Interleukin-18 as a mediator of systemic juvenile idiopathic arthritis

The objective of this report is to explore the balance between serum and synovial fluid levels of interleukin (IL)-18 in children with juvenile idiopathic arthritis (JIA). Blood samples were obtained from 81 children with JIA and 18 control children. Synovial fluid samples were collected from 16 children with oligoarticular JIA. Concentrations of IL-18 were determined using commercial kit. Patients with systemic JIA had higher serum levels of IL-18 than patients with other forms of JIA or control children, both during the active (median, range: 6,240, 1,600–78,750 pg/ml) and inactive (1,615, 513–3,270 pg/ml) phase of disease [analysis of variance (ANOVA), P < 0.05). Levels of IL-18 in sera of children with oligoarticular JIA (255, 89–4,342 pg/ml) were similar to the respective synovial fluid levels (217, 89–1,245 pg/ml). Serum levels of IL-18 were proportional to the erythrocyte sedimentation rate and levels of C-reactive protein, but inversely proportional to the haemoglobin levels. IL-18 appears to be an important mediator of systemic JIA, while it seems of a lesser relevance in pathogenesis of other JIA forms. Therefore, inhibition of IL-18 might be a base for a successful biological therapy for systemic JIA.     

'Prefrontal' cognitive performance of healthy subjects positively correlates with cerebral FDOPA influx: an exploratory [18F]-fluoro-L-DOPA-PET investigation

Dopamine neurotransmission influences those cognitive processes, which are generally regarded as prefrontal cortical functions. In previous positron-emission-tomography (PET) studies, net blood-brain clearance of [18F]-fluoro-l-DOPA (FDOPA) correlated with impaired cognitive performance in patients with Parkinson's disease or schizophrenia. We hypothesized that FDOPA influx also correlates with performance of cognitive tasks associated with prefrontal functioning in healthy volunteers. The net blood-brain clearance of FDOPA (K(in)(app)) was mapped in a group of 11 healthy volunteers and calculated in striatal volumes-of-interest. The Wisconsin-Card-Sorting-Test (WCST), Stroop-Test, Trail-Making-Test (TMT-A/B), and Continuous-Performance-Test (CPT-M) had been administered previously to the same subjects. No correlation of K(in) (app) with perseverative errors in WCST or age could be found. However, there were significant positive correlations between the magnitude of K(in)(app) in caudate nucleus, putamen, and midbrain with performance of the TMT-B, CPT-M, and the Stroop test. Highest correlations were found between the time needed to perform the Stroop interference task and the K(in)(app) of striatal areas (Caudate nucleus: -0.780, P = 0.005; putamen: -0.870, P < 0. 001). Thus, the present findings reveal a strong correlation between dopamine synthesis capacity in striatum of healthy volunteers and performance of cognitive tasks linked to the prefrontal cortex.     

Post transplant lymphoproliferative disease in pediatric solid organ transplant patients: a possible role for [18F]-FDG-PET(/CT) in initial staging and therapy monitoring

Post transplant lymphoproliferative disease (PTLD) is a severe complication after solid organ or bone marrow transplantation. In pediatric transplant recipients PTLD is the most common malignancy. The aim of this study was to evaluate a possible role for positron emission tomography with [18F]-2-fluoro-2-desoxy-glucose (FDG) in the initial staging and in therapy monitoring of pediatric patients suffering from biopsy-proven CD20-positive PTLD after solid organ transplantation. Seven pediatric patients were included. All available imaging studies - CT (n=15), MRI (n=16) and PET/PETCT (n=16) - were reviewed on a lesion by lesion base. The performance of FDG-PET in the initial staging and during therapy with a chimeric anti-CD20 antibody was compared to conventional cross sectional imaging and correlated with the clinical outcome. FDG-PET identified all sites of disease as shown by CT/MRI and helped to clarify the significance of equivocal findings. The initial stage of disease was correctly identified by FDG-PET alone when compared to CT/MRI. During therapy, FDG-PET was superior to conventional cross-sectional imaging in the early evaluation of response.     

Breast MRI and<Superscript>18</Superscript>F FDG PET/CT in the management of breast cancer

