Purpose: Development of new therapeutic drug delivery systems is an area of significant research interest. The ability to directly target a therapeutic agent to a tumor site would minimize systemic drug exposure, thus providing the potential for increasing the therapeutic index. Experimental Design: Photodynamic therapy (PDT) involves the uptake of a sensitizer by the cancer cells followed by photoirradiation to activate the sensitizer. PDTusing Photofrin has certain disadvantages that include prolonged cutaneous photosensitization. Delivery of nanoparticles encapsulated with photodynamic agent specifically to a tumor site could potentially overcome the drawbacks of systemic therapy. In this study, we have developed a multifunctional polymeric nanoparticle consisting of a surface-localized tumor vasculature targeting F3 peptide and encapsulated PDTand imaging agents. Results:The nanoparticles specifically bound to the surface of MDA-435 cells in vitro and were internalized conferring photosensitivity to the cells. Significant magnetic resonance imaging contrast enhancement was achieved in i.c. rat 9L gliomas following i.v. nanoparticle administration. Serial magnetic resonance imaging was used for determination of pharmacokinetics and distribution of nanoparticles within the tumor. Treatment of glioma-bearing rats with targeted nanoparticles followed by PDT showed a significant improvement in survival rate when compared with animals who received PDT after administration of nontargeted nanoparticles or systemic Photofrin. Conclusions:This study reveals the versatility and efficacy of the multifunctional nanoparticle for the targeted detection and treatment of cancer.Photodynamic therapy (PDT) relies on the selective uptake of a photosensitizing molecule in a tumor relative to the surrounding normal parenchyma followed by exposure to the appropriate wavelength of light to activate the photosensitizer (1). When activated by light irradiation, the photosensitizer interacts with molecular oxygen to produce a cytotoxic, shortlived species known as singlet oxygen. PDT elicits both apoptotic and necrotic responses within treated tumors and produces microvascular injury leading to inflammation and hypoxia. Photofrin, a complex mixture of porphyrin oligomers, is one of the most efficient photosensitizers approved for PDT of cancer (2). However, Photofrin can cause prolonged skin photosensitization, where patients are required to avoid direct exposure to sunlight for a period of 4 to 6 weeks. Current strategies under development include attempts to direct the photosensitizing agent to the tumor by active targeting approaches, such as peptide conjugates and antibodies (3 -7), incorporation within liposomes (8, 9), and encapsulation within polymeric nanoparticles (10 -14) in an attempt to deliver higher local concentrations at the therapeutic site.A recent report of a sub-100 nm dynamic nanoparticle platform composed of polyacrylamide, which could be loaded with a photoactivatable agent (methylene blue) for the spe...

A range of liquids suitable as quality control test objects for measuring the accuracy of clinical MRI diffusion sequences (both apparent diffusion coefficient and tensor) has been identified and characterized. The self-diffusion coefficients for 15 liquids (3 cyclic alkanes: cyclohexane to cyclooctane, 9 n-alkanes: n-octane to n-hexadecane, and 3 n-alcohols: ethanol to 1-propanol) were measured at 15-30°C using an NMR spectrometer. Values at 22°C range from 0.36 to 2.2 10 ؊9 m 2 s ؊1 . Typical 95% confidence limits are ؎2%. Temperature coefficients are 1.7-3.2 %/°C. T 1 and T 2 values at 1.5 T and proton density are given. n-tridecane has a diffusion coefficient close to that of normal white matter. The longer n-alkanes may be useful T 2 standards. Measurements from a spin-echo MRI sequence agreed to within 2%. Magn Reson Med 43:368 -374, 2000.

No abstract

Hepatic encephalopathy (HE) is defined as a metabolically induced, potentially reversible, functional disturbance of the brain that may occur in acute or chronic liver disease. Standardized nomenclature has been proposed but a standardized approach to the treatment, particularly of persistent, episodic and recurrent encephalopathy associated with liver cirrhosis has not been proposed. This review focuses on the pathogenesis and treatment of HE in patients with cirrhosis. The pathogenesis and treatment of hepatic encephalopathy in fulminant hepatic failure is quite different and is reviewed elsewhere.