85,896 research outputs found
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18F-FAC PET Visualizes Brain-Infiltrating Leukocytes in a Mouse Model of Multiple Sclerosis.
Brain-infiltrating leukocytes contribute to multiple sclerosis (MS) and autoimmune encephalomyelitis and likely play a role in traumatic brain injury, seizure, and stroke. Brain-infiltrating leukocytes are also primary targets for MS disease-modifying therapies. However, no method exists for noninvasively visualizing these cells in a living organism. 1-(2'-deoxy-2'-18F-fluoroarabinofuranosyl) cytosine (18F-FAC) is a PET radiotracer that measures deoxyribonucleoside salvage and accumulates preferentially in immune cells. We hypothesized that 18F-FAC PET could noninvasively image brain-infiltrating leukocytes. Methods: Healthy mice were imaged with 18F-FAC PET to quantify if this radiotracer crosses the blood-brain barrier (BBB). Experimental autoimmune encephalomyelitis (EAE) is a mouse disease model with brain-infiltrating leukocytes. To determine whether 18F-FAC accumulates in brain-infiltrating leukocytes, EAE mice were analyzed with 18F-FAC PET, digital autoradiography, and immunohistochemistry, and deoxyribonucleoside salvage activity in brain-infiltrating leukocytes was analyzed ex vivo. Fingolimod-treated EAE mice were imaged with 18F-FAC PET to assess if this approach can monitor the effect of an immunomodulatory drug on brain-infiltrating leukocytes. PET scans of individuals injected with 2-chloro-2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosyl-adenine (18F-CFA), a PET radiotracer that measures deoxyribonucleoside salvage in humans, were analyzed to evaluate whether 18F-CFA crosses the human BBB. Results: 18F-FAC accumulates in the healthy mouse brain at levels similar to 18F-FAC in the blood (2.54 ± 0.2 and 3.04 ± 0.3 percentage injected dose per gram, respectively) indicating that 18F-FAC crosses the BBB. EAE mice accumulate 18F-FAC in the brain at 180% of the levels of control mice. Brain 18F-FAC accumulation localizes to periventricular regions with significant leukocyte infiltration, and deoxyribonucleoside salvage activity is present at similar levels in brain-infiltrating T and innate immune cells. These data suggest that 18F-FAC accumulates in brain-infiltrating leukocytes in this model. Fingolimod-treated EAE mice accumulate 18F-FAC in the brain at 37% lower levels than control-treated EAE mice, demonstrating that 18F-FAC PET can monitor therapeutic interventions in this mouse model. 18F-CFA accumulates in the human brain at 15% of blood levels (0.08 ± 0.01 and 0.54 ± 0.07 SUV, respectively), indicating that 18F-CFA does not cross the BBB in humans. Conclusion: 18F-FAC PET can visualize brain-infiltrating leukocytes in a mouse MS model and can monitor the response of these cells to an immunomodulatory drug. Translating this strategy into humans will require exploring additional radiotracers
Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review
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
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Role of Positron Emission Tomography in Imaging of Non-neurologic Disorders of the Head, Neck, and Teeth in Veterinary Medicine.
Positron Emission Tomography (PET) is an imaging technique that provides functional information, in addition to structural information obtained with computed tomography (CT). The most common application is cancer staging, using 18F-Fluorodeoxyglucose (18F-FDG), a radioactive analog of glucose. Although limited data are available in the veterinary literature, human studies have demonstrated benefit with the addition of PET both for assessment of the primary tumor and for detection of metastatic disease. 18F-FDG PET appears to be more accurate at detecting the margin of oral neoplasia, in particular for tumors arising from highly vascularized tissue, such as the lingual and laryngeal areas. 18F-FDG PET has a high sensitivity for the detection of lymph node metastasis, however the specificity is variable between studies. Tracers beyond 18F-FDG can also be used for oncology imaging. 18F-Fluoride (18F-NaF) is an excellent osseous tracer, useful in assessing bone involvement of primary tumors or osseous metastasis. Other specific tracers can be used to assess cell proliferation or hypoxia for tumor characterization. 18F-FDG is also an excellent tracer for detection of inflammation. Human studies have demonstrated its value for the assessment of periodontitis and dental implant infection. 18F-NaF has been used to assess disorders of the temporomandibular joint in the human literature, demonstrating good correlation with arthralgia and therapeutic outcome. Both 18F-NaF and 18F-FDG had good concordance with localization of cervical pain in people. PET will likely have a growing role in veterinary medicine not only for oncologic imaging but also for assessment of inflammation and pain
Indirect study of 19Ne states near the 18F+p threshold
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
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
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Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET).
BackgroundConventional scale production of small batches of PET tracers (e.g. for preclinical imaging) is an inefficient use of resources. Using O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), we demonstrate that simple microvolume radiosynthesis techniques can improve the efficiency of production by consuming tiny amounts of precursor, and maintaining high molar activity of the tracers even with low starting activity.ProceduresThe synthesis was carried out in microvolume droplets manipulated on a disposable patterned silicon "chip" affixed to a heater. A droplet of [18F]fluoride containing TBAHCO3 was first deposited onto a chip and dried at 100 °C. Subsequently, a droplet containing 60 nmol of precursor was added to the chip and the fluorination reaction was performed at 90 °C for 5 min. Removal of protecting groups was accomplished with a droplet of HCl heated at 90 °C for 3 min. Finally, the crude product was collected in a methanol-water mixture, purified via analytical-scale radio-HPLC and formulated in saline. As a demonstration, using [18F]FET produced on the chip, we prepared aliquots with different molar activities to explore the impact on preclinical PET imaging of tumor-bearing mice.ResultsThe microdroplet synthesis exhibited an overall decay-corrected radiochemical yield of 55 ± 7% (n = 4) after purification and formulation. When automated, the synthesis could be completed in 35 min. Starting with < 370 MBq of activity, ~ 150 MBq of [18F]FET could be produced, sufficient for multiple in vivo experiments, with high molar activities (48-119 GBq/μmol). The demonstration imaging study revealed the uptake of [18F]FET in subcutaneous tumors, but no significant differences in tumor uptake as a result of molar activity differences (ranging 0.37-48 GBq/μmol) were observed.ConclusionsA microdroplet synthesis of [18F]FET was developed demonstrating low reagent consumption, high yield, and high molar activity. The approach can be expanded to tracers other than [18F]FET, and adapted to produce higher quantities of the tracer sufficient for clinical PET imaging
Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer
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
The 18F(p,a)15O reaction rate for application to nova gamma-ray emission
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
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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