390 research outputs found
Tumour hypoxia imaging with [F-18]FAZA PET in head and neck cancer patients: a pilot study
No full textPurpose Hypoxia is an important negative prognostic factor for radiation treatment of head and neck cancer. This study was performed to evaluate the feasibility of use of F-18-labelled fluoroazomycin arabinoside ([F-18]FAZA) for clinical PET imaging of tumour hypoxia. Methods Eleven patients (age 59.6 +/- 9 years) with untreated advanced head and neck cancer were included. After injection of approximately 300 MBq of [F-18]FAZA, a dynamic sequence up to 60 min was acquired on an ECAT HR+ PET scanner. In addition, approximately 2 and 4 h p.i., static whole-body PET (n=5) or PET/CT (n=6) imaging was performed. PET data were reconstructed iteratively (OSEM) and fused with CT images (either an external CT or the CT of integrated PET/CT). Standardised uptake values (SUVs) and tumour-to-muscle (T/M) ratios were calculated in tumour and normal tissues. Also, the tumour volume displaying a T/M ratio > 1.5 was determined. Results Within the first 60 min of the dynamic sequence, the T/M ratio generally decreased, while generally increasing at later time points. At 2 h p.i., the tumour SUVmax and SUVmean were found to be 2.3 +/- 0.5 (range 1.5-3.4) and 1.4 +/- 0.3 (range 1.0-2.1), respectively. The mean T/M ratio at 2 h p.i. was 2.0 +/- 0.3 (range 1.6-2.4). The tumour volume displaying a T/M ratio above 1.5 was highly variable. At 2 h p.i., [F-18]FAZA organ distribution was determined as follows: kidney > gallbladder > liver > tumour > muscle > bone > brain > lung. Conclusion [F-18]FAZA PET imaging appears feasible in head and neck cancer patients, and the achieved image quality is adequate for clinical purposes. Based on our initial results, [F-18]FAZA warrants further evaluation as a hypoxia PET tracer for imaging of cancer
Hypoxia-specific tumor imaging with F-18-fluoroazomycin arabinoside
No full textThe study was performed to compare the F-18-labeled nitroimidazole compound fluoroazomycin arabinoside (F-18-FAZA) with the standard hypoxia tracer fluoromisonidazole (F-18-FMISO) in detection of tumor tissue hypoxia and to verify the oxygenation dependency of F-18-FAZA uptake. Methods: Biodistribution of F-18-FAZA was studied at various time points in EMT6 tumor-bearing BALB/c mice and in AR42J and A431 tumor-bearing nude mice and compared with that of F-18-FMISO. The presence of tumor tissue hypoxia was verified in 5 EMT6 and 5 AR42J tumors using an oxygen-sensing needle electrode system. To evaluate the oxygenation dependency of F-18-FAZA uptake, using the Munich prototype animal PET scanner, 2 serial PET scans were performed in 13 A431 tumor-bearing nude mice breathing pure oxygen or room air on 1 d and then selecting the other oxygen breathing condition on the following day. In addition, digital autoradiography was performed with EMT6 tumor-bearing F-18-FAZA-dosed, nude mice breathing either room air (n = 8) or carbogen (n = 9). Results: Tissue partial pressure of oxygen (Po-2) electrode measurements revealed that tumor hypoxia was present under room air breathing in EMT6 (tissue Po-2 = 2.9 +/- 2.6) and AR42J tumors (tissue Po-2 = 0.4 +/- 0.2), which was significantly lower compared with that of reference tissue (tissue Po-2 = 25.8 +/- 6.7 and tissue Po-2 29.0 +/- 3.0 [mean +/- SD], respectively; P < 0.01). In all tumor models, F-18-FAZA displayed significantly higher tumor-to-muscle and tumor-to-blood ratios compared with F-18-FMISO, indicating a faster clearance of F-18-FAZA from normal tissues. In AR42J tumors, F-18-FAZA tumor-to-normal ratios were found to increase overtime. Serial animal F-18-FAZA PET studies showed that the tumor-to-background ratio was significantly higher in animals breathing room air compared with that of animals breathing pure oxygen (7.3 +/- 2.3 vs. 4.2 +/- 1.2, respectively; P < 0.001). Similarly, autoradiography showed significantly higher tumor-to-muscle ratios in mice breathing room air compared with those of animals breathing carbogen (5.3 +/- 0.8 vs. 2.2 +/- 0.8; respectively; P < 0.02). Conclusion: F-18-FAZA shows superior biokinetics and is, thus, a promising PET tracer for the visualization of tumor hypoxia. This study also verified a hypoxia-specific uptake mechanism for F-18-FAZA in murine tumor models
Peningkatan efisiensi lintasan produksi dengan metode line balancing Kilbridge & Wester
