Clinical value of whole-body PET/CT in patients with active rheumatic diseases

Advanced imaging techniques may enable early diagnosis and monitoring of therapy in various rheumatic diseases. To prevent irreversible tissue damage, inflammatory rheumatic disease must be diagnosed and treated in pre-clinical stages, requiring highly sensitive detection techniques. Positron emission tomography (PET) provides highly sensitive, quantitative imaging at a molecular level, revealing the important pathophysiological processes underlying inflammation. This review provides an overview of the current utility of ¹⁸ F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in patients with active rheumatic diseases such as rheumatoid arthritis, spondyloarthritis, polymyalgia rheumatica, adult-onset Still’s disease, relapsing polychondritis, immunoglobulin G4-related disease, large-vessel vasculitis, Wegener’s granulomatosis, polymyositis, and dermatomyositis. We also discuss the role of FDG-PET/CT in the diagnosis and monitoring of these diseases.     

Clinical value of (18)F-FDG PET/CT in postoperative monitoring for patients with colorectal carcinoma

Objective: To evaluate the clinical value of ¹⁸F-FDG PET/CT in postoperative monitoring for patients with colorectal carcinoma. Methods: 66 postoperative patients with colorectal carcinoma underwent whole-body FDG PET/CT. The final histopathological and formal clinical follow-up findings were used as gold standard to determine the sensitivity and specificity of FDG PET/CT and enhanced CT of the same periods. Results: The sensitivity and specificity of FDG PET/CT in detecting recurrence are 96.30%, 94.87% (while enhanced CT are 70.37% and 87.18% respectively). The sensitivity and specificity in detecting metastasis are 95.35%, 82.61% (enhanced CT are 61.90%, 75.00%). SUVmax was significantly higher in malignant lesions [range 4.16–22.00, mean ± standard deviation (x ± s) 8.06 ± 4.30] than in benign ones (range1.18–6.25, x ± s 2.82 ± 1.02). Conclusion: At present, whole-body ¹⁸F-FDG PET/CT is an advanced diagnostic imaging technique in detecting loco-regional recurrence and metastasis in postoperative patients with colorectal carcinoma for its higher sensitivity and specificity.     

Renal co-morbidity in patients with rheumatic diseases

Renal co-morbidity is common in patients with rheumatic disease based on regular assessment of serum and urine parameters of renal function. When patients present with both arthritis and renal abnormalities the following questions have to be addressed. Is kidney disease a complication of rheumatic disease or its management, or are they both manifestations of a single systemic autoimmune disease? Is rheumatic disease a complication of kidney disease and its management? How do rheumatic disease and kidney disease affect each other even when they are unrelated? The present review provides an overview of how to address these questions in daily practice.     

Cardiovascular co-morbidity in patients with rheumatic diseases

During recent years atherosclerosis, the major cause of cardiovascular disease (CVD), has been recognised as a chronic inflammatory condition in which rupture of atherosclerotic lesions appears to play a major role. The risk of CVD is raised in many rheumatic diseases. This risk is high in systemic lupus erythematosus - as much as a 50-times increase among middle-aged women has been reported. Studies on CVD and atherosclerosis in rheumatic disease could thus provide interesting information about CVD and atherosclerosis in addition to being an important clinical problem. A combination of traditional and nontraditional risk factors accounts for the increased risk of CVD and atherosclerosis in rheumatic disease. One interesting possibility is that atherosclerotic lesions in rheumatic disease are more prone to rupture than normal atherosclerotic lesions. It is also likely that increased risk of thrombosis may play an important role, not least in systemic lupus erythematosus. Further, it is not clear whether an increased risk of CVD is a general feature of rheumatic disease, or whether this only occurs among subgroups of patients. It should be emphasised that there is an apparent lack of treatment studies where CVD in rheumatic disease is the end point. Control of disease activity and of traditional risk factors, however, appears to be well founded in relation to CVD in rheumatic disease. Further studies are needed to determine the exact role of lipid-lowering drugs as statins. Hopefully novel therapies can be developed that target the causes of the inflammation in atherosclerotic lesions both in rheumatic patients and in the general population.     

Renal co-morbidity in patients with rheumatic diseases

Renal co-morbidity is common in patients with rheumatic disease based on regular assessment of serum and urine parameters of renal function. When patients present with both arthritis and renal abnormalities the following questions have to be addressed. Is kidney disease a complication of rheumatic disease or its management, or are they both manifestations of a single systemic autoimmune disease? Is rheumatic disease a complication of kidney disease and its management? How do rheumatic disease and kidney disease affect each other even when they are unrelated? The present review provides an overview of how to address these questions in daily practice.     

