Visual and semiquantitative assessment of cranial artery inflammation with FDG-PET/CT in giant cell arteritis

BACKGROUND AND AIM: Assessing cranial artery inflammation plays an important role in the diagnosis of cranial giant cell arteritis (C-GCA). However, current diagnostic tests are limited. The use of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging is an established tool for assessing large vessel inflammation but is currently not used for assessment of the cranial arteries. This study aimed to evaluate the accuracy of FDG-PET/CT in the diagnosis of biopsy proven C-GCA and its relation to clinical presentation. METHODS: This retrospective case control study included temporal artery biopsy (TAB) positive C-GCA patients and age- and sex-matched controls. FDG-PET/CT scans were performed according to EANM/EARL guidelines, visually assessed by an experienced nuclear medicine physician, and semiquantitatively assessed using the maximum standardised uptake value (SUVmax). The visual and semiquantitative assessments were performed on the temporal arteries, maxillary arteries, vertebral arteries, and occipital arteries. Clinical signs and symptoms were scored for comparison. RESULTS: A total of 24 C-GCA patients and 24 controls were included in the study. Visual analysis revealed an 83% sensitivity and a 75% specificity. Receiver operating characteristic (ROC) analysis of the semiquantitative assessment revealed a 79% sensitivity and a 92% specificity when measuring SUVmax in the cranial arteries. Visual and semiquantitative assessments showed moderate agreement (Fleiss kappa 0.55). There was a positive correlation between the number of cranial symptoms and the SUVmax in the vertebral artery. CONCLUSION: FDG-PET/CT can reliably diagnose C-GCA by assessing cranial artery inflammation using SUVmax. Extending the use of FDG-PET/CT to include assessment of the cranial arteries may improve its diagnostic value in GCA and provide a suitable alternative to TAB. Moderate agreement between visual and semiquantitative assessment methods suggest diagnostic accuracy may be improved by further standardisation

Kinetics and 28-day test-retest repeatability and reproducibility of [C-11]UCB-J PET brain imaging

[C-11]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test-retest repeatability (TRT) of quantitative [C-11]UCB-J brain positron emission tomography (PET) imaging in Alzheimer's disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [C-11]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K-1) and volume of distribution (V-T) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_V-B and 2T4k_V-B described the [C-11]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for V-T, DVR and SRTM BPND were -2.2% +/- 8.5, 0.4% +/- 12.0 and -8.0% +/- 10.2, averaged over all subjects. [C-11]UCB-J kinetics can be well described by a 1T2k_V-B model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for V-T, DVR and BPND wa

N-(4-18F-Fluorobenzoyl)interleukin-2 for PET of human-activated T lymphocytes

Interleukin-2 (IL2) binds with high affinity to the IL2 receptors overexpressed on activated T lymphocytes in various pathologic conditions. Radiolabeling of IL2 with a positron-emitting isotope could provide a tool for noninvasive PET of activated T cells in immune-mediated diseases. We report the labeling of IL2 with N-succinimidyl 4-F-18-fluorolbenzoate (F-18-SFB) for the synthesis of N-(4-F-18-fluorobenzoyl)interleukin-2 (F-18-FB-IL2) and the in vitro and in vivo evaluation of this novel radiopharmaceutical for the detection of IL2 receptor-positive cells by PET. Methods: F-18-SFB was efficiently prepared using a 3-step radiochemical pathway. Purified F-18-SFB was incubated with IL2 in borate buffer (pH 8.5) and ethanol at 50 degrees C for 10 min. F-18-FB-IL2 was purified by reversed-phase high-performance liquid chromatography. As in vitro quality controls, a biologic binding assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis, mass spectrometry, and 3-chloroacetic acid precipitation stability tests were performed. Biodistribution studies were performed in BALB/c mice to evaluate the distribution of the tracer in healthy animals. PET experiments were performed in severe combined immunodeficiency disease mice inoculated with phytohemoagglutinin-activated human peripheral blood mononuclear cells (hPBMc). Whole-body images were acquired 30 min after injection of 5-15 MBq of F-18-FB-IL2. Results: F-18-SFB was produced with a 34%-38% radiochemical yield. The radiochemical purity after solid-phase extraction purification ranged from 93% to 96%. Conjugation of F-18-SFB to IL2 yielded F-18-FB-IL2 as the major product. The radiochemical yield of F-18-FB-IL2 after high-performance liquid chromatography purification was 25%-35% based on F-18-SFB. F-18-FB-IL2 was stable in plasma at 37 degrees C and capable of stimulating T cells to an extent similar to native IL2. A biodistribution study showed highest tracer uptake in the kidneys and bladder due to rapid renal clearance of the tracer. Small-animal PET images showed binding of F-18-FB-IL2 to activated hPBMc proportional to the number of injected cells. Conclusion: We report the successful labeling of IL2 with F-18 for PET of activated T lymphocytes. F-18-FB-IL2 is stable, is biologically active, and allows in vivo detection of activated T lymphocytes

