scholarly journals SAT0551 WHOLE BODY MACROPHAGE PET IMAGING THAT INCLUDES THE FEET CAN PROVIDE ADDITIONAL INFORMATION TO CLINICAL ASSESSMENT IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1233.2-1233
Author(s):  
N. J. F. Verweij ◽  
M. Ter Wee ◽  
J. De Jongh ◽  
G. C. J. Zwezerijnen ◽  
M. Yaqub ◽  
...  

Background:Clinical assessment of arthritis is the cornerstone in the diagnosis and treatment of rheumatoid arthritis (RA). Nevertheless, reliable determination of (sub)clinical arthritis can be difficult, especially in the feet. Advanced imaging techniques may contribute to early diagnosis and therapy monitoring through sensitive detection and (quantitative) monitoring of synovitis. Previously, it has been demonstrated that macrophage imaging using (R)-[11C]PK11195 positron emission tomography (PET) allows for highly sensitive and specific imaging of RA disease activity in the hands.(1,2)Whole body macrophage PET imaging that includes the feet has not yet been evaluated in RA.Objectives:To compare whole body macrophage PET imaging to clinical assessment of arthritis activity in clinically active, early RA patients.Methods:Thirty-five previously untreated RA patients (age 54 ± 12, 51% male) with at least two clinically inflamed joints were included. They underwent a whole body (R)-[11C]PK11195 PET/computed tomography (CT) scan in addition to standard clinical assessment of number of tender and swollen joints (TJC and SJC, respectively). Two readers blinded to clinical assessment (GZ and CvdL) visually scored intensity of uptake in joints on a 0 to 3 scale. A PET positive joint score was defined at ≥ 1. Additionally, (R)-[11C]PK11195 uptake in joints was assessed quantitatively as standardized uptake values (SUV). Visual parameters were compared to clinical parameters using Cohen’s kappa, and quantitative parameters were analyzed using an independent T-test.Results:All patients showed enhanced tracer uptake in one or more joints (Figure 1). A total of 168 joints were visually PET positive, with the following distribution: 16% in the wrists, 14% in the metacarpophalangeal joints, 25% in the proximal interphalangeal joints, 4% in the ankles, 37% in the metatarsophalangeal joints. Positivity in other large joints was rare (4%). The number of discrepant findings between PET and clinical outcome (TJC and/or SJC) varied based on anatomic localization; more joints were clinically active in the hands, and more joints were active on the PET scan in the feet. Consequently, agreement between visual PET positivity and clinical activity was low, with only moderate agreement found in the ankles (κ = 0.46 and 0.41 for SJC and TJC respectively). Quantitative PET data showed a trend towards higher SUV values in joints that were clinically tender and/or swollen, reaching a significant difference in the feet (ankles + MTPs) versus SJC (Figure 2; 0.7 vs 1.0,p< 0.001). However, parts of the clinically non-affected joints also depicted moderately increased SUV values, and vice versa.Figure 1.Visual PET uptake in the left MTP5-joint.Figure 2.(R)-[11C]PK11195 (SUV) in both clinically affected and non-affected feet joints (defined as swollen yes or no).Conclusion:Whole body macrophage PET imaging showed clear uptake of (R)-[11C]PK11195 in several joints of clinically active, early RA patients, especially in MTP-joints. The best correlation between quantitative PET data and clinical assessment of swelling was observed in the feet. In general, however, PET also provided distinct information from clinical assessment, which may provide a means for detecting subclinical synovitis. We are performing longitudinal studies to further assess the value of macrophage PET in RA.References:[1]Elzinga EH, et al. J Nucl Med. 2011; 52(1): 77-80.[2]Gent YY, et al. J Rheumatology. 2014; 41: 2145-52Acknowledgments:We thank ReumaNederland and Pfizer for financial support of this investigator initiated study.Disclosure of Interests:Nicki J.F. Verweij: None declared, Marieke ter Wee: None declared, Jerney de Jongh: None declared, Gerben C.J. Zwezerijnen: None declared, Maqsood Yaqub: None declared, Maarten Boers: None declared, Alexandre Voskuyl: None declared, Adriaan A. Lammertsma: None declared, WIllem Lems Grant/research support from: Pfizer, Consultant of: Lilly, Pfizer, Conny J. van der Laken: None declared

