[18F]-Fluorodeoxyglucose Uptake in Lymphoid Tissue Serves as a Predictor of Disease Outcome in the Nonhuman Primate Model of Monkeypox Virus Infection

ABSTRACT Real-time bioimaging of infectious disease processes may aid countermeasure development and lead to an improved understanding of pathogenesis. However, few studies have identified biomarkers for monitoring infections using in vivo imaging. Previously, we demonstrated that positron emission tomography/computed tomography (PET/CT) imaging with [18F]-fluorodeoxyglucose (FDG) can monitor monkeypox disease progression in vivo in nonhuman primates (NHPs). In this study, we investigated [18F]-FDG-PET/CT imaging of immune processes in lymphoid tissues to identify patterns of inflammation in the monkepox NHP model and to determine the value of [18F]-FDG-PET/CT as a biomarker for disease and treatment outcomes. Quantitative analysis of [18F]-FDG-PET/CT images revealed differences between moribund and surviving animals at two sites vital to the immune response to viral infections, bone marrow and lymph nodes (LNs). Moribund NHPs demonstrated increased [18F]-FDG uptake in bone marrow 4 days postinfection compared to surviving NHPs. In surviving, treated NHPs, increase in LN volume correlated with [18F]-FDG uptake and peaked 10 days postinfection, while minimal lymphadenopathy and higher glycolytic activity were observed in moribund NHPs early in infection. Imaging data were supported by standard virology, pathology, and immunology findings. Even with the limited number of subjects, imaging was able to differentiate the difference between disease outcomes, warranting additional studies to demonstrate whether [18F]-FDG-PET/CT can identify other, subtler effects. Visualizing altered metabolic activity at sites involved in the immune response by [18F]-FDG-PET/CT imaging is a powerful tool for identifying key disease-specific time points and locations that are most relevant for pathogenesis and treatment. IMPORTANCE Positron emission tomography and computed tomography (PET/CT) imaging is a universal tool in oncology and neuroscience. The application of this technology to infectious diseases is far less developed. We used PET/CT imaging with [18F]-labeled fluorodeoxyglucose ([18F]-FDG) in monkeys after monkeypox virus exposure to monitor the immune response in lymphoid tissues. In lymph nodes of surviving monkeys, changes in [18F]-FDG uptake positively correlated with enlargement of the lymph nodes and peaked on day 10 postinfection. In contrast, the bone marrow and lymph nodes of nonsurvivors showed increased [18F]-FDG uptake by day 4 postinfection with minimal lymph node enlargement, indicating that elevated cell metabolic activity early after infection is predictive of disease outcome. [18F]-FDG-PET/CT imaging can provide real-time snapshots of metabolic activity changes in response to viral infections and identify key time points and locations most relevant for monitoring the development of pathogenesis and for potential treatment to be effective.

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18F-FDG PET/CT Associates With Disease Activity and Clinical Recurrence of AOSD Patients

Frontiers in Medicine ◽

10.3389/fmed.2021.668323 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xian Li ◽

Chuning Dong ◽

Xiaowei Ma ◽

Yunhua Wang

Keyword(s):

