Significant impact of different oxygen breathing conditions on noninvasive in vivo tumor-hypoxia imaging using [18F]-fluoro-azomycinarabino-furanoside ([18F]FAZA)

<p>Abstract</p> <p>Background</p> <p>[¹⁸F]FAZA is a PET biomarker with great potential for imaging tumor hypoxia. Aim of our study was to compare [¹⁸F]FAZA uptake in mice with subcutaneous exogenous CT26 colon carcinomas and endogenous polyoma middle-T (PyV-mT) mammary carcinomas and to analyze the influence of different breathing protocols in CT26 colon carcinomas as well as the reversibility or irreversibility of [¹⁸F]FAZA uptake.</p> <p>Methods</p> <p>We injected subcutaneous CT26 colon carcinoma or polyomavirus middle-T (PyV-mT) mammary carcinoma-bearing mice intravenously with¹⁸F-FAZA and performed PET scans 1-3 h post injection (<it>p.i.</it>). To analyze the impact of oxygen supply in CT26 carcinomas we used three different breathing protocols: (P0) air; (P1) 100% oxygen 1 h prior injection until 3 h <it>p.i.</it>; (P2) 100% oxygen breathing starting 2 min prior tracer injection until 1 h <it>p.i. </it>and during the PET scans; mice were breathing air between the 2 h and 3 h 10 min static scans. Normalized PET images were analyzed by using defined regions of interest. Finally, some mice were dissected for pimonidazole immunohistochemistry.</p> <p>Results</p> <p>There was no difference in¹⁸F-FAZA uptake 1-3 h <it>p.i. </it>between the two carcinoma types (CT26: 1.58 ± 0.45%ID/cc; PyV-mT: 1.47 ± 0.89%ID/cc, 1 h <it>p.i.</it>, tumor size < 0.5 cm³). We measured a significant tracer clearance, which was more pronounced in muscle tissue (P0). The [¹⁸F]FAZA tumor-to-muscle-ratios in CT26 colon carcinoma-bearing mice 2 h and 3 h, but not 1 h <it>p.i. </it>were significantly higher when the mice breathed air (P0: 3.56 ± 0.55, 3 h) compared to the oxygen breathing protocols (P1: 2.45 ± 0.58; P2: 2.77 ± 0.42, 3 h). Surprisingly, the breathing protocols P1 and P2 showed no significant differences in T/M ratios, thus indicating that the crucial [¹⁸F]FAZA uptake phase is during the first hour after [¹⁸F]FAZA injection. Importantly, the muscle clearance was not affected by the different oxygen breathing conditions while the tumor clearance was lower when mice were breathing air.</p> <p>Conclusion</p> <p>Exogenous CT26 colon carcinomas and endogenous polyoma middle-T (PyV-mT) mammary carcinomas showed no differences in [¹⁸F]FAZA uptake 1-3 h <it>p.i. </it>Our analysis using various breathing protocols with air (P0) and with pure oxygen (P1, P2) clearly indicate that [¹⁸F]FAZA is an appropriate PET biomarker for <it>in vivo </it>analysis of hypoxia revealing an enhanced tracer uptake in tumors with reduced oxygen supply. [¹⁸F]FAZA uptake was independent of tumor-type.</p

Association of dietary intake and dietary habits with risk of cardiovascular disease among immigrant Pakistanis living in the Netherlands

Objective: To explore the current intake/changed dietary habits being associated with risk of cardiovascular disease after migration from Pakistan to the Netherlands. Methods: Data collection started in March 2012 and ended in July 2013. Self-administered survey with respect to cardiovascular disease and dietary intake was filled by 154 adult Pakistanis. Participants were approached through festivals and community centres. Descriptive statistics was used to analyse the data. Results: There were 41 (61%) participants who reported drinking fruit juice every day, while 13 (18.6%) participants reported drinking soft drinks 5-7 days a week. In addition, 20 (30%) participants reported decreased intake of high fat/fried foods, deserts/candy/sweets and red meat, while 23 (35%) reported an increased intake of soft drinks and convenience foods, as far as high calorie and refined food items were considered, after migration. Conclusion The study showed significant changes in dietary habits, both favourable and unfavourable, being associated with risk of cardiovascular diseases among immigrant Pakistanis living in The Netherlands

Artykuł oryginalnyZwiązek pomiędzy otyłością a drożnością tętniczych pomostów wieńcowych w obserwacji odległej