Ultra-low dose whole-body CT for attenuation correction in a dual tracer PET/CT protocol for multiple myeloma

PurposeTo investigate within phantoms the minimum CT dose allowed for accurate attenuation correction of PET data and to quantify the effective dose reduction when a CT for this purpose is incorporated in the clinical setting.MethodsThe NEMA image quality phantom was scanned within a large parallelepiped container. Twenty-one different CT images were acquired to correct attenuation of PET raw data. Radiation dose and image quality were evaluated.Thirty-one patients with proven multiple myeloma who underwent a dual tracer PET/CT scan were retrospectively reviewed. ¹⁸F-fluorodeoxyglucose PET/CT included a diagnostic whole-body low dose CT (WBLDCT: 120 kV-80mAs) and ¹¹C-Methionine PET/CT included a whole-body ultra-low dose CT (WBULDCT) for attenuation correction (100 kV-40mAs). Effective dose and image quality were analysed.ResultsOnly the two lowest radiation dose conditions (80 kV-20mAs and 80 kV-10mAs) produced artifacts in CT images that degraded corrected PET images. For all the other conditions (CTDI_vol ≥ 0.43 mGy), PET contrast recovery coefficients varied less than ± 1.2%.Patients received a median dose of 6.4 mSv from diagnostic CT and 2.1 mSv from the attenuation correction CT. Despite the worse image quality of this CT, 94.8% of bone lesions were identifiable.ConclusionPhantom experiments showed that an ultra-low dose CT can be implemented in PET/CT procedures without any noticeable degradation in the attenuation corrected PET scan. The replacement of the standard CT for this ultra-low dose CT in clinical PET/CT scans involves a significant radiation dose reduction.     

早期肺癌诊断中PET/CT的应用价值

目的:探讨PET/CT在早期肺癌诊断中的应用价值.方法:应用PET/CT对16例肺部孤立性病灶进行PET/CT检查,手术切除病灶组织送病理检查,以判断诊断符合率与细胞类型.结果:16例肺病灶患者PET/CT检查与手术切除组织病理结果相比较,诊断符合率为87.5%,其中腺癌13例(包括细支气管肺泡细胞癌6例),鳞癌2例,肺粘膜相关B细胞淋巴瘤1例.结论:结合临床症状,PET/CT检查能够准确的对肺癌做出早期诊断,及早治疗,改善患者预后     

Equivalent dose rate from patients after whole-body FDG-PET/CT

Introduction

¹⁸F-fluorodeoxyglucose PET/CT (FDG-PET/CT) is an imaging modality routinely used in oncology, hematology, as well as in infectious and inflammatory diseases. Frequently, patients and their accompanying persons may be apprehensive concerning risks of radiation exposure after performing this examination, particularly when it concerns nearby young adolescents or pregnant women. Our objective was to clearly explain about radiation protection instructions for patients after performing whole-body FDG-PET/CT based on the Equivalent Dose Rate (EDR) estimation at our nuclear medicine department.

BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases

BLyS and APRIL are two members of the TNF superfamily that are secreted by activated myeloid cells and have costimulatory activity on B cells. BLyS and APRIL share two receptors, TACI and BCMA, whereas a third receptor, BAFF-R, specifically binds BLyS. Both BLyS and APRIL have been described as homotrimeric molecules, a feature common to members of the TNF superfamily. In this study, we show that APRIL and BLyS can form active heterotrimeric molecules when coexpressed and that circulating heterotrimers are present in serum samples from patients with systemic immune-based rheumatic diseases. These findings raise the possibility that active BLyS/APRIL heterotrimers may play a role in rheumatic and other autoimmune diseases and that other members of the TNF ligand superfamily may also form active soluble heterotrimers.     