Bone Marrow ◽

Lymph Nodes ◽

Disease Activity ◽

Influencing Factors ◽

Fdg Pet ◽

Metabolic Parameters ◽

Fdg Uptake ◽

Pet Ct ◽

Fdg Pet Ct ◽

Recurrence Group

Objective: The purpose of this study was to explore the value of 18F-FDG PET/CT in monitoring the disease activity and predicting the prognosis of the Adult-onset Still's disease (AOSD).Methods: We retrospectively analyzed the electronic medical records of 45 AOSD patients who underwent 18F-FDG PET/CT in the Second Xiangya Hospital. PET/CT imaging and clinical information were retrospectively reviewed and analyzed. 18F-FDG uptake was assessed by measuring standard uptake value (SUV) in the spleen, liver, bone marrow, and lymph nodes. The spleen-to-liver ratio of the SUVmax (SLRmax) and SUVmean (SLRmean), the bone-to-liver ratio of the SUVmax (BLRmax), and SUVmean (BLRmean), and the lymph nodes-to-liver ratio of the SUVmax (LyLRmax) were calculated. Clinical and laboratory information were collected and evaluated for association with metabolic parameters of 18F-FDG PET/CT. The influencing factors for recurrence within 1 year were analyzed to determine whether 18F-FDG PET/CT can predict the prognosis of AOSD patients.Results: Elevated 18F-FDG uptake could be observed in bone marrow, spleen, and lymph nodes of AOSD patients. Correlation analysis between 18F-FDG uptake of organs and laboratory examinations showed that SLRmean positively correlated with LDH, AST, ferritin, and the systemic score (r = 0.572, 0.353, 0.586, and 0.424, P < 0.05). The SLRmean had the highest correlation with ferritin (r = 0586, P < 0.001). All metabolic parameters in spleen, including SUVmax, SUVmean, SLRmax, and SLRmean, are positively correlated with LDH level (r = 0.405, 0.539, 0.481, and 0.572, P < 0.05). Bone marrow SUVmax, BLRmax, and BLRmean were correlated with C-reactive protein (CRP) level (r = 0.395, 0.437, and 0.469, P < 0.05). Analysis of the influencing factors of recurrence within 1 year showed that the spleen SUVmax, spleen SUVmean, SLRmax, SLRmean, ferritin, and the systemic score of the recurrence group was significantly higher than the non-recurrence group (P < 0.05). The SLRmean cutoff of 1.66 with a sensitivity of 72.7% and specificity of 80.0% had the highest performance in predicting recurrence.Conclusion: The glucose metabolism of the liver, spleen, and bone marrow of AOSD patients were correlated with laboratory inflammatory indicators and system score, suggesting that 18F-FDG PET/CT could be applied to evaluate disease activity. Moreover, spleen 18F-FDG uptake may be a potential biomarker for predicting clinical prognosis of AOSD patients.

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Quantitative analysis of myocardial metabolic heterogeneity is superior to visual assessment for the detection of active cardiac sarcoidosis by F-18 FDG PET-CT imaging

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.345 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

M Malik ◽

M Yazdani ◽

SM Gould ◽

E Reyes

Keyword(s):

Fdg Pet ◽

Cardiac Sarcoidosis ◽

Visual Assessment ◽

Ct Imaging ◽

Myocardial Inflammation ◽

Fdg Uptake ◽

Pet Ct ◽

Metabolic Heterogeneity ◽

Fdg Pet Ct

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial inflammation may occur in the context of a multisystem disease such as sarcoidosis, adversely affecting prognosis. A definitive diagnosis of cardiac sarcoidosis (CS) is essential to implementing life-saving treatment but this is complicated by the invasive nature of endomyocardial biopsy (EMB) and its low accuracy. Positron emission tomography (PET) assists in diagnosis, which relies on visual interpretation of myocardial F-18 FDG uptake. The value of quantitative analysis and its application to clinical practice remain uncertain. Purpose To investigate the power of quantitative F-18 FDG PET-CT imaging analysis for detecting CS in patients with suspected disease. Methods All patients underwent F-18 FDG PET-CT after a 24-hour low-carbohydrate diet and 15-hour fasting as part of their diagnostic work-up for suspected cardiac inflammation. Cardiovascular magnetic resonance acted as gatekeeper to PET-CT in 8 of every 10 scans. Myocardial F-18 FDG uptake was assessed qualitatively and quantitatively using both manually drawn regions of interest and automatic polar maps to measure global and segmental standardised F-18 FDG uptake values (SUV). The coefficient of variation (CoV) was calculated to determine uptake heterogeneity. To confirm diagnosis, follow-up data regarding disease progression, further testing and treatment were collected. To allow for sufficient follow-up time, the first 40 consecutive patients from a prospective registry (n= 214; Sep 2017-Jun 2020) were included. Results A comprehensive clinical picture was obtained successfully in 37 patients (median [IQR], 17 [13.5] months) and a final diagnosis of CS reached in 7 (disease prevalence, 19%). EMB was performed in 2 patients only while 3 underwent PPM/ICD implantation. Significant predictors of CS were fulfilment of Japanese Ministry of Health and Welfare criteria (Wald, 6.44; p = 0.01) and left ventricular dysfunction (Wald 6.72; p = 0.01). Qualitative F-18 FDG PET-CT had a high negative (95%) but low positive (45%) predictive value for CS (sensitivity, 83%; specificity, 77%). F-18 FDG SUV CoV was the strongest imaging predictor (Wald, 6.77; p = 0.009) and was significantly higher in CS than non-CS (CoV median [quartiles], 0.26 [0.21, 0.36] and 0.12 [0.11, 0.14] respectively; p = 0.004). As per ROC curve analysis (AUC, 0.84), a CoV threshold of 0.20 was highly specific (93%) and sensitive (86%) for CS. Conclusion In a referring population with a low prevalence of cardiac sarcoidosis, F-18 FDG PET-CT imaging is sensitive for the detection of myocardial inflammation with active disease unlikely in patients with a negative scan. Quantitative evaluation of metabolic heterogeneity within the myocardium provides a strong, independent marker of active disease and should be considered alongside visual assessment.

