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 ...

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Background The use of antiangiogenic therapy in conjunction with traditional chemotherapy is becoming increasingly in cancer management, but the optimal benefit of these targeted pharmaceuticals has been limited to a subset of the population treated. Improved imaging probes that permit sensitive detection and high-resolution characterization of tumor angiogenesis could improve patient risk-benefit stratification. Objectives The overarching objective of these experiments was to develop a dual modality αvβ3-targeted nanoparticle molecular imaging agent that affords sensitive nuclear detection in conjunction with high-resolution MR characterization of tumor angiogenesis. Materials and Methods In part 1, New Zealand white rabbits (n = 21) bearing 14d Vx2 tumor received either αvβ3-targeted 99mTc nanoparticles at doses of 11, 22, or 44 MBq/kg, nontargeted 99mTc nanoparticles at 22 MBq/kg, or αvβ3-targeted 99mTc nanoparticles (22 MBq/kg) competitively inhibited with unlabeled αvβ3-nanoparticles. All animals were imaged dynamically over 2 hours with a planar camera using a pinhole collimator. In part 2, the effectiveness of αvβ3-targeted 99mTc nanoparticles in the Vx2 rabbit model was demonstrated using clinical SPECT-CT imaging techniques. Next, MR functionality was incorporated into αvβ3-targeted 99mTc nanoparticles by inclusion of lipophilic gadolinium chelates into the outer phospholipid layer, and the concept of high sensitivity – high-resolution detection and characterization of tumor angiogenesis was shown using sequential SPECT-CT and MR molecular imaging with 3D neovascular mapping. Results αvβ3-Targeted 99mTc nanoparticles at 22 MBq/kg produced the highest tumor-to-muscle contrast ratio (8.56 ± 0.13, TMR) versus the 11MBq/kg (7.32 ± 0.12) and 44 MBq/kg (6.55 ± 0.07) doses, (P < 0.05). TMR of nontargeted particles at 22.2 MBq/kg (5.48 ± 0.09) was less (P < 0.05) than the equivalent dosage of αvβ3-targeted 99mTc nanoparticles. Competitively inhibition of 99mTc αvβ3-integrin-targeted nanoparticles at 22.2 MBq/kg reduced (P < 0.05) TMR (5.31 ± 0.06) to the nontargeted control contrast level. Multislice CT imaging could not distinguish the presence of Vx2 tumor implanted in the popliteal fossa from lymph nodes in the same fossa or in the contralateral leg. However, the use of 99mTc αvβ3-nanoparticles with SPECT-CT produced a clear neovasculature signal from the tumor that was absent in the nonimplanted hind leg. Using αvβ3-targeted 99mTc-gadolinium nanoparticles, the sensitive detection of the Vx2 tumor was extended to allow MR molecular imaging and 3D mapping of angiogenesis in the small tumor, revealing an asymmetrically distributed, patchy neovasculature along the periphery of the cancer. Conclusion Dual modality molecular imaging with αvβ3-targeted 99mTc-gadolinium nanoparticles can afford highly sensitive and specific localization of tumor angiogenesis, which can be further characterized with high-resolution MR neovascular mapping, which may predict responsiveness to antiangiogenic therapy.

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The nano-sized (100-500 nm) selenium has higher bioavailability and relatively lower toxicity compared to other selenium forms. The objective of the present study was to compare liver proteome profiles of broiler chicken fed with control diet without Se supplementation and diet supplemented with nano-Se with 4.25 mg/kg DM. Differential proteome analyses were performed by two-dimensional gel electrophoresis (2D-PAGE) followed by tryptic digestion and protein identification by liquid chromatography-mass spectrometry (LC-MS). Seven hundred and eight spots were detected, and 18 protein spots showed significant difference in their intensity (p < 0.05) between the two groups. In response to nano-Se supplementation, the expression of 8 proteins was higher, and 5 proteins were lower in nano-Se supplemented group compared to control group. The functions of the differentially expressed proteins indicate that the high dose of selenium supplementation induced a dietary stress. Selenium supplementation may influence the metabolism of fatty acids and carbohydrates and antioxidant system, and increase the quantity of cytoskeletal actin and the expression of actin regulatory protein as well.

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Among 31 3,4-dihydro-s-triazinobenzimidazole derivatives tested 12 compounds showed in vitro antimicrobial activity against G+ bacteria. Best results were obtained with substances containing naphthyl or halogenated phenyl group on the triazine ring. The tested derivatives had no significant in vitro antimicrobial activity against either the used G- species or fungi.