Earlier tumor detection can improve 5-year survival of patients, particularly among those presenting with cancers less than 1 cm in diameter. a m b 3 - Targeted 111 In nanoparticles (NP) were developed and studied for detection of tumor angiogenesis. Studies were conducted in New Zealand white rabbits implanted 12 days earlier with Vx-2 tumor. a m b 3 - Targeted 111 In/NP bearing 10 111In/NP vs. 1 111In/NP nuclide payloads were compared to nontargeted radiolabeled control particles. In vivo competitive binding studies were used to assess ligand-targeting specificity. a m b 3 -Integrin-targeted NP with 10 111In/NP provided better (p < 0.05) tumor-to-muscle ratio contrast (6.3 6 0.2) than 1 111In/NP (5.1 6 0.1) or nontargeted particles with 10 111In/NP (3.7 6 0.1) over the initial 2-hr postinjection. At 18 hr, mean tumor activity in rabbits receiving a m b 3 -integrin-targeted NP was 4-fold higher than the nontargeted control. Specificity of the NP for the tumor neovasculature was supported by in vivo competition studies and by fluorescence microscopy of a m b 3 -targeted fluorescent-labeled NP. Biodistribution studies revealed that the primary clearance organ in rabbits as a %ID/g tissue was the spleen. Circulatory half-life (t 1/2b ) was estimated to be 5 hr using a 2-compartment model. a m b 3 - Targeted 111 In perfluorocarbon NP may provide a clinically useful tool for sensitively detecting angiogenesis in nascent tumors, particularly in combination with secondary highresolution imaging modalities, such as MRI. ' 2007 Wiley-Liss, Inc.Key words: indium; angiogenesis; integrin; nanoparticles; Vx2; cancer Data accumulated over the last 25 years in the surveillance, epidemiology and end results cancer registry support the principle that earlier tumor detection improves 5-year survival of patients with either localized or regional invasive breast carcinoma. 1 Improvements in survival were correlated with an overall downward shift in tumor size distribution, with particular advantage noted among patients presenting with cancers less than 1 cm. A widespread desire to detect and treat cancer earlier has spawned interest in molecular imaging and genomic-proteomic technologies, which in combination with new strategies to treat cancer may further improve cancer survival.One approach to identifying small solid tumors has involved early detection of angiogenesis by targeting unique biosignatures of neovascular endothelium, such as a v b 3 -integrin. We have previously demonstrated that paramagnetic perfluorocarbon emulsions targeted to the a v b 3 -integrin can be used to detect the neovasculature of tumors 30 mm 3 at clinical field strengths (1.5 T). Because perfluorocarbon nanoparticles (NP) have a nominal particle size of 250 nm and are constrained within the vasculature, access to a v b 3 -integrin expressed on extravascular macrophages, smooth muscle and other cells is sterically precluded. MRI provides outstanding high-resolution images of even minute tumors enhanced by the bound paramagnetic NP; however, the ...
Abstract. The Cosmic Ray Isotope Spectrometer is designed to cover the highest decade of the Advanced Composition Explorer's energy interval, from 50 to 500 MeV/nucleon, with isotopic resolution for elements from Z ' 2 to Z ' 30. The nuclei detected in this energy interval are predominantly cosmic rays originating in our Galaxy. This sample of galactic matter can be used to investigate the nucleosynthesis of the parent material, as well as fractionation, acceleration, and transport processes that these particles undergo in the Galaxy and in the interplanetary medium.Charge and mass identification with CRIS is based on multiple measurements of dE=dx and total energy in stacks of silicon detectors, and trajectory measurements in a scintillating optical fiber trajectory (SOFT) hodoscope. The instrument has a geometrical factor of 250 cm 2 sr for isotope measurements, and should accumulate 5 10 6 stopping heavy nuclei (Z 2) in two years of data collection under solar minimum conditions.
The abundance of Li, Be, and B isotopes in galactic cosmic rays (GCR) between E=50-200 MeV/nucleon has been observed by the Cosmic Ray Isotope Spectrometer (CRIS) on NASA's ACE mission since 1997 with high statistical accuracy. Precise observations of Li, Be, B can be used to constrain GCR propagation models. We find that a diffusive reacceleration model with parameters that best match CRIS results (e.g. B/C, Li/C, etc) are also consistent with other GCR observations. A ∼15-20% overproduction of Li and Be in the model predictions is attributed to uncertainties in the production cross-section data. The latter becomes a significant limitation to the study of rare GCR species that are generated predominantly via spallation.
Measurements of the abundances of cosmic-ray 59 Ni and 59 Co are reported from the Cosmic-Ray Isotope Spectrometer (CRIS) on the Advanced Composition Explorer. These nuclides form a parent-daughter pair in a radioactive decay which can occur only by electron capture. This decay cannot occur once the nuclei are accelerated to high energies and stripped of their electrons. The CRIS data indicate that the decay of 59 Ni to 59 Co has occurred, leading to the conclusion that a time longer than the yr half-life of 59 Ni elapsed before the particles 4 7.6 # 10 were accelerated. Such long delays indicate the acceleration of old, stellar or interstellar material rather than fresh supernova ejecta. For cosmic-ray source material to have the composition of supernova ejecta would require that these ejecta not undergo significant mixing with normal interstellar gas before ∼10 5 yr has elapsed.
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