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Total metabolic lesion volume of lymph nodes measured by 18F-FDG PET/CT: a new predictor of macrophage activation syndrome in adult-onset Still’s disease

Arthritis Research & Therapy ◽

10.1186/s13075-021-02482-2 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Liyan Wan ◽

Yuting Gao ◽

Jieyu Gu ◽

Huihui Chi ◽

Zhihong Wang ◽

...

Keyword(s):

Bone Marrow ◽

Lymph Nodes ◽

Disease Severity ◽

Fdg Pet ◽

Macrophage Activation Syndrome ◽

Macrophage Activation ◽

Lesion Volume ◽

Pet Ct ◽

Fdg Pet Ct ◽

Activation Syndrome

Abstract Background To investigate the potential utility of quantitative parameters obtained by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the assessment of disease severity and the occurrence of macrophage activation syndrome (MAS) in adult-onset Still’s disease (AOSD). Methods Fifty-seven patients with AOSD who underwent pre-treatment 18F-FDG PET/CT were recruited in this study and compared with 60 age- and sex-matched healthy controls. Clinical features and laboratory data were recorded. The systemic score was assessed to determine the disease severity. The maximal standardized uptake value (SUVmax), metabolic lesion volume (MLV), and total lesion glycolysis (TLG) were used to evaluate the involved organs and tissues that abnormally accumulated 18F-FDG. Multivariate analysis was performed to identify the PET/CT-derived risk factors contributing to the AOSD-related MAS, and their diagnostic efficiency was evaluated. Results High 18F-FDG accumulation was observed in the bone marrow (SUVmax median, 5.10), spleen (SUVmax median, 3.70), and lymph nodes (LNs, SUVmax median, 5.55). The SUVmax of the bone marrow (rho = 0.376, p = 0.004), SUVmax of the spleen (rho = 0.450, p < 0.001), TLGtotal of LNs (rho = 0.386, p = 0.017), and MLVtotal of LNs (rho = 0.391, p = 0.015) were correlated with the systemic score. The SUVmax of the spleen (p = 0.017), TLGtotal of LNs (p = 0.045), and MLVtotal of LNs (p = 0.012) were higher in patients with MAS than in those without MAS. A MLVtotal of LNs > 62.2 (OR 27.375, p = 0.042) was an independent predictive factor for MAS with a sensitivity of 80.0% and a specificity of 93.9%. Conclusions The glucose metabolic level of the spleen could be an effective and easy-to-use imaging indicator of disease severity, and MLVtotal of LNs > 62.2 was a strong predictor of MAS occurrence in patients with AOSD.

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Anatomical MRI and [18F]FDG PET/CT imaging of Schistosoma mansoni in a NMRI mouse model

Scientific Reports ◽

10.1038/s41598-020-74226-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Tobias Lindner ◽

Jan Stenzel ◽

Nicole Koslowski ◽

Alexander Hohn ◽

Änne Glass ◽

...

