Abstract
Aims
To explore the relationship between temperature measurements derived by microwave radiometry (MWR) and carotid flurodeoxyglucose (FDG) uptake and assess their association with ...histological and immunohistochemistry findings in patients with high-grade carotid stenosis.
Methods and results
In 21 patients undergoing carotid endarterectomy, carotid inflammation was evaluated by both FDG positron emission/computed tomography (FDG-PET/CT) imaging and MWR measurements. Carotid inflammation was assessed by PET/CT as target-to-background ratio (TBR) by obtaining measurements in consecutive axial slices 2 cm below to 2 cm above the carotid bifurcation. Temperature difference (ΔT) by MWR was assigned as the maximum–minimum temperature measurements over the corresponding carotid segments. The extent of lipid core, calcification as well as CD68 and CD31 levels were also assessed. There was a significant correlation between ΔT values and FDG uptake (R = 0.40, P = 0.01), but no correlation between the degree of angiographic stenosis and ΔT values (R = −0.02, P = 0.91) or PET/CT measurements (R = −0.28, P = 0.86). Patients with plaques containing high lipid core extension or low calcification exhibited higher ΔT (P = 0.001 and P < 0.001, respectively) and FDG uptake values (P = 0.02 and P = 0.02, respectively). Patients with plaques containing increased CD68 expression exhibited higher ΔT and FDG uptake measurements.
Conclusion
Carotid plaque inflammation was evaluated by temperature measurements, which were correlated with FDG-PET/CT indices, confirmed by histopathology and immunohistochemistry findings. Structural changes did not predict inflammatory process. The implications of these findings in risk stratification and management of patients with carotid atherosclerosis and the precise algorithm for potential clinical utilization of MWR and PET/CT remain to be determined.
The beneficial effects of checkpoint blockade in tumor immunotherapy are limited to patients with increased tumor-infiltrating lymphocytes (TILs). Delineation of the regulatory networks that ...orchestrate the presence of TILs holds great promise for the design of effective immunotherapies. Podoplanin/gp38 (PDPN)-expressing lymph node stromal cells (LNSCs) are present in tumor stroma; however, their effect in the regulation of TILs remains elusive. Herein we demonstrate that intratumor injection of ex-vivo-isolated PDPN
+
LNSCs into melanoma-bearing mice induces elimination of TILs and promotes tumor growth. In support, PDPN
+
LNSCs exert their function through direct inhibition of CD4
+
T cell proliferation in a cell-to-cell contact independent fashion. Mechanistically, we demonstrate that PDPN
+
LNSCs mediate T cell growth arrest and induction of apoptosis to activated CD69
+
CD4
+
T cells. Importantly, LTbR-Ig-mediated blockade of PDPN
+
LNSCs expansion and function significantly attenuates melanoma tumor growth and enhances the infiltration and proliferation of CD4
+
TILs. Overall, our findings decipher a novel role of PDPN-expressing LNSCs in the elimination of CD4
+
TILs and propose a new target for tumor immunotherapy.
The aim of this study was to develop a dual-modality positron emission tomography/magnetic resonance (PET/MR) imaging probe by radiolabeling gadolinium-containing AGuIX derivatives with the ...positron-emitter Gallium-68 (
Ga).
AGuIX@NODAGA nanoparticles were labeled with
Ga at high efficiency. Tumor accumulation in an appropriate disease model was assessed by ex vivo biodistribution and in vivo PET/MR imaging.
Ga-AGuIX@NODAGA was proven to passively accumulate in U87MG human glioblastoma tumor xenografts. Metabolite assessment in serum, urine and tumor samples showed that
Ga-AGuIX@NODAGA remains unmetabolized up to at least 60 min postinjection.
This study demonstrates that
Ga-AGuIX@NODAGA can be used as a dual-modality PET/MR imaging agent with passive accumulation in the diseased area, thus showing great potential for PET/MR image-guided radiation therapy.
Despite advances in the treatment of oncology patients, therapy-related side effects may lead to premature morbidity. Inflammatory activation that has been linked to cardiovascular disease is crucial ...for the pathogenesis of both Hodgkin (HL) and non-Hodgkin lymphoma (NHL).