Clinical relevance of autoantibodies in systemic rheumatic diseases

Autoantibodies directed to intracellular antigens are serological hallmarks of systemic rheumatic diseases. Identification of circulating autoantibodies is helpful in establishing the correct diagnosis, indicating the prognosis and providing a guide to treatment and follow-up. Some autoantibodies are included in diagnostic and classification criteria for diseases such as anti-Sm antigen and anti-double-stranded DNA antibodies in systemic lupus erythematosus, anti-U1 nuclear ribonucleoprotein antibodies in mixed connective tissue disease, and anti-SS-A/Ro and anti-SS-B/La antibodies in Sjögren's syndrome. Over the past 30 years, the identification of new autoantibody systems was advanced by the initiation or adaptation of novel techniques such as double immunodiffusion to detect antibodies to saline-soluble nuclear antigens, extraction-reconstitution and ELISA techniques to detect histone and chromatin antibodies, immunoblotting and immunoprecipitation to detect a wide range of antibodies directed against naturally occurring and recombinant proteins. These techniques have been made possible by advances in cellular and molecular biology and in turn, the sera from index patients have been important reagents to identify novel intracellular macromolecules. This paper will focus on the clinical relevance of several autoantibody systems described by Tan and his colleagues over the past 30 years.Abbreviations ANA antinuclear antibody - CENPs centromere proteins - CTD connective tissue disease - DIA drug-induced autoimmunity - DIL drug-induced lupus - HIV human immunodeficiency virus - IIF indirect immunofluorescence - JCA juvenile chronic arthritis - MCTD mixed connective tissue disease - MSA mitotic spindle apparatus - NOR nucleolar organizer - NuMA nuclear mitosis antigen - PBC primary biliary cirrhosis - PCNA proliferating cell nuclear antigen - PM polymyositis - RA rheumatoid arthritis - RNP ribonucleoprotein - SLE systemic lupus erythematosus - SS Sjögren's syndrome - SSc systemic sclerosis - UCTD undifferentiated connective tissue disease     

Radiobiological risks in terms of effective dose and organ dose from 18F-FDG whole-body PET/CT procedures

IntroductionIntegrated Positron Emission Tomography (PET) with Computerized tomography (CT) (PET/CT) are widely used to diagnose, stage and track human diseases during whole body scanning. Multi-modality imaging is an interesting area of research that aims at acquiring united morphological-functional image information for accurate diagnosing and staging of the disease. However, PET/CT procedure accompanied with high radiation dose from CT and administered radioactivity. The aim of the present study was to estimate the patients’ dose from ¹⁸F-fluorodeoxyglucose imaging (18F-FDG) hybrid PET/CT whole body scan.Materials and methodsRADAR (Radiation Dose Assessment Resource) software was used to estimate the effective dose for 156 patients (110 (70.5%)) males and 46 (39.5%) female) examined using Discovery PET/CT 710, GE Medical Systems installed at Kuwait Cancer Control Center (KCCC).ResultsThe effective dose results presented in this PET/CT study ranged from (1.56–9.94 mSv). The effective dose was calculated to be 3.88 mSv in females and 3.71 mSv in males. The overall breast (female), lung, liver, kidney and thyroid were 7.4, 7.2, 5.2, 4, 3 and 2.9, respectively.For females, the body mass index (BMI) was 28.49 kg/m² and for males it was 26.50 kg/m² which showed overweight values for both genders. Conclusions: The findings indicate that the effective dose of 18F-FDG in both male and female patients was not substantially different. The study suggested that the risk–benefit proportions of any ¹⁸F-FDG whole body PET/CT scan should be clarified and carefully weighed. Patient’s doses are lower compared with previous studies.     

The use of PET/CT in radiotherapy of patients with non-small cell lung cancer

The goal of this paper was to investigate the influence of FDG-PET/CT scan on the modification of staging and irradiation planning in patients suffering from non-small cell lung cancer (NSCLC). Fifteen patients suffering from NSCLC were analyzed by the authors from January, 2008 to July, 2009. The aim of the analysis was to examine the influence of FDG-PET/CT on irradiation planning and on decision-making of the complex oncologic therapy. The FDG-PET/CT scan was carried out in the position of irradiation performed later. For irradiation planning, planning target volumes (PTV) and the organs of risk were contoured on the patients' topometric CT slides as well as on the fused FDG-PET/CT slides. We evaluated how the application of PET/CT modified the stage of the illness, the complex oncologic therapeutic plan, the volume and the localization of the PTV, and the irradiation doses of the organs at risk. The mean and maximum dose of the spinal cord, the mean and V20 dose load of the lungs and the mean dose loads of the heart as well as of the left ventricle were measured. In 8 of 15 cases the stage of the disease and the treatment strategy was modified, since distant metastases were detected by the PET/CT. We evaluated the modification of the PTV and dose load of the organs at risk in 7 cases. According to the PET/CT the PTV was reduced in 5 cases (mean: 393.6 cm3) and was increased in 2 cases (mean: 250.8 cm3). Concerning the risk organs we found that the average (8.8 Gy/9.5 Gy) and maximum (33.4 Gy/36.4 Gy) dose load of the spinal cord increased, while the average (24.5 Gy/13.8 Gy) and V20 (33.7%/22.1%) dose load of the lungs decreased. We likewise found a decrease in the mean dose load of the heart (17.3 Gy/16.8 Gy) and left ventricle (12.9 Gy/9.6 Gy). In the majority of the cases the FDG-PET/CT scan modified the therapeutic decision, the size of the irradiated volume, and the dose load of the lung, the organ at risk causing the most difficulties at irradiation planning, was also reduced. The PET/CT scan plays an essential role in the complex oncologic treatment and irradiation therapy of NSCLC.     