Keyword(s):

Mouse Model ◽

Schistosoma Mansoni ◽

Fdg Pet ◽

Multimodal Imaging ◽

Organ Damage ◽

Ct Imaging ◽

Fdg Uptake ◽

Pet Ct ◽

Fdg Pet Ct ◽

Anatomical Mri

Abstract Schistosomiasis represents one of the most devastating worm parasitosis in the world. Current diagnostic methods are insufficient to determine the infection grade and the disease related organ damage. We herein investigated whether discrimination of infection grade and its correlation to liver damage could be accurately performed by multimodal imaging in a mouse model of Schistosoma mansoni infection. Therefore, groups of uninfected and infected mice underwent MRI and [18F]FDG PET/CT imaging. Anatomical MRI images were used for liver volumetry and for quantification of hepatic granulomas. For PET/CT images a volume of interest based analyses were employed to calculate the [18F]FDG uptake in liver, portal vein, spleen and abdomen. Herein, we demonstrate that the combined use of [18F]FDG-PET/CT and MRI represents an appropriate diagnostic tool for Schistosoma mansoni infection, but fails to discriminate the infection grade and the linked organ damage. Only the splenic [18F]FDG uptake in the 25 cercariae group (5.68 ± 0.90%ID/cc) and 50 cercariae group (4.98 ± 1.43%ID/cc) was significantly higher compared to the control group (2.13 ± 0.69%ID/cc). Nevertheless, future multimodal imaging studies with new radiopharmaceuticals could build a highly sensitive and specific basis for the diagnosis and evaluation of organ damage of schistosomiasis.

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Evaluation of thyroid FDG uptake incidentally identified on FDG-PET/CT imaging

Nuclear Medicine Communications ◽

10.1097/mnm.0b013e328324b431 ◽

2009 ◽

Vol 30 (3) ◽

pp. 240-244 ◽

Cited By ~ 79

Author(s):

Wengen Chen ◽

Molly Parsons ◽

Drew A. Torigian ◽

Hongming Zhuang ◽

Abass Alavi

Keyword(s):

Fdg Pet ◽

Ct Imaging ◽

Fdg Uptake ◽

Pet Ct ◽

Fdg Pet Ct

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Bone Marrow Metastasis Is an Early Stage of Bone Metastasis in Breast Cancer Detected Clinically by F18-FDG-PET/CT Imaging

BioMed Research International ◽

10.1155/2017/9852632 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Kusai M. Al-Muqbel

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Bone Metastasis ◽

Bone Metastases ◽

Fdg Pet ◽

Early Stage ◽

Ct Imaging ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

Objective. To determine the value of 18F-FDG PET/CT in detection of bone marrow (BM) metastasis in breast cancer which is considered an early stage of bone metastasis. Patients and Methods. Retrospectively, breast cancer patients with bone metastasis were included. BM metastasis was considered if the lesion was PET positive/CT occult while bone metastasis was considered if the lesion was PET positive/ CT positive. BM metastases were observed sequentially on F18-FDG PET/CT. Results. We included 35 patients. Eighteen patients (51%) had BM metastases in addition to other bone metastases. BM metastases comprised 24% of all lesions. Posttreatment scan was performed on 26/35 patients. Twenty-three percent of BM metastases had resolved completely without causing bone destruction after treatment. Sixty-five percent of BM metastases had converted into bone metastases after treatment. Twelve percent of BM metastases had persisted after treatment. Conclusion. This retrospective study showed clinically by 18F-FDG PET/CT imaging that BM metastasis is an early stage of bone metastasis in breast cancer. Interestingly, 18F-FDG-PET/CT showed that early eradication of individual BM metastasis by systemic treatment precluded development of bone metastasis. However, more research is needed to study the impact of an early diagnosis of BM metastases on treatment outcome.

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Conventionally-Defined and PET/CT-Defined Complete Response (CR) to Novel Agent-Based Induction Therapy and Autologous Stem-Cell Transplantation (ASCT) In Multiple Myeloma (MM): A Prospective Study of Clinical and Prognostic Implications

Blood ◽

10.1182/blood.v118.21.826.826 ◽

2011 ◽

Vol 118 (21) ◽

pp. 826-826

Author(s):

Elena Zamagni ◽

Cristina Nanni ◽

Francesca Patriarca ◽

Annalisa Pezzi ◽

Beatrice Anna Zannetti ◽

...