The purpose of this study was to assess the vascular effects of chemotherapy in patients with HL and NHL by positron emission tomography/computed tomography with 18-fluorodeoxyglucose (18-FDG PET/CT) and to investigate interactions with systemic inflammation as assessed by circulating inflammatory markers.
Between July 2015 and July 2019, 65 consecutive patients (mean age 56 ± 17.78 years) with confirmed diagnosis of either HL (n = 33) or NHL (n = 32) were prospectively studied. PET/CT imaging was performed at baseline, at an interim phase, and after first-line treatment. Aortic FDG uptake was assessed by measuring global aortic target-to-background ratio (GLA-TBR). Serum biomarkers interleukin (IL)-6 and IL-1b were measured at each phase.
Patients with HL demonstrated significant reduction in aortic TBR after first-line treatment (median GLA-TBR baseline: 1.98, median GLA-TBR third scan: 1.75, median difference = −0.20, 95% CI: −0.07 to −0.33, P = 0.006), which remained significant after adjustment for confounders (adj. R2 of model = 0.53). In contrast, patients with NHL did not demonstrate a significant aortic inflammation response (P = 0.306). Furthermore, patients with HL demonstrated a significant reduction in IL-6 (P = 0.048) and IL-1b (P = 0.045), whereas patients with NHL did not demonstrate significant reduction in IL-6 (P = 0.085) and IL-1b levels (P = 0.476).
Aortic inflammation, as assessed by 18-FDG PET/CT, is reduced in HL patients after first-line treatment but not in NHL patients. These findings imply that different pathophysiological pathways and different therapies might affect the arterial bed in different ways for patients with lymphoma.
Display omitted
Purpose
In FDG PET/CT, standardized uptake value (SUV) is used to measure metabolic activity but detects un-phosphorylated FDG as well as phosphorylated FDG (FDG6P). Our aim was to determine the ...proportions of intrahepatic and intrasplenic FDG that are phosphorylated after FDG injection and compare them with SUVs.
Methods
Sixty patients undergoing whole-body PET/CT 60 min post-injection of FDG first had dynamic PET imaging for 30 min with measurement of hepatic and splenic FDG clearances using Patlak-Rutland analysis. The gradient of the Patlak-Rutland plot, which is proportional to clearance (Ki), was normalized to the intercept, which is proportional to FDG distribution volume (
V
(0)) with the same proportionality constant. Using measured values of Ki/
V
(0), FDG6P/FDG ratios as functions of time in the two organs were measured for assumed FDG blood disappearance half-times of 40, 50 and 60 min. Hepatic and splenic SUVs were measured from whole-body PET/CT.
Results
The mean (SD) Ki/
V
(0) was 0.0036 (0.0021) and 0.0060 (0.0041) ml/min/ml for the liver and spleen, respectively, but the hepatic SUV was 1.36-fold higher than the splenic SUV. This discrepancy was explained by the hepatic
V
(0) being 1.6-fold higher than the splenic
V
(0). The percentages of FDG phosphorylated 60 min post-injection were 27, 25 and 23% for the liver and 39, 36 and 34% for the spleen, for blood clearance half-times of 40, 50 and 60 min, respectively. SUV indices correlated poorly with Ki/
V
(0) for both organs.
Conclusions
SUV is largely determined by un-phosphorylated FDG in dynamic exchange with blood FDG, explaining the poor correlations between SUV indices and Ki/
V
(0).