Decreased levels of serum platelet-activating factor acetylhydrolase in patients with rheumatic diseases

PAF is a potent inflammatory compound known to stimulate the release of various cytokines involved in rheumatic diseases. Elevated blood PAF levels are reported in these patients. We report that serum PAF acetylhydrolase activity (AHA) levels are decreased in patients with rheumatoid arthritis or osteoarthritis as compared to healthy controls. Serum and synovial fluid AHA levels were correlated in these patients. The present study suggests the potential role of AHA in controling systemic and/or local PAF levels in patients with rheumatic diseases.     

Contents of antibodies to Bordetella pertussis antigens in patients with rheumatic diseases

Study of presence of antibodies against pertussis in 72 rheumatic patients (with uvenile rheumatoid arthritis, systemic lupus erythematosus, etc.) aged 1-18 year old without history of pertussis was performed. Mean age of the patients was 10.6 +/- 0.48 year old, duration of illness--51.2 +/- 4.42 months. Immunosupressive therapy at the time of the study was conducted in 68 (94.4%) children. Using ELISA method, IgG to pertussis toxin (PT) and to antigens of acellular pertussis vaccine (aPV) were detected in 98.6% and 100% of children. High titers of antibodies were detected more frequently in 7-18 year old age group, which can indicate recent pertussis disease or infection. Vaccination history was studied in 131 children with rheumatic diseases. Incidence of pertussis in 43 unvaccinated children was 116.3 per 1000, and in 16 children with incomplete vaccination--62.5 per 1000. Out of 75 patients, who received vaccination series and revaccination, clinically distinct pertussis was not diagnosed.     

Radiation dosimetry of 18F-flurocholine PET/CT studies in prostate cancer patients

PurposeWe aimed to evaluate the Equivalent Doses (H_Ts) to highly exposed organs as well as the Effective Dose (ED) for ¹⁸F-fluorocholine PET/CT scan in the follow-up of prostate cancer patients.MethodsFifty patients were administered with ¹⁸F-fluorocholine. The activities in organs with the highest uptake were derived by region-of-interest (ROI) analysis. OLINDA/EXM1.0 and Impact software were used to assess ED for the administered ¹⁸F-fluorocholine and CT scan, respectively, and the ¹⁸F-fluorocholine and CT-scan EDs summed to yield the total ED for the PET/CT procedure.ResultsThe calculated ¹⁸F-fluorocholine and CT scans EDs based on ICRP Publication 103 were 5.2 mSv/300 MBq and 6.7 mSv, respectively. The ¹⁸F-fluorocholine H_Ts to the liver, kidneys, spleen and pancreas were about threefold higher than those from the CT, which contributed a greater proportion of the total ED than the ¹⁸F-fluorocholine did.ConclusionsFor ¹⁸F-fluorocholine PET/CT procedures, about 40% of the ED is contributed by administered ¹⁸F-fluorocholine and 60% by the CT scan. The kidneys and liver were the highly exposed organs. Considering the large number of diagnostic procedures oncology patients undergo, radiation dosimetry is important in relation to the stochastic risk of such procedures.     

New perspectives of PET/CT in oncology

The fusion of PET and computed tomography, which provide metabolic and structural images, respectively, has improved the diagnostic precision of PET in oncology. Some current procedures in the PET/CT acquisition as contrast enhanced CT/PET, the use of PET/CT in radiotherapy planning and the PET-MRI can drastically change the approach of oncologic patients. Finally, inclusions of PET/CT in oncologic diagnostic algorithm and prognostic nomograms are pending issues.     

