Magnetic nanoparticles (MNP) can be used as contrast-enhancing agents to visualize tumors by magnetic resonance imaging (MRI). Here we describe an easy synthesis method of magnetic nanoparticles coated with polyethylene glycol (PEG) and demonstrate size-dependent accumulation in murine tumors following intravenous injection. Biocompatible iron oxide MNPs coated with PEG were prepared by replacing oleic acid with a biocompatible and commercially available silane-PEG to provide an easy and effective method for chemical coating. The colloidal stable PEGylated MNPs were magnetically separated into two distinct size subpopulations of 20 and 40 nm mean diameters with increased phagocytic uptake observed for the 40 nm size range in vitro. MRI detection revealed greater iron accumulation in murine tumors for 40 nm nanoparticles after intravenous injection. The enhanced MRI contrast of the larger MNPs in the tumor may be a combined result of the size-dependent extravasation and capture by macrophages in the tumor, providing important considerations for improved bioimaging approaches.

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Antiangiogenic therapies are being pursued as a means of starving tumors of their energy supply. Although numerous studies show that such therapies render tumors hypoxic, just as many studies have, surprisingly, shown improved tumor oxygenation. These contradicting findings challenge both the original rationale for antiangiogenic therapy and our understanding of the physiology of tissue oxygenation. The flow-diffusion equation, which describes the relation between blood flow and the extraction of freely diffusible molecules in tissue, was recently extended to take the heterogeneity of capillary transit times (CTH) into account. CTH is likely to be high in the chaotic microvasculature of a tumor, increasing the effective shunting of blood through its capillary bed. We review the properties of the extended flowdiffusion equation in tumor tissue. Elevated CTH reduces the extraction of oxygen, glucose, and cytotoxic molecules. The extent to which their net extraction is improved by antiangiogenic therapy, in turn, depends on the extent to which CTH is normalized by the treatment. The extraction of oxygen and glucose are affected to different extents by elevated CTH, and the degree of aerobic glycolysis-known as the Warburg effect-is thus predicted to represent an adaptation to the CTH of the local microvasculature. Cancer Res; 73(18); 5618-24. Ó2013 AACR.

Abstract-Hypertension is associated with reduced coronary vasodilatory capacity, possibly caused by structural changes in the coronary resistance vessels. Because vasodilatory treatment may correct abnormal structure better than nonvasodilating treatment, we compared whether long-term angiotensin-converting enzyme (ACE) inhibition has a greater effect on coronary reserve and cardiovascular structure than ␤-blockade in patients with essential hypertension. Thirty previously untreated hypertensive patients were randomized in a double-blind design to treatment for 1 year with either perindopril (4 to 8 mg per day, nϭ15) or atenolol (50 to 100 mg per day, nϭ15) and furthermore compared with normotensive controls. Cardiac output and left ventricular mass were measured with echocardiography and resistance artery structure was determined in vitro. Using positron emission tomography, myocardial perfusion (MP) was determined at rest and during dipyridamole-induced hyperemia while still on medication. Perindopril reduced left ventricular mass by 14Ϯ4% (PϽ0.01), peripheral vascular resistance by 12Ϯ6% (PϽ0.01), and media thickness-tolumen diameter ratio of resistance arteries by 16Ϯ4% (PϽ0.05), whereas atenolol had no effect.