2019 ◽  
Vol 47 (5) ◽  
pp. 1302-1313 ◽  
Author(s):  
Camilla Christensen ◽  
Lotte K. Kristensen ◽  
Maria Z. Alfsen ◽  
Carsten H. Nielsen ◽  
Andreas Kjaer

Abstract Purpose Despite remarkable clinical responses and prolonged survival across several cancers, not all patients benefit from PD-1/PD-L1 immune checkpoint blockade. Accordingly, assessment of tumour PD-L1 expression by immunohistochemistry (IHC) is increasingly applied to guide patient selection, therapeutic monitoring, and improve overall response rates. However, tissue-based methods are invasive and prone to sampling error. We therefore developed a PET radiotracer to specifically detect PD-L1 expression in a non-invasive manner, which could be of diagnostic and predictive value. Methods Anti-PD-L1 (clone 6E11, Genentech) was site-specifically conjugated with DIBO-DFO and radiolabelled with 89Zr (89Zr-DFO-6E11). 89Zr-DFO-6E11 was optimized in vivo by longitudinal PET imaging and dose escalation with excess unlabelled 6E11 in HCC827 tumour-bearing mice. Specificity of 89Zr-DFO-6E11 was evaluated in NSCLC xenografts and syngeneic tumour models with different levels of PD-L1 expression. In vivo imaging data was supported by ex vivo biodistribution, flow cytometry, and IHC. To evaluate the predictive value of 89Zr-DFO-6E11 PET imaging, CT26 tumour-bearing mice were subjected to external radiation therapy (XRT) in combination with PD-L1 blockade. Results 89Zr-DFO-6E11 was successfully labelled with a high radiochemical purity. The HCC827 tumours and lymphoid tissue were identified by 89Zr-DFO-6E11 PET imaging, and co-injection with 6E11 increased the relative tumour uptake and decreased the splenic uptake. 89Zr-DFO-6E11 detected the differences in PD-L1 expression among tumour models as evaluated by ex vivo methods. 89Zr-DFO-6E11 quantified the increase in PD-L1 expression in tumours and spleens of irradiated mice. XRT and anti-PD-L1 therapy effectively inhibited tumour growth in CT26 tumour-bearing mice (p < 0.01), and the maximum 89Zr-DFO-6E11 tumour-to-muscle ratio correlated with response to therapy (p = 0.0252). Conclusion PET imaging with 89Zr-DFO-6E11 is an attractive approach for specific, non-invasive, whole-body visualization of PD-L1 expression. PD-L1 expression can be modulated by radiotherapy regimens and 89Zr-DFO-6E11 PET is able to monitor these changes and predict the response to therapy in an immunocompetent tumour model.


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying-Qian Mo ◽  
Ze-Hong Yang ◽  
Jun-Wei Wang ◽  
Qian-Hua Li ◽  
Xin-Yun Du ◽  
...  