Cytokines in rheumatic diseases

IL-1 and related cytokines have multiple biologic activities relevant to the rheumatic diseases. In addition to mediating inflammatory and immune responses, these proteins regulate many aspects of connective tissue metabolism. The cytokines interact in complex cascades: because of this, and various technical reasons, the exact role of cytokines in the pathogenesis of rheumatic diseases remains uncertain. However, considerable experimental data suggest that the abnormal regulation of cytokines contributes to such siseases as inflammatory arthritis, systemic lupus erythematosus, scleroderma, and dermatomyositis. Animal models of these diseases have contributed to understanding the role of cytokines in pathogenesis. Furthermore, drugs useful in treating these diseases affect cytokine pathways; some cytokines, their antagonists, or related substances have been used therapeutically to treat rheumatic diseases. The therapeutic use of these agents will likely increase as knowledge about the role of cytokines in the pathogenesis of rheumatic diseases expands.Abbreviations CSF colony stimulating factor - ELAM endothelial leukocyte adherence molecule - FGF fibroblast growth factor - ICAM intercellular adhesion molecule - IFN interferon - IL interleukin - LFA lymphocyte function-associated antigen - LIF leukemia inhibitory factor - MCAF monocyte chemotactic/activitating factor - MCP monocyte chemoattractant protein - MDP muramyl dipeptide - PAI plasminogen activator inhibitor - PBMC peripheral blood mononuclear cells - PDGF platelet derived growth factor - PG prostaglandin - PHA phytohemagglutinin - Ra receptor antagonist - SLE systemic lupus erythematosus - SSc systemic sclerosis - TGF transforming growth factor - TNF tumor necrosis factor     

Osteoimmunology in rheumatic diseases

This review summarizes the recent advances of osteoimmunology, a new research field that investigates the interaction of the immune system with the skeleton. Osteoimmunology has contributed significantly to the understanding of joint destruction in rheumatoid arthritis and other forms of arthropathies. In particular, the molecular regulation of osteoclast formation and its control by proinflammatory cytokines have helped investigators to understand the mechanisms of bone erosion in rheumatic diseases. Osteoimmunology has also allowed an improvement in our knowledge of the structure-sparing effects of antirheumatic drug therapy. Moreover, recent advances in the understanding of the molecular regulation of osteophyte formation are based on the characterization of the regulation of bone formation by inflammation. This review highlights the key insights into the regulation of bone destruction and formation in arthritis. Moreover, concepts of how bone influences the immune system are discussed.     

Evaluation of 18F-PSMA-1007 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy

PurposeProstate-specific membrane antigen (PSMA) ligands targeting has shown promising results in staging of prostate cancer (PCa). The aim of present study was to evaluate the value of ¹⁸F-PSMA-1007 PET/CT in PCa patients with biochemical recurrence.Methods71 patients with PCa after radical prostatectomy (RP) were included in the present study. Median prostate-specific antigen (PSA) level was 1.27 ng/mL (range 0.01–67.40 ng/mL, n = 69). All patients underwent whole-body PET/CT imaging after injection of 333±38 MBq ¹⁸F-PSMA-1007. The distribution of PSMA-positive lesions was assessed. The influence of PSA level, androgen deprivation therapy and primary Gleason score on PSMA-positive finding and uptake of ¹⁸F-PSMA-1007 were evaluated.Results56 (79%) patients showed at least one pathological finding on ¹⁸F-PSMA-1007 PET/CT. The rates of positive scans were 50%, 80%, 100%, 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL, respectively. The median Gleason score was 8 (range 7–10), and higher Gleason score (≤7 vs. ≥8) leads to higher detection rates (58.3% (14/24) vs. 88.9% (32/36), P = 0.006). The median SUVmax of positive findings in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL were 4.51, 4.27, 11.50 and 14.08, respectively. The median SUVmax in patients with PSA level >2.0 ng/mL was significantly higher than that in patients with PSA ≤2.0 ng/mL (14.08 vs. 6.13, P<0.001).Conclusion¹⁸F-PSMA-1007 PET/CT demonstrated a high detection rate for patients with a raised PSA level after radical prostatectomy even in patients with extremely low PSA level (eg. PSA level ≤0.5 ng/mL), which was essential for further clinical management for PCa patients.