSION
[Ga]Ga-DOTA-FAPI-04 PET/CT was superior to [F]FDG PET/CT in evaluating the World Health Organization (WHO) classification, MK staging, and metastatic status of TETs.
TRIAL REGISTRATION
ChiCTR2000038080, registration date 2020-09-09, https://www.chictr.org.cn/com/25/showproj.aspx?proj=61192.
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Gallium Radioisotopes; Thymoma; Thymus Neoplasms; Quinolines; Neoplasms, Glandular and Epithelial
PubMed: 37316675
DOI: 10.1007/s00259-023-06294-1 -
Clinical Advances in Hematology &... Oct 2023Positron emission tomography (PET)-based biologic radiation planning has the potential to improve tumor control by improving the accuracy of radiation delivery, allow... (Review)
Review
Positron emission tomography (PET)-based biologic radiation planning has the potential to improve tumor control by improving the accuracy of radiation delivery, allow for rational adaptive treatment, and decrease the likelihood of both acute and late side effects. 18F-fluorodeoxyglucose (FDG) PET is a widely used and effective diagnostic tool for many metabolically active tumors, including lymphoma and lung, head and neck, gastrointestinal, and gynecologic cancers. For these tumors, PET evidence has initially focused on more accurate staging but is evolving to allow for the escalation or deescalation of the radiotherapy dose depending on the PET-determined response to initial therapy. For gliomas and prostate cancer, novel tracers offer opportunities to improve tumor targeting of areas not well identified by traditional FDG PET. These tracers may also identify functional regions of healthy organs, allowing for more effective sparing of normal tissue.
Topics: Male; Humans; Fluorodeoxyglucose F18; Radiopharmaceuticals; Positron-Emission Tomography; Prostatic Neoplasms; Lymphoma; Head and Neck Neoplasms
PubMed: 37948591
DOI: No ID Found