Abstract Background: Commercially available bile-acid sequestrants are not well tolerated by >80% of patients. Objective: The aim of the present study was to assess the effectiveness and tolerability ...of colesevelam hydrochloride in patients who developed bile-acid malabsorption after cancer therapy. Methods: The present study comprised 2 parts: a retrospective chart review of the electronic patient records and a patient questionnaire assessing outcome measures. All patients included in this study had a diagnosis of cancer and were being followed up in a cancer clinic at The Royal Marsden Hospital. In addition, all had symptoms of bile-acid malabsorption for >3 months and had been prescribed colesevelam in the gastroenterology clinic at the hospital. The electronic records of patients who were prescribed colesevelam between 2004 and 2007 were obtained from the hospital pharmacy. Those patients who were prescribed colesevelam and did not take any of the prescribed medication or did not return for a follow-up clinical review were excluded. To help further assess outcomes, a questionnaire was mailed to patients who were still residing in the United Kingdom, were not terminally ill, and were not lost to follow-up. The questionnaire comprised questions that assessed medication history (ie, whether patients were still taking colesevelam or not and the reason for not taking colesevelam), dosage, effectiveness for symptom relief, and adverse events. Results: In total, 45 patients (37 women and 8 men; median age, 58 years range, 32–89 years) who received treatment with colesevelam between 2004 and 2007 were included. Of these, 36 were sent a questionnaire and 30 responded. Identifiable causes of bile acid malabsorption in this sample population were pelvic radiotherapy (n = 29), small-bowel resection (12), upper gastrointestinal surgery (2), high-dose chemotherapy (1), and new-onset Crohn's disease (1). Of these patients, 67% (30/45) had not previously responded to cholestyramine treatment, but following treatment with colesevelam, this group had a recorded improvement in: diarrhea, 83% (25/30); urgency of defecation, 74% (20/27); frequency of defecation, 72% (21/29); steatorrhea, 71% (12/17); abdominal pain, 68% (15/22); and fecal incontinence, 62% (13/21). Based on the medical chart review and the patient questionnaire, after colesevelam treatment, the following proportions of all 45 patients studied experienced improvement in symptoms: loose stool (diarrhea), 88% (medical chart) and 80% (questionnaire); frequency of defecation, 77% and 83%, respectively; steatorrhea, 76% and 80%; urgency of defecation, 76% and 80%; abdominal pain, 74% and 58%; and fecal incontinence, 69% and 74%. During the study period, 15 patients discontinued colesevelam: ineffectiveness, 5; adverse events, 5 (because ≥1 of the following: bloating, constipation, heartburn, abdominal pain, flatulence, or perianal soreness); and other reasons, 7 (too many tablets or tablets difficult to swallow 3; symptoms resolved 2; colesevelam replaced with another medication 1; and lost to follow-up 1). Sixty-seven percent (30/45) of patients continued using colesevelam for up to 4 years. Conclusion: In view of the data found in this retrospective chart review and patient questionnaire, prospective, double-blind, placebo-controlled trials of colesevelam for bile acid malabsorption are warranted.
Chemotherapy regimens for breast cancer treatment can promote vascular dysfunction and lead to high cardiovascular risk.
To investigate the cardiovascular burden and vascular inflammation in ...metastatic breast cancer patients receiving CDK 4/6 inhibitors or everolimus in addition to standard hormonal treatment.
22 consecutive female patients with metastatic breast cancer were enrolled. Relative wall thickness (RWT) and left ventricle mass (LVM) measurements by transthoracic echocardiography were obtained followed by 24-h ambulatory blood pressure monitoring, and
F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Uptake of the radiotracer in the aortic wall was estimated as tissue-to-background ratio (TBR). Each patient was assessed for the aforementioned parameters before the initiation and after 6 months of treatment.
At follow up, patients assigned to CDK 4/6 treatment demonstrated increased 24-h systolic blood pressure (SBP) (
= 0.004), daytime SBP (
= 0.004) and night time SBP (
= 0.012) (Group effect). The 24-h mean arterial pressure measurements were also higher in CDK 4/6 population, in comparison to everolimus that displayed firm values (Group effect-
= 0.035, Interaction effect-
= 0.023). Additionally, 24 h diastolic blood pressure recordings in CDK 4/6 therapy were higher opposed to everolimus that remained consistent (Interaction effect-
= 0.010). In CDK 4/6 group, TBR aorta also increased significantly, whereas TBR values in everolimus remained stable (Interaction effect-
= 0.049). Both therapeutic regimens displayed statistically significant damaging effect to RWT and LVM.
CDK 4/6 inhibitors and hormonal treatment can lead to increased vascular inflammation, and higher blood pressure compared to the combination of everolimus and hormonal treatment. Moreover, both treatment strategies promoted left ventricle remodeling.