No full textIn the manufacturing industry, production line efficiency is an important factor to maximize output and reduce delays. One of the methods used to achieve this goal is line balancing. This research aims to maximize output and reduce balance delay using the Killbridge and Wester line balancing method. The Killbridge and Wester method is used to analyze and balance the production line by combining several operations into one work station, so that the operating time at each station is reduced and more balanced. The results showed a significant increase in production line efficiency. As a result of the author's line balancing, the line efficiency increased from 65.76% to 84.55%, and the smoothest index decreased from 7.33 to 2.77. The author succeeded in combining several operations into one workstation that was more balanced in terms of operating time. The line balancing analysis process that has been analysis process that has been carried out shows an increase in output and a reduction in production time, however still requires further testing to calculate the optimum number of operators at each workstation. in each work station. The line balancing that was carried out proved to be effective in improving production efficiency.Dalam industri manufaktur, efisiensi lini produksi merupakan faktor penting untuk memaksimalkan output dan mengurangi penundaan. Salah satu metode yang digunakan untuk mencapai tujuan ini adalah line balancing. Penelitian ini bertujuan untuk memaksimalkan output dan mengurangi balance delay pada sebuah perusahaan elektronik karena perusahaan mengalami beberapa penundaan yaitu conveyor produksi berhenti akibat penumpukan di salah satu proses. Metode Kilbridge & Wester digunakan untuk menganalisis dan menyeimbangkan lini produksi dengan menggabungkan beberapa operasi menjadi satu stasiun kerja, sehingga waktu operasi di setiap stasiun kerja lebih seimbang. Hasil penelitian menunjukkan peningkatan signifikan pada efisiensi lini produksi. Hasil dari line balancing menunjukkan line efficiency meningkat dari 65,76% menjadi 84,55%, dan smoothest index menurun dari 7,33 menjadi 2,77. Penggabungan beberapa operasi menjadi satu stasiun kerja membuat beban lebih seimbang dalam hal waktu operasi. Proses analisis line balancing yang telah dilakukan menunjukkan peningkatan output dan pengurangan waktu produksi, tetapi masih memerlukan tahap uji coba lanjutan untuk menghitung jumlah operator optimum di setiap stasiun kerja
Design, synthesis, and functionalization of dimeric peptides targeting chemokine receptor CXCR4.
No full textItem does not contain fulltextThe chemokine receptor CXCR4 is a critical regulator of inflammation and immune surveillance, and it is specifically implicated in cancer metastasis and HIV-1 infection. On the basis of the observation that several of the known antagonists remarkably share a C(2) symmetry element, we constructed symmetric dimers with excellent antagonistic activity using a derivative of a cyclic pentapeptide as monomer. To optimize the binding affinity, we investigated the influence of the distance between the monomers and the pharmacophoric sites in the synthesized constructs. The affinity studies in combination with docking computations support a two-site binding model. In a final step, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was introduced as chelator for (radio-)metals, thus allowing to exploit these compounds as a new group of CXCR4-binding peptidic probes for molecular imaging and endoradiotherapeutic purposes. Both the DOTA conjugates and some of their corresponding metal complexes retain good CXCR4 affinity, and one (68)Ga labeled compound was studied as PET tracer
Nuclear imaging probes: from bench to bedside.
No full textThe availability of specific imaging probes is the nuclear fuel for molecular imaging by positron emission tomography and single-photon emission computed tomography. These two radiotracer-based imaging modalities represent the prototype methods for noninvasive depiction and quantification of biochemical processes, allowing a functional characterization of tumor biology. A variety of powerful radiolabeled probes--tracers--are already established in the routine clinical management of human disease and others are currently subject to clinical assessment. Emerging from investigations of the genomic and proteomic signatures of cancer cells, an increasing number of promising targets are being identified, including receptors, enzymes, transporters, and antigens. Corresponding probes for these newly identified targets need to be developed and transferred into the clinical setting. Starting with a brief summary of the characteristics and prerequisites for a "good tracer," an overview of tracer concepts, target selection, and development strategies is given. The influence of the imaging concepts on tracer development is also discussed
A Conformationally Frozen Peptoid Boosts CXCR4 Affinity and Anti-HIV Activity.
No full textThere can be only one: Using a peptoid motif obtained by shifting the arginine side chain of a pentapeptide previously developed by Fujii et al. to the neighboring nitrogen atom restricts the conformational freedom and yields a conformationally homogeneous peptide (see picture) with a 100-fold higher binding affinity to the chemokine receptor CXCR4 in the picomolar range. Its efficiency to inhibit HIV-1 infections is also demonstrated. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PD recurrence in cavities at different energizing methods
No full textElectrical Engineering, Mathematics and Computer Scienc
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