Clinical use of differential nuclear medicine modalities in patients with ATTR amyloidosis

Histological proof remains the gold standard for the diagnosis of amyloidosis. Nuclear medicine imaging techniques are able to determine the amyloid load in the body. Currently, the best imaging modality is I-123-SAP scintigraphy. This modality has high sensitivity for detecting amyloid deposits in all amyloid subtypes. Involvement of liver and spleen can be visualized before clinical signs are present. The addition of single photon emission computed tomography improves the differentiation of overlying organs. However, I-123-SAP is not FDA approved. Its availability is limited to two centres in Europe. Furthermore, it is not suitable for imaging cardiac involvement of amyloidosis, due to movement, blood-pool content and lack of fenestrated endothelial in the myocardium. Phosphate derivates labelled with Tc-99m, are able to detect calcium compounds in cardiac amyloidosis. Finally, I-123-MIBG, an analogue of norepinephrine, can detect cardiac sympathetic innervation abnormalities as a consequence of amyloid deposits. Both these last techniques seem to be able to detect cardiac involvement before echocardiographic parameters are present. We illustrate the clinical use of these modalities with two patients with ATTR type amyloidosis

Nuclear Medicine Imaging in Concussive Head Injuries in Sports

Concussions in sports and during recreational activities are a major source of traumatic brain injury in our society. This is mainly relevant in adolescence and young adulthood, where the annual rate of diagnosed concussions is increasing from year to year. Contact sports (e.g., ice hockey, American football, or boxing) are especially exposed to repeated concussions. While most of the athletes recover fully from the trauma, some experience a variety of symptoms including headache, fatigue, dizziness, anxiety, abnormal balance and postural instability, impaired memory, or other cognitive deficits. Moreover, there is growing evidence regarding clinical and neuropathological consequences of repetitive concussions, which are also linked to an increased risk for depression and Alzheimer’s disease or the development of chronic traumatic encephalopathy. With little contribution of conventional structural imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) to the evaluation of concussion, nuclear imaging techniques (i.e., positron emission tomography (PET) and single-photon emission computed tomography (SPECT)) are in a favorable position to provide reliable tools for a better understanding of the pathophysiology and the clinical evaluation of athletes suffering a concussion

123I-Labelled metaiodobenzylguanidine for the evaluation of cardiac sympathetic denervation in early stage amyloidosis

Cardiac amyloidosis is a rare disorder, but it may lead to potentially life-threatening restrictive cardiomyopathy. Cardiac manifestations frequently occur in primary amyloidosis (AL) and familial amyloidosis (ATTR), but are uncommon in secondary amyloidosis (AA). Echocardiography is the method of choice for assessing cardiac amyloidosis. Amyloid deposits impair the function of sympathetic nerve endings. Disturbance of myocardial sympathetic innervations may play an important role in the remodelling process. I-123-MIBG can detect these innervation changes. Patients with biopsy-proven amyloidosis underwent general work-up, echocardiography and I-123-MIBG scintigraphy. Left ventricular internal dimensions and wall thickness were measured, and highly refractile cardiac echoes (sparkling) were analysed. Early (15 min) and late (4 h) heart-to-mediastinum ratio (HMR) and wash-out rate were determined after administration of MIBG. Included in the study were 61 patients (30 women and 31 men; mean age 62 years; 39 AL, 11 AA, 11 ATTR). Echocardiographic parameters were not significantly different between the groups. Sparkling was present in 72 % of ATTR patients, in 54 % of AL patients and in 45 % of AA patients. Mean late HMR in all patients was 2.3 +/- 0.75, and the mean wash-out rate was 8.6 +/- 14 % (the latter not significantly different between the patient groups). Late HMR was significantly lower in patients with echocardiographic signs of amyloidosis than in patients without (2.0 +/- 0.70 versus 2.8 +/- 0.58, p < 0.001). Wash-out rates were significantly higher in these patients (-3.3 +/- 9.9 % vs. 17 +/- 10 %, p < 0.001). In ATTR patients without echocardiographic signs of amyloidosis, HMR was lower than in patients with the other types (2.0 +/- 0.59 vs. 2.9 +/- 0.50, p = 0.007). MIBG HMR is lower and wash-out rate is higher in patients with echocardiographic signs of amyloidosis. Also, I-123-MIBG scintigraphy can detect cardiac denervation in ATTR patients before signs of amyloidosis are evident on echocardiography

Development and testing of a new disposable sterile device for labelling white blood cells

Aim. White blood cell (WBC) labelling requires isolation of cells from patient's blood under sterile conditions using sterile materials, buffers and disposables under good manufacturing practice (GMP) conditions. Till now, this limited the use of white blood cell scintigraphy (WBC-S) only to well equipped laboratories with trained personnel. We invented, developed and tested a disposable, sterile, closed device for blood manipulation, WBC purification and radionuclide labelling without exposing patient's blood and the operator to contamination risks. This device prototype and a final industrialized device (Leukokit (R)) were tested for WBC labelling and compared to standard procedure. Leukokit (R) was also tested in an international multi-centre study for easiness of WBC purification and labelling. Methods. On the device prototype we tested in parallel, with blood samples from 7 volunteers, the labelling procedure compared to the standard procedure of the International Society of Radio labeled Blood Elements (ISORBE) consensus protocol with respect to cell recovery, labelling efficiency (LE), cell viability (Trypan Blue test) and sterility (haemoculture). On the final Leukokit (R) we tested the biocompatibifity of all components, and again the LE, erythro-sedimentation rate, cell viability, sterility and apyrogenicity. ACD-A, HES and PBS provided by Leukokit (R) were also compared to Heparin, Dextran and autologous plasma, respectively. In 4 samples, we tested the chemotactic activity of purified WBC against 1 mg/ml of lipopolysaccharide (LPS) and chemotaxis of Tc-99m-HMPAO-labelled WBC (925 MBq) was compared to that of unlabelled cells. For the multi-centre study, 70 labellings were performed with the Leukokit by 9 expert operators and 3 beginners from five centers using blood from both patients and volunteers. Finally, Media-Fill tests were performed by 3 operators on two different days (11 procedures) by replacing blood and kit reagents with bacterial culture media (Tryptic Soy Broth) and testing sterility of aliquots of the medium at the end of procedure. Results. Tests performed with the prototype showed no significant differences with the standard procedure but a faster and safer approach. Tests performed with the final Leukokit (R) confirmed full biocompatibility, sterility and apyrogenicity of all reagents and plastic ware. Average WBC recovery with Leukokit (R) was comparable to that of the ISORBE protocol (117x10(6)+/- 24x10(6) vs. 132x10(6)+/- 29x10(6) cells, P=not significant). No differences in red blood cells and platelet content were observed. LE was 82% +/- 3% for Leukokit (R) and 65 +/- 5% for control (P=0.0003) being PBS vs autologous plasma the main reason of such difference. Cell viability was always >99.9% in both conditions. Chemotactic tests showed no differences between all Leukokit samples and controls. Haemocultures and Media-Fill tests were always sterile. The procedure was well accepted by expert operators and beginners, with a very fast learning curve (confidence after 2 +/- 2 labellings). Conclusion. The invented device offers high level of protection to operators and patients. The derived Leukokit (R) is safe and easy to use, and gives a high LE of WBC without affecting cell viability and function. Being a registered closed, sterile medical device, it may allow easier and faster WBC labelling that is not limited to only well equipped laboratories. Also simultaneously labelling of multiple patients is possible

Adverse cardiovascular effects of anabolic steroids: pathophysiology imaging

Background : Anabolic-androgenic steroids (AAS) are widely abused for enhancing muscle mass, strength, growth and improving athletic performance. Materials and methods : In recent years, many observational and interventional studies have shown important adverse cardiovascular effects of AAS abuse. Conclusions : This review discusses established and future perspectives of novel molecular imaging techniques that may serve as potential tools for early detection of AAS-associated cardiovascular disorders

The Role of Imaging Techniques to Define a Peri-Prosthetic Hip and Knee Joint Infection: Multidisciplinary Consensus Statements

Diagnosing a peri-prosthetic joint infection (PJI) remains challenging despite the availability of a variety of clinical signs, serum and synovial markers, imaging techniques, microbiological and histological findings. Moreover, the one and only true definition of PJI does not exist, which is reflected by the existence of at least six different definitions by independent societies. These definitions are composed of major and minor criteria for defining a PJI, but most of them do not include imaging techniques. This paper highlights the pros and cons of available imaging techniques-X-ray, ultrasound, computed tomography (CT), Magnetic Resonance Imaging (MRI), bone scintigraphy, white blood cell scintigraphy (WBC), anti-granulocyte scintigraphy, and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), discusses the added value of hybrid camera systems-single photon emission tomography/computed tomography (SPECT/CT), PET/CT and PET/MRI and reports consensus answers on important clinical questions that were discussed during the Third European Congress on Inflammation/Infection Imaging in Rome, December 2019.status: publishe

In vivo and in vitro evidence that ⁹⁹mTc-HYNIC-interleukin-2 is able to detect T lymphocytes in vulnerable atherosclerotic plaques of the carotid artery

Recent advances in basic science have established that inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Inflammatory cells are thought to be responsible for the transformation of a stable plaque into a vulnerable one. Lymphocytes constitute at least 20 % of infiltrating cells in these vulnerable plaques. Therefore, the interleukin-2 (IL-2) receptor, being overexpressed on activated T lymphocytes, may represent an attractive biomarker for plaque vulnerability. The aim of this study was to evaluate the specificity of radiolabelled IL-2 [(99m)Tc-hydrazinonicotinamide (HYNIC)-IL-2] for imaging the lymphocytic infiltration in carotid plaques in vivo by planar and single photon emission computed tomography (SPECT)/CT imaging and ex vivo by microSPECT and autoradiography.status: publishe