Keyword(s):

Bone Marrow ◽

Induction Therapy ◽

Fdg Pet ◽

Bone Marrow Involvement ◽

Trend Test ◽

Agent Based ◽

Fdg Uptake ◽

Pet Ct ◽

Fdg Pet Ct ◽

Time To Relapse

Abstract Abstract 826 Incorporation of novel agents into ASCT allowed the achievement of unprecedented high rates of CR in young MM patients, a gain which translated into extended PFS and OS. As a consequence, interest in the evaluation of the depth of CR has progressively grown. More sensitive tools, such as multiparametric flow cytometry or molecular biology, led to the demonstration of a correlation between the depth of CR and prognosis, but failed to identify the persistence of residual disease outside of the bone marrow level. 18 F-FDG PET/CT is a careful technique to detect with high sensitivity and specificity the presence of active bone lesions and/or bone marrow involvement in newly diagnosed and previously treated MM. We prospectively analysed the prognostic significance of FDG-PET/CT at diagnosis, after induction therapy and ASCT in an homogeneous population of 192 patients with newly diagnosed MM, followed for a median of 43 months. By study design, all patients were studied with FDG-PET/CT at baseline, after induction treatment, after 3 months from ASCT (single or double), once a year during the maintenance/follow-up phase and at time of relapse. Bone marrow involvement was described as negative, diffuse or focal. The number of focal lesions (FLs), as well as size and associated standardized uptake values (SUV) were recorded. Extra-medullary disease (EMD), if present, was described by location, size, number and SUV. Twenty four percent of the patients had a negative PET/CT scan at diagnosis. Among PET/CT-positive patients, 44% showed ≥3 FLs, 46% had SUV values >4.2 and in 6% EMD could be detected. These 3 variables adversely affected 4-year estimates of PFS and OS. In particular, both EMD and severe FDG uptake were significantly associated with shorter PFS and OS. Thirty seven percent of the patients were PET/CT-negative after induction. A strong correlation between conventional response and SUV max reduction was evident, the mean SUV value of patients achieving CR being significantly lower in comparison with that of patients reaching very good partial response (VGPR) or partial response (mean: 1.4 vs 3, respectively) (Cuzick's trend test, P= 0.016). Persistence of severe FDG uptake (SUV max still >4.2) after induction predicted for shorter PFS at 4 years (P= 0.004). PET/CT negativity (PET-CR) was observed in 65% of patients after 3 months from ASCT(s). A close relationship between PET/CT negativity and response to ASCT was evident, since 95% of patients with a negative PET/CT had achieved at least a VGPR (P= 0.003). Moreover, a correlation between conventional response and SUV max reduction was evident after ASCT as well (mean: 0.8 vs 1.8, respectively) (Cuzick's trend test, P= 0.001). PET-CR after ASCT conferred superior PFS and OS in comparison with persistence of FDG uptake. In particular, the 4-year estimates of PFS and OS for PET-CR patients were 66% and 89%, respectively, as compared with 45% and 65% for positive patients (P=0.02 both for PFS and OS). Notably, 23% of patients achieving CR according to conventional criteria still had positive PET/CT scans and their 4-year estimate of PFS was 30%, as compared with 61% for negative patients (P=0.02). After ASCT, patients were followed with evaluation of M protein every 3 months and of PET/CT once a year. In 44% of those who had a conventionally-defined relapse or progression, the mean time to relapse/progression was 27.6 months for PET-negative patients as compared with 18 months for positive patients (P=0.05). In PET-positive patients, the SUV max was inversely correlated to the time to relapse (correlation coefficient −0.7, P= 0.003). In multivariate analysis, both severe PET/CT involvement at diagnosis (SUV >4.2 and/or EMD) and persistence of FDG uptake after ASCT were independent predictors of worst PFS (SUV >4.2= HR: 2.0, 95%CI: 1.13–3.72; EMD= HR: 15.0, 4.0–55.8; FDG uptake after ASCT= HR: 2.12, 1.19–3.77) and OS (EMD= HR: 6.99, 2.28–21.46; FDG uptake after ASCT= HR: 3.57, 1.03–12.39). In conclusion, PET-defined CR was linked to conventionally-defined CR and was an independent prognostic factor in MM patients receiving up-front novel agent-based induction therapy and ASCT. PET/CT contributed to a more careful definition of CR, in particular after ASCT, and could be usefully incorporated into the algorithm to evaluate the depth of response in young MM patients. Disclosures: No relevant conflicts of interest to declare.

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