Background: Arterial conduits having long-term patency rates have been increasingly used for bypass of coronary arteries although some risk factors for their occlusion such as recipient vessel size, older age, and hyperlipidaemia have been described. Obesity, on the other hand, has been well established as a coronary risk factor. However, the effects of obesity on patency of arterial conduits, especially the internal mammary artery, have not been studied previously. Aim: To assess the long-term effects of obesity on left internal mammary artery (LIMA) patency. Methods: Angiograms of all patients with a LIMA conduit only were analysed. Two groups were formed according to the LIMA patency: group 1 &#8211; patients with occluded LIMA (n = 59), and group 2 &#8211; patients with patent LIMA (n = 68). Baseline demographic, haemodynamic, and laboratory characteristics of patients in both groups were compared. Obesity was defined as body mass index ł 30 kg/m2. Results: The mean BMI value in group 1 was significantly higher than in group 2 (30.4 &plusmn; 3.1 vs. 28.7 &plusmn; 4.7, p = 0.025). The two groups differed in time from surgery, drug use, and HDL cholesterol level. In addition, patients in both groups were categorised by BMI, and obese and non-obese groups were formed. Higher BMI was significantly associated with LIMA occlusion such that 71% of patients in group 1 had increased BMI, compared with 25% of patients in group 2 (p < 0.001). Multivariate analysis showed that multiple adjusted OR of the risk of LIMA occlusion was 7.41 (95% CI 3.38-16.28) for patients with increased BMI. Conclusions: : Obesity (ł 30 kg/m2) has a significant and independent negative effect on the patency of the LIMA graft.Wstęp: Z uwagi na wysoki odsetek zachowanej po wielu latach drożności pomosty tętnicze są preferowanym sposobem wykonywania operacji rewaskularyzacyjnych (CABG). Istnieją pewne czynniki zwiększające ryzyko zamknięcia, do których należą przekrój naczynia chorego, wiek oraz hiperlipidemia. Z kolei otyłość jest dobrze udokumentowanym czynnikiem ryzyka choroby wieńcowej. Dotychczas związek pomiędzy otyłością a drożnością pomostów tętniczych, szczególnie z wykorzystaniem tętnicy piersiowej wewnętrznej (LIMA), nie był badany. Cel: Ocena związku pomiędzy otyłością a drożnością pomostów tętniczych w obserwacji długoterminowej. Metody: Poddano analizie angiogramy wszystkich chorych z LIMA. Biorąc pod uwagę drożność LIMA, utworzono dwie grupy chorych: grupa 1 &#8211; chorzy z zamkniętym pomostem (n = 59), oraz grupa 2 &#8211; chorzy z drożną LIMA (n = 68). Porównano dane demograficzne, hemodynamiczne i laboratoryjne obu grup. Otyłość zdefiniowano jako indeks masy ciała (BMI) ł 30 kg/m2. Wyniki: Średnia wartość BMI w grupie 1 była istotnie wyższa niż w grupie 2 (30,4 &plusmn; 3,1 vs 28,7 &plusmn; 4,7, p = 0,025). Obie grupy różniły się również pod względem czasu, który upłynął od zabiegu chirurgicznego, stosowanych leków i stężenia HDL-cholesterolu. Dodatkowo chorych podzielono na otyłych i nieotyłych. Otyłość wiązała się ze zwiększonym ryzykiem zamknięcia LIMA: stwierdzono ją u 71% chorych z grupy 1 wobec 25% z grupy 2 (p < 0,001). Analiza wieloczynnikowa wykazała, że ryzyko zamknięcia LIMA było 7,41 razy wyższe u chorych otyłych (95% CI 3,38&#8211;16,28). Wnioski: Otyłość jest istotnym i niezależnym czynnikiem ryzyka zamknięcia pomostu tętniczego w obserwacji odległej

Fine vs. coarse atrial fibrillation: Which one is more risky?

Background: Atrial fibrillation (AF) is a frequent arrhythmia, associated with morbidity and mortality. It is identified by two types on surface electrocardiogram as fine and coarse AF. We aimed to search the association of subtypes of AF with clinical parameters. Methods: Eight hundred and eleven consecutive patients, who had AF attack which lasted longer than 24 h or more, were evaluated along with clinical and laboratory data. Results: Coarse AF was noticed in 51.7% (n = 419), and fine AF in 48.3% (n = 392). Sex was associated with subtype of AF such that coarse AF was present in 46.5% of male patients, but in 56.1% of female patients (p = 0.009). Coarse AF was present in 85.3% of patients with mitral stenosis, whereas it was present in 35.3% of patients with normal heart valve (p < 0.001).). Patients having fine AF were significantly older than those having coarse AF (64 +/- 12, 57 +/- 13 years, p < 0.001). 19.6% of those with coarse AF had history of cerebrovascular event (CVE), whereas 13.5% of those with fine AF had history of CVE (p = 0.021). After controlling for age in the multivariable logistic regression analysis, presence of coarse AF (B = 1.585, p = 0.031) was found to be independently associated with the history of CVE. Conclusion: AF is identified by two morphological forms on the surface electrocardiogram. These two forms were found to be associated with different clinical parameters, acting on vascular endpoints differently. Copyright (c) 2007 S. Karger AG, Basel

Cu-64 antibody-targeting of the T-cell receptor and subsequent internalization enables in vivo tracking of lymphocytes by PET

T cells are key players in inflammation, autoimmune diseases, and immunotherapy. Thus, holistic and noninvasive in vivo characterizations of the temporal distribution and homing dynamics of lymphocytes in mammals are of special interest. Herein, we show that PET-based T-cell labeling facilitates quantitative, highly sensitive, and holistic monitoring of T-cell homing patterns in vivo. We developed a new T-cell receptor (TCR)-specific labeling approach for the intracellular labeling of mouse T cells. We found that continuous TCR plasma membrane turnover and the endocytosis of the specific (64)Cu-monoclonal antibody (mAb)–TCR complex enables a stable labeling of T cells. The TCR–mAb complex was internalized within 24 h, whereas antigen recognition was not impaired. Harmful effects of the label on the viability, DNA-damage and apoptosis-necrosis induction, could be minimized while yielding a high contrast in in vivo PET images. We were able to follow and quantify the specific homing of systemically applied (64)Cu-labeled chicken ovalbumin (cOVA)-TCR transgenic T cells into the pulmonary and perithymic lymph nodes (LNs) of mice with cOVA-induced airway delayed-type hypersensitivity reaction (DTHR) but not into pulmonary and perithymic LNs of naïve control mice or mice diseased from turkey or pheasant OVA-induced DTHR. Our protocol provides consequent advancements in the detection of small accumulations of immune cells in single LNs and specific homing to the sites of inflammation by PET using the internalization of TCR-specific mAbs as a specific label of T cells. Thus, our labeling approach is applicable to other cells with constant membrane receptor turnover