84,048 research outputs found

    Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review

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    The positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been proposed to measure cell proliferation non-invasively in vivo. Hence, it should provide valuable information for response assessment to tumor therapies. To date, [18F]FLT uptake has found limited use as a response biomarker in clinical trials in part because a better understanding is needed of the determinants of [18F]FLT uptake and therapy-induced changes of its retention in the tumor. In this systematic review of preclinical [18F]FLT studies, comprising 174 reports, we identify the factors governing [18F]FLT uptake in tumors, among which thymidine kinase 1 plays a primary role. The majority of publications (83 %) report that decreased [18F]FLT uptake reflects the effects of anticancer therapies. 144 times [18F]FLT uptake was related to changes in proliferation as determined by ex vivo analyses. Of these approaches, 77 % describe a positive relation, implying a good concordance of tracer accumulation and tumor biology. These preclinical data indicate that [18F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies. Understanding of the parameters which influence cellular [18F]FLT uptake and retention as well as the mechanism of changes induced by therapy is essential for successful implementation of this PET tracer. Hence, our systematic review provides the background for the use of [18F]FLT in future clinical studies

    Indirect study of 19Ne states near the 18F+p threshold

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    The early E < 511 keV gamma-ray emission from novae depends critically on the 18F(p,a)15O reaction. Unfortunately the reaction rate of the 18F(p,a)15O reaction is still largely uncertain due to the unknown strengths of low-lying proton resonances near the 18F+p threshold which play an important role in the nova temperature regime. We report here our last results concerning the study of the d(18F,p)19F(alpha)15N transfer reaction. We show in particular that these two low-lying resonances cannot be neglected. These results are then used to perform a careful study of the remaining uncertainties associated to the 18F(p,a)15O and 18F(p,g)19Ne reaction rates.Comment: 18 pages, 8 figures. Accepted in Nuclear Physics

    Influence of new reaction rates on 18F production in novae

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    Gamma-ray emission from classical novae is dominated, during the first hours, by positron annihilation resulting from the beta decay of radioactive nuclei. The main contribution comes from the decay of 18F and hence is directly related to 18F formation during the outburst. A good knowledge of the nuclear reaction rates of production and destruction of 18F is required to study 18F synthesis in novae and the resulting gamma-ray emission. The rates relevant for the main mode of 18F destruction (i.e, through proton captures) have been the object of many recent experiments. However, subsequent analyses were focused on providing rates for X-ray burst nucleosynthesis not valid at nova temperatures (lower than 3.5 10^8 K). Accordingly, it is crucial to propose and discuss new reaction rates, incorporating all new experimental results, down to the domain of nova nucleosynthesis. We show that in this temperature regime, the 18F(p,gamma) and (p,alpha) reaction rates remain uncertain and deserve further experimental and theoretical efforts. Our hydrodynamic calculations including the new nuclear rates demonstrate that their impact on 18F synthesis in nova explosions is quite large and, consequently, the early gamma-ray emission from classical novae is also affected.Comment: To appear in Astron. Astrophys., 14 pages with 9 figure

    Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer

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    Background: Effective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy. Results: Breast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first–line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes. Conclusion: This study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer

    SB-18F-3320 Association for Computing Machinery

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    The 18F(p,a)15O reaction rate for application to nova gamma-ray emission

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    The 18F(p,a)15O reaction is recognized as one of the most important reaction for nova gamma-ray astronomy as it governs the early <= 511 keV emission. However, its rate remains largely uncertain at nova temperatures due to unknown low-energy resonance strengths. We report here on our last results concerning the study of the D(18F,pa)15N reaction, as well as on the determination of the 18F(p,a)15O reaction rate using the R-matrix theory. Remaining uncertainties are discussed.Comment: Contribution to the Eighth International Symposium on Nuclei in the Cosmos, Vancouver july 19-23. 4 pages and 2 figure

    A new experiment for the determination of the 18F(p,alpha) reaction rate at nova temperatures

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    The 18F(p,alpha) reaction was recognized as one of the most important for gamma ray astronomy in novae as it governs the early 511 keV emission. However, its rate remains largely uncertain at nova temperatures. A direct measurement of the cross section over the full range of nova energies is impossible because of its vanishing value at low energy and of the short 18F lifetime. Therefore, in order to better constrain this reaction rate, we have performed an indirect experiment taking advantage of the availability of a high purity and intense radioactive 18F beam at the Louvain La Neuve RIB facility. We present here the first results of the data analysis and discuss the consequences.Comment: Contribution to the Classical Novae Explosions conference, Sitges, Spain, 20-24 May 2002, 5 pages, 3 figure
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