Molecular and functional imaging technology for the development of efficient treatment strategies for gliomas.

Gliomas are the most common types of brain tumors, which invariably lead to death over months or years. Before new and potentially more effective treatment strategies, such as gene therapy, can be effectively introduced into clinical application the following goals must be reached: (1) the determination of localization, extent and metabolic activity of the glioma; (2) the assessment of functional changes within the surrounding brain tissue; (3) the identification of genetic changes on the molecular level leading to disease; and in addition (4) a detailed non-invasive analysis of both endogenous and exogenous gene expression in animal models and in the clinical setting. Non-invasive imaging of endogenous gene expression by means of positron emission tomography (PET) may reveal insight into the molecular basis of pathogenesis and metabolic activity of the glioma and the extent of treatment response. When exogenous genes are introduced to serve for a therapeutic function, PET imaging techniques may reveal the assessment of the location, magnitude and duration of therapeutic gene expression and its relation to the therapeutic effect. Here, we review the main principles of PET imaging and its key roles in neurooncology research.