Abstract Background Bilateral hands including proximal interphalangeal joints (PIPJs) are recommended on physical, X-ray radiographic, or ultrasonographic examination by clinical guidelines of rheumatoid arthritis (RA), but MRI still tends to examine unilateral wrists and/or MCPJs. We aimed to demonstrate the advantages of MRI examination on bilateral hands including PIPJs for disease assessment in early RA patients. Methods Active early RA patients received 3.0T whole-body MRI examination with contrast-enhanced imaging on bilateral wrists, MCPJs, and PIPJs. MRI features were scored referring to the updated RAMRIS. Clinical assessments were conducted on the day of MRI examination. Results The mean time of MRI examination was 24 ± 3 min. MRI bone erosion in MCPJs would be missed-diagnosed in 23% of patients if non-dominant MCPJs were scanned unilaterally, while osteitis in MCPJs would be missed-diagnosed in 16% of patients if dominant MCPJs were scanned unilaterally. MRI synovitis severity was also asymmetric: 21% of patients showing severe synovitis unilaterally in non-dominant MCPJs/PIPJs and other 20% showing severe synovitis unilaterally in dominant MCPJs/PIPJs. Among these early RA patients, MRI tenosynovitis occurred the most frequently in wrist extensor compartment I, while MRI examination on bilateral hands demonstrated no overuse influence present. However, overuse should be considered in dominant PIPJ2, PIPJ4, and IPJ of thumb of which MRI tenosynovitis prevalence was respectively 18%, 17%, or 16% higher than the non-dominant counterparts. Early MRI abnormality of nervus medianus secondary to severe tenosynovitis occurred either in dominant or non-dominant wrists; MRI of unilateral hands would take a risk of missed-diagnosis. Common MRI findings in PIPJs were synovitis and tenosynovitis, respectively in 87% and 69% of patients. MRI tenosynovitis prevalence in IPJ of thumb or PIPJ5 was much higher than the continued wrist flexor compartments. MRI synovitis or tenosynovitis in PIPJs independently increased more than twice probability of joint tenderness (OR = 2.09 or 2.83, both p < 0.001). Conclusions In consideration of asymmetric MRI features in early RA, potential overuse influence for certain tenosynovitis in dominant hands, and high prevalence of MRI findings in PIPJs, MRI examination on bilateral hands including PIPJs is deserved for disease assessment in early RA patients.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Anna Södergren ◽  
Kjell Karp ◽  
Christine Bengtsson ◽  
Bozena Möller ◽  
Solbritt Rantapää-Dahlqvist ◽  
...  

Objective. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker of vascular inflammation, is associated with cardiovascular disease. This prospective study of an inception cohort aimed to investigate whether the level of Lp-PLA2 is associated with subclinical atherosclerosis in patients with rheumatoid arthritis (RA).Methods. Patients from northern Sweden diagnosed with early RA were consecutively recruited into an ongoing prospective study. From these, all patients ≤60 years (n=71) were included for measurements of subclinical atherosclerosis at inclusion (T0) and five years later (T5). Forty age- and sex-matched controls were included. The patients were clinically assessed, SCORE, Reynolds Risk Score, and Larsen score were calculated, and blood samples were drawn from all individuals at T0 and T5.Results. There was no significant difference in the level of Lp-PLA2 between patients with RA and controls (p>0.05). In simple linear regression models among patients with RA, Lp-PLA2 at T0 was significantly associated with intima media thickness (IMT) at T0 and T5, flow mediated dilation (FMD) at T0 and T5, ever smoking, male sex, HDL-cholesterol (inversely), non-HDL-cholesterol, SCORE, Reynolds Risk Score, and Larsen score (p<0.05).Conclusion. In this cohort of patients with early RA, the concentration of Lp-PLA2 was associated with both subclinical atherosclerosis and disease severity.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 503.2-504
Author(s):  
Y. W. Zou ◽  
C. Chen ◽  
Q. Zhang ◽  
S. Y. Lian ◽  
K. M. Yang ◽  
...  