To develop and test a model predicting 2-deoxy-2-
18
Ffluoro-
d
-glucose (
18
FFDG) standardized uptake value (SUV) changes over time in the aorta and the superior vena cava (SVC). Maximum aortic SUV ...and mean SVC SUV were determined at two time points (T1 and T2) in the ascending (ASC), descending (DSC), abdominal (ABD) aorta, aortic arch (ARC) and SVC of patients who have undergone
18
FFDG PET/CT for clinical purposes. For SUV prediction at T2, linear and non-linear models of SUV difference for a given time change were developed in a derivation group. The results were tested in an independent validation group, whilst model reproducibility was tested in patients of the validation group who have undergone a second clinically indicated scan. Applying the linear model in the derivation group, there were no statistically significant differences in measurements obtained in the examined segments: mean differences ranged from 0 ± 0.10 in SVC to 0.01 ± 0.13 in ARC between measured and predicted SUV. In contrast, in the non-linear model, there were statistically significant differences in measurements, except in ARC, with mean differences ranging from 0.04 ± 0.14 in ARC to 0.28 ± 0.13 in ABD. In the validation group using the linear model, there were no statistically significant differences, with mean differences ranging from − 0.01 ± 0.08 in ASC to − 0.03 ± 0.11 in ABD. Regarding reproducibility, mean differences were no statistically significant, ranging from 0.004 ± 0.06 in ASC to − 0.02 ± 0.16 in ABD. We have developed a linear model allowing accurate and reproducible prediction of SUV changes over time in the aorta and SVC.
Peptic mucosal damage induced by acute stress is a serious cause of morbidity and mortality in critically ill patients. The study aimed to investigate the protective, antioxidant and ...anti-inflammatory effects of pretreatment with Chios mastic gum (CMG), a traditionally consumed herbal resin naturally deriving from the trunk of Pistacia Lentiscus var. Chia compared to Omeprazole, a standard medication used in the prevention and treatment of gastritis, against the effects of cold restraint stress (CRS) in rat gastric and colonic mucosa.
Twenty-one male Wistar rats were randomly assigned to three groups: Control (C), Omeprazole (O), and CMG (M), according to the pre-treatment regime, and were subjected to CRS at 4
C for 3 hours. The gastric and colonic mucosal lesions were histologically assessed. ELISA measured blood concentrations of TNF-α, IL-1β, peroxidase, superoxide dismutase (SOD) and total antioxidant capacity (TEAC).
In both groups, O and M, gastric mucosal hyperemia, haemorrhagic infiltration and mucosal oedema, as well as colonic mucosal hyperaemia and haemorrhagic infiltration were significantly reduced compared to the controls (p<0.05). No significant differences were observed between Groups O and M. TNF-α levels were significantly lower in group M compared to Group O (p=0.013). IL-1β levels were significantly depressed in groups M and O compared to control (p≤ 0.001). The activity of both peroxidase and SOD enzymes decreased in group M compared to group O (p= 0.043 and p=0.047 respectively) and the control (p=0.018 and p< 0.001 respectively).
The natural Chios mastic gum is a promising nutritional supplement with protective properties to the peptic mucosa against CRS, exerting anti-inflammatory and antioxidant effects.
Nanoparticles made of a polysiloxane matrix and surrounded by 1,4,7,10-tetraazacyclododecane-1-glutaric anhydride-4,7,10-triacetic acid (DOTAGA)Gd(3+) and ...2,2'-(7-(1-carboxy-4-((2,5-dioxopyrrolidin-1-yl)oxy)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid) NODAGA(68) Ga(3+) have been synthesized for positron emission tomography/magnetic resonance (PET/MRI) dual imaging. Characterizations were carried out in order to determine the nature of the ligands available for radiolabelling and to quantify them. High radiolabelling purity (>95%) after (68) Ga labelling was obtained. The MR and PET images demonstrate the possibility of using the nanoparticles for a combined PET/MR imaging scanner. The images show fast renal elimination of the nanoparticles after intravenous injection.
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