GOALS: 18F FDG PET/CT is used for diagnosis, staging and establishing the response to therapy in various malignancies, including breast cancer (BC). Dedicated breast MRI (BMRI) is gaining a role in the management of BC patients (pts), demonstrating high sensitivity and specificity for detection of small lesions. We were therefore prompted to review our experience with PET and BMRI in BC. METHODS: This is a retrospective study of 21 women with BC, 30-76 years old, who had BMRI and whole-body FDG PET/CT at our institution from Jun 2002 to May 2005. A total of 6 patients (group A) had BMRI and PET/CT in the preoperative period and 15 patients (group B) had BMRI and PET/CT after surgery. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed. RESULTS: For group A, BMRI identified breast lesions in 4 patients, while PET/CT was able to identify breast lesions in 5 patients. All these were proven to be malignancy on pathology examination. In group B, BMRI detected recurrent breast lesions in 8 patients, with 88.9% sensitivity and 83.3% specificity. In the same patient population, PET/CT was 33.3% sensitive and 91.7% specific. As a whole body examination, PET/CT revealed metastatic disease in 6 patients (100% sensitive and 90% specific). Overall, sensitivities and specificities for breast disease detection were 85.7% and 85.7% for BMRI, and 75% and 92.3% for 18F FDG PET/ CT. CONCLUSIONS: As expected, BMRI is more sensitive than PET/CT in the detection of breast lesions. However, PET/CT as a whole-body examination changed the management of disease by detection of distant lesions in 6 of the 21 patients. Our study suggests that 18F FDG PET/CT and BMRI should be considered as complimentary imaging tools in the pre- and postoperative work-up of patients diagnosed with breast cancer.     

Normal uptake of <Superscript>18</Superscript>F-FDG in the testis: an assessment by PET/CT

Objective The aim of this study was to assess the physiological uptake of ¹⁸F-fluoro-2-deoxyglucose (FDG) by an apparently normal testis with combined positron emission tomography–computed tomography (PET/CT) and its correlation with age, blood glucose level, and testicular volume. Methods The testicular uptake of ¹⁸F-FDG, expressed as the standardized uptake value (SUV), was measured on PET/CT images in 203 men. The correlation between SUV and age, blood glucose level, and testicular volume was assessed. Results The SUV in the total of 406 testes was 2.44 ± 0.45 (range 1.23–3.85). The SUV was 2.81 ± 0.43 (2.28–3.85) for 30–39 years (n = 12), 2.63 ± 0.45 (1.77–3.75) for 40–49 years (n = 64), 2.46 ± 0.35 (1.44–3.15) for 50–59 years (n = 82), 2.51 ± 0.41 (1.50–3.46) for 60–69 years (n = 86), 2.43 ± 0.47 (1.42–3.29) for 70–79 years (n = 86), and 2.18 ± 0.45 (1.23–3.03) for 80–89 years (n = 76). When we calculated the mean SUV of bilateral testes in each patient, there were significant statistical differences between those in the age group of 30–39 years and 80–89 years, 40–49 years and 80–89 years, and 50–60 years and 80–89 years, when using an unpaired test with Bonferroni correction. The laterality index (|L − R|/(L + R) × 2) in 203 men was 0.066 ± 0.067 (0–0.522). There was a mild correlation between the mean SUV and age (r = −0.284, P < 0.001) as well as between the mean SUV and mean volume (r = +0.368, P < 0.001). There was no correlation between the mean SUV and glucose blood level (r = −0.065, P = 0.358). Conclusions Some uptake of FDG is observed in the normal testis and declines slightly with age. Physiological FDG uptake in the testis should not be confused with pathological accumulation.     

Nonionic intravenous contrast agent does not cause clinically significant artifacts to <Superscript>18</Superscript>F-FDG PET/CT in patients with lung cancer

Objective This study was performed to evaluate the effects of intravenous (i.v.) contrast agent on semi-quantitative values and lymph node (LN) staging of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with lung cancer. Methods Thirty-five patients with lung cancer were prospectively included. Whole-body PET and nonenhanced CT images were acquired 60 min following the i.v. injection of 370 MBq ¹⁸F-FDG and subsequently, enhanced-CT images were acquired with the i.v. administration of 400 mg iodinated contrast agent without positional change. PET images were reconstructed with both nonenhanced and enhanced CTs, and the maximum and average standardized uptake values (SUV_max and SUV_ave) calculated from lung masses, LNs, metastatic lesions, and normal structures were compared. To evaluate the effects of the i.v. contrast agent on LN staging, we compared the LN status on the basis of SUVs (cut-offs; SUV_max = 3.5, SUV_ave = 3.0). Results The mean differences of SUV_max in normal structures between enhanced and nonenhanced PET/CT were 15.23% ± 13.19% for contralateral lung, 8.53% ± 6.11% for aorta, 5.85% ± 4.99% for liver, 5.47% ± 6.81% for muscle, and 2.81% ± 3.05% for bone marrow, and those of SUV_ave were 10.17% ± 9.00%, 10.51% ± 7.89%, 4.95% ± 3.89%, 5.66% ± 9.12%, and 2.49% ± 2.50%, respectively. The mean differences of SUV_max between enhanced and nonenhanced PET/CT were 5.89% ± 3.92% for lung lesions (n = 41), 6.27% ± 3.79% for LNs (n = 76), and 3.55% ± 3.38% for metastatic lesions (n = 35), and those of SUV_ave were 3.22% ± 3.01%, 2.86% ± 1.71%, and 2.33% ± 3.95%, respectively. Although one LN status changed from benign to malignant because of contrast-related artifact, there was no up- or down-staging in any of the patients after contrast enhancement. Conclusions An i.v. contrast agent may be used in PET/CT without producing any clinically significant artifact.     

F-18 FDG PET/CT imaging of low-grade mucoepidermoid carcinoma of the bronchus

Mucoepidermoid carcinomas in the bronchial tree are extremely rare tumors. Such tumors are classified into low-grade and high-grade on the basis of histological criteria. Fluorine-18-fluorodeoxyglucose positron emission tomography (F-18 FDG PET) is a useful technique for the evaluation of pulmonary lesions; however, to our knowledge, F-18 FDG PET findings in mucoepidermoid carcinoma of the bronchus have been described in only a few cases. Identifiable focal F-18 FDG uptake has been reported in high-grade mucoepidermoid carcinoma, but it is unclear whether F-18 FDG accumulates in low-grade mucoepidermoid carcinoma. Here, we present the case of a 37-year-old woman, with pathologically proven low-grade mucoepidermoid carcinoma, who underwent high-resolution computed tomography (CT) and F-18 FDG PET/CT before treatment.     

A hybrid algorithm for PET/CT image merger in hybrid scanners

Purpose To improve the PET image quality of a hybrid PET/CT scanner by merging CT borders with PET texture. PET/CT scanners provide both high-resolution CT images showing anatomical details and PET images of low-resolution physiological information about radiopharmaceutical uptake. Standard smoothing of noisy PET images may further impair PET resolution, reducing small lesion detectability. Methods The CT edge data and the PET texture data were merged using a modified form of an algorithm called HCT (hybrid computed tomography). In merged PET/CT images, each PET pixel value was estimated by iteratively applying a corrected 2D Taylor expansion to each of its eight neighbors. The spatial derivative term was used only near anatomical edges provided by the CT. This counts-preserving algorithm was tested on a special resolution phantom and patient data sets obtained by PET/CT acquisitions. Results The HCT algorithm provided phantom PET images with sharp borders and improved resolution (≤3 mm as compared to ≥4 mm). HCT increased the signal to background contrast ratios by an average of 61% (40–89%) while maintaining noise reduction similar to the Gaussian filtering standard in PET. In the clinical PET images, HCT allowed for an improved delineation of pulmonary and pelvic lesions and an improved visualization of the brain. Conclusion A new reconstruction algorithm for merging CT anatomical edge data with functional PET data has been introduced. The algorithm smoothes noisy PET images while retaining sharper edges at corresponding anatomical borders, resulting in an improvement in resolution and contrast ratio.     

Characterization of membrane potential-dependent uptake of the novel PET tracer <Superscript>18</Superscript>F-fluorobenzyl triphenylphosphonium cation

Purpose Mitochondrial dysfunction has been attributed a critical role in the etiology and pathogenesis of numerous diseases, and is manifested by alterations of the organelle’s membrane potential (Δψ_m). This suggests that Δψ_m measurement can be highly useful for diagnostic purposes. In the current study, we characterized the capability of the novel PET agent ¹⁸F-fluorobenzyl triphenylphosphonium (¹⁸F-FBnTP) to assess Δψ_m, compared with the well-established voltage sensor ³H-tetraphenylphosphonium (³H-TPP). Methods ¹⁸F-FBnTP and ³H-TPP uptake under conditions known to alter Δψ_m and plasma membrane potential (Δψ_p) was assayed in the H345 lung carcinoma cell line. ¹⁸F-FBnTP biodistribution was assessed in CD1 mice using dynamic PET and ex vivo gamma well counting. Results ¹⁸F-FBnTP and ³H-TPP demonstrated similar uptake kinetics and plateau concentrations in H345 cells. Stepwise membrane depolarization resulted in a linear decrease in ¹⁸F-FBnTP cellular uptake, with a slope (−0.58±0.06) and correlation coefficient (0.94±0.07) similar (p>0.17) to those measured for ³H-TPP (−0.63±0.06 and 0.96±0.05, respectively). Selective collapse of Δψ_m caused a substantial decrease in cellular uptake for ¹⁸F-FBnTP (81.6±8.1%) and ³H-TPP (85.4±6.7%), compared with control. Exposure to the proapoptotic staurosporine, known to collapse Δψ_m, resulted in a decrease of 68.7±10.1% and 71.5±8.4% in ¹⁸F-FBnTP and ³H-TPP cellular uptake, respectively. ¹⁸F-FBnTP accumulated mainly in kidney, heart and liver. Conclusion ¹⁸F-FBnTP is a mitochondria-targeting PET radiopharmaceutical responsive to alterations in membrane potential with voltage-dependent performance similar to that of ³H-TPP. ¹⁸F-FBnTP is a promising new voltage sensor for detection of physiological and pathological processes associated with mitochondrial dysfunction, such as apoptosis, using PET.