Background:Rheumatoid arthritis (RA) is a leading cause of extremity disability in Chinese female population according to 2006 national survey. However, less epidemiological data about functional limitation in Chinese RA patients have been published.Objectives:To investigate the prevalence, characteristics and associated factors of functional limitation in Chinese RA patients.Methods:Consecutive patients with RA were recruited. The demographic and clinical data were collected including indicators of disease activity, functional assessment and radiographic assessment. According to Health Assessment Questionnaire Disease Index (HAQ-DI), functional limitation was defined as: mild (0 < HAQ-DI ≤ 1), moderate (1 < HAQ-DI ≤ 2), and severe (2 < HAQ-DI ≤ 3).Results:There were 643 RA patients recruited with 82.3% female and mean age 49.7 ± 12.9 years. The median (IQR) of total HAQ-DI was 0.25 (0.00-0.75) and there were 399 (62.1%) RA patients with functional limitation including 293 (45.6%), 73 (11.4%), 33 (5.1%) with mild, moderate, and severe functional limitation, respectively. The highest prevalence of functional limitation subdimension was ‘‘walking’’ (43.5%), followed by “grip” (36.1%), ‘‘reach’’ (35.5%), ‘‘common daily activities’’ (33.4%), ‘‘hygiene’’ (33.0%), ‘‘dressing and grooming’’ (29.7%), ‘‘arising’’ (29.1%), while the lowest was ‘‘eating’’ (18.4%). Further age stratification showed that the prevalence of functional limitation was increased with age (P < 0.001), but no difference between male and female RA patients (58.8% vs. 62.8%, P = 0.426). The prevalence of functional limitation of RA patients with disease duration < 1 years (early), 1-10 years (intermediate) and ≥ 10 years (long) were 70.2%, 55.9% and 74.5% respectively, showing a U-shaped curve (Figure 1A), which indicated that early RA also had high rate of functional limitation. Furthermore, early RA patients had the highest proportion of severe functional limitation (14.3% vs. 2.0% vs. 8.7%, Figure 1B), together with higher prevalence of functional limitation of all eight subdimension than those with intermediate disease duration (P < 0.05, Figure 1C). There were significant differences in Pain VAS, indicators of disease activity, functional and radiographic assessment among RA patients with different disease duration. Compared with those with intermediate disease duration, early RA patients had higher Pain VAS, higher disease activity indicator (including ESR, CRP, CDAI), higher HAQ-DI, but lower radiographic indicators (all P < 0.05). There was no significant difference in disease activity and functional indicators between early RA patients and those with long disease duration. Multivariate ordered logistic regression analysis showed that Pain VAS (OR = 2.116, 95% CI: 1.483-3.019), disease activity indicators [including CRP (OR = 1.047, 95% CI: 1.011-1.084) and CDAI (OR = 1.128, 95% CI: 1.054-1.208)] were associated factors of functional limitation in early RA patients.Figure 1.The prevalence of function limitation in RA patients. (A) The prevalence of functional limitation in different disease duration groups of RA patients. (B) The different degrees of functional limitation in different disease duration groups of RA patients. (C) The subdimension characteristics of functional limitation in different disease duration groups of RA patients.Conclusion:Near two third early RA patients have functional limitation, in which both pain and active disease are independent associated factors. Management of pain and target treatment in early RA patients should be emphasized.Fund program:National Natural Science Foundation of China (81801605, 81801606, 81971527); Guangdong Natural Science Foundation (2018A030313541, 2018A030313690, 2019A1515011928); Guangzhou Science and Technology Program (201904010088); Guangdong Basic and Applied Basic Research Foundation (2020A1515110061); Guangdong Medical Scientific Research Foundation (A2018062)Disclosure of Interests:None declared


2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii66-iii66
Author(s):  
H Takei ◽  
J Shinoda ◽  
S Ikuta ◽  
T Maruyama ◽  
Y Muragaki ◽  
...  

Abstract BACKGROUND Positron emission tomography (PET) is important in noninvasive diagnostic imaging of gliomas. There are many PET studies on glioma diagnosis based on the 2007 World Health Organization (WHO) classification; however, there are no studies on glioma diagnosis using the new classification (the 2016 WHO classification).Here we investigated the relationship between PET imaging using 11C-methionine (MET), 11C-choline (CHO), and 18F-fluorodeoxyglucose (FDG) and wildtype isocitrate dehydrogenase (IDH) (IDH-wt)/mutant IDH (IDH-mut) in astrocytic and oligodendroglial tumors according to the 2016 WHO classification. MATERIAL AND METHODS In total, 105 patients with newly diagnosed cerebral gliomas (six diffuse astrocytomas [DAs] with IDH-wt, six DAs with IDH-mut, seven anaplastic astrocytomas [AAs] with IDH-wt, 24 AAs with IDH-mut, 26 glioblastomas [GBMs] with IDH-wt, five GBMs with IDH-mut, 19 oligodendrogliomas [ODs], and 12 anaplastic oligodendrogliomas [AOs]) were included. All OD and AO patients had both IDH-mut and 1p/19q codeletion. The maximum standardized uptake values (SUVs) of the tumor/normal cortex mean SUV ratios (T/N ratios) for MET, CHO, and FDG were calculated; the mean T/N ratios of DA, AA, and GBM with IDH-wt/IDH-mut were compared. The diagnostic accuracy for distinguishing gliomas with IDH-wt from those with IDH-mut was assessed using receiver operating characteristic (ROC) curve analysis of the mean T/N ratios for the three PET tracers. RESULTS There were significant differences in the mean T/N ratios for all three PET tracers between the IDH-wt and IDH-mut groups including all histological classifications (p<0.001). Among the 27 gliomas with mean T/N ratios higher than the cutoff values for all three PET tracers, 23 (85.2%) were classified into the IDH-wt group using ROC analysis. In DA, there were no significant differences in the T/N ratios for MET, CHO, and FDG between the IDH-wt and IDH-mut groups. In AA, the mean T/N ratios of all three PET tracers in the IDH-wt group were significantly higher than those in the IDH-mut group (p<0.001). In GBM, the mean T/N ratio in the IDH-wt group was significantly higher than that of the IDH-mut group for both MET (p=0.034) and CHO (p=0.01). However, there was no significant difference in the ratio for FDG. CONCLUSIONS PET imaging using MET, CHO, and FDG was confirmed to be informative for preoperatively differentiating gliomas according to the 2016 WHO classification, particularly for differentiating IDH-wt and IDH-mut tumors.


2005 ◽  
Vol 44 (S 01) ◽  
pp. S51-S57 ◽  
Author(s):  
T. Beyer ◽  
G. Brix

Summary:Clinical studies demonstrate a gain in diagnostic accuracy by employing combined PET/CT instead of separate CT and PET imaging. However, whole-body PET/CT examinations result in a comparatively high radiation burden to patients and thus require a proper justification and optimization to avoid repeated exposure or over-exposure of patients. This review article summarizes relevant data concerning radiation exposure of patients resulting from the different components of a combined PET/CT examination and presents different imaging strategies that can help to balance the diagnostic needs and the radiation protection requirements. In addition various dose reduction measures are discussed, some of which can be adopted from CT practice, while others mandate modifications to the existing hardand software of PET/CT systems.


Author(s):  
Abeer Fauzi Al-Rubaye ◽  
Mohanad Jawad Kadhim ◽  
Imad Hadi Hameed

The pharmacological mechanisms of the medicinal plants traditionally used for RA in Persian medicine are discussed in the current review. Further investigations are mandatory to focus on bioefficacy of these phytochemicals for finding novel natural drugs. Rheumatoid arthritis is chronic, progressive, disabling autoimmune disease characterized by systemic inflammation of joints, damaging cartilage and bone around the joints. It is a systemic disease which means that it can affect the whole body and internal organs such as lungs, heart and eyes. Although numbers of synthetic drugs are being used as standard treatment for rheumatoid arthritis but they have adverse effect that can compromise the therapeutic treatment. Unfortunately, there is still no effective known medicinal treatment that cures rheumatoid arthritis as the modern medicine can only treat the symptoms of this disease that means to relieve pain and inflammation of joints. It is possible to use the herbs and plants in various forms in order to relieve the pain and inflammation in the joints. There are so many medicinal plants that have shown anti rheumatoid arthritis properties. So the plants and plant product with significant advantages are used for the treatment of rheumatoid arthritis. The present review is focused on the medicinal plants having anti rheumatoid arthritis activity


2020 ◽  
Author(s):  
Lucas S. Ryan ◽  
Jeni Gerberich ◽  
Uroob Haris ◽  
ralph mason ◽  
Alexander Lippert

<p>Regulation of physiological pH is integral for proper whole-body and cellular function, and disruptions in pH homeostasis can be both a cause and effect of disease. In light of this, many methods have been developed to monitor pH in cells and animals. In this study, we report a chemiluminescence resonance energy transfer (CRET) probe Ratio-pHCL-1, comprised of an acrylamide 1,2-dioxetane chemiluminescent scaffold with an appended pH-sensitive carbofluorescein fluorophore. The probe provides an accurate measurement of pH between 6.8-8.4, making it viable tool for measuring pH in biological systems. Further, its ratiometric output is independent of confounding variables. Quantification of pH can be accomplished both using common fluorimetry and advanced optical imaging methods. Using an IVIS Spectrum, pH can be quantified through tissue with Ratio-pHCL-1, which has been shown in vitro and precisely calibrated in sacrificed mouse models. Initial studies showed that intraperitoneal injections of Ratio-pHCL-1 into sacrificed mice produce a photon flux of more than 10^10 photons per second, and showed a significant difference in ratio of emission intensities between pH 6.0, 7.0, and 8.0.</p> <b></b><i></i><u></u><sub></sub><sup></sup><br>


2020 ◽  
Vol 133 (4) ◽  
pp. 1010-1019 ◽  
Author(s):  
Hiroaki Takei ◽  
Jun Shinoda ◽  
Soko Ikuta ◽  
Takashi Maruyama ◽  
Yoshihiro Muragaki ◽  
...  

OBJECTIVEPositron emission tomography (PET) is important in the noninvasive diagnostic imaging of gliomas. There are many PET studies on glioma diagnosis based on the 2007 WHO classification; however, there are no studies on glioma diagnosis using the new classification (the 2016 WHO classification). Here, the authors investigated the relationship between uptake of 11C-methionine (MET), 11C-choline (CHO), and 18F-fluorodeoxyglucose (FDG) on PET imaging and isocitrate dehydrogenase (IDH) status (wild-type [IDH-wt] or mutant [IDH-mut]) in astrocytic and oligodendroglial tumors according to the 2016 WHO classification.METHODSIn total, 105 patients with newly diagnosed cerebral gliomas (6 diffuse astrocytomas [DAs] with IDH-wt, 6 DAs with IDH-mut, 7 anaplastic astrocytomas [AAs] with IDH-wt, 24 AAs with IDH-mut, 26 glioblastomas [GBMs] with IDH-wt, 5 GBMs with IDH-mut, 19 oligodendrogliomas [ODs], and 12 anaplastic oligodendrogliomas [AOs]) were included. All OD and AO patients had both IDH-mut and 1p/19q codeletion. The maximum standardized uptake value (SUV) of the tumor/mean SUV of normal cortex (T/N) ratios for MET, CHO, and FDG were calculated, and the mean T/N ratios of DA, AA, and GBM with IDH-wt and IDH-mut were compared. The diagnostic accuracy for distinguishing gliomas with IDH-wt from those with IDH-mut was assessed using receiver operating characteristic (ROC) curve analysis of the mean T/N ratios for the 3 PET tracers.RESULTSThere were significant differences in the mean T/N ratios for all 3 PET tracers between the IDH-wt and IDH-mut groups of all histological classifications (p < 0.001). Among the 27 gliomas with mean T/N ratios higher than the cutoff values for all 3 PET tracers, 23 (85.2%) were classified into the IDH-wt group using ROC analysis. In DA, there were no significant differences in the T/N ratios for MET, CHO, and FDG between the IDH-wt and IDH-mut groups. In AA, the mean T/N ratios of all 3 PET tracers in the IDH-wt group were significantly higher than those in the IDH-mut group (p < 0.01). In GBM, the mean T/N ratio in the IDH-wt group was significantly higher than that in the IDH-mut group for both MET (p = 0.034) and CHO (p = 0.01). However, there was no significant difference in the ratio for FDG.CONCLUSIONSPET imaging using MET, CHO, and FDG was suggested to be informative for preoperatively differentiating gliomas according to the 2016 WHO classification, particularly for differentiating IDH-wt and IDH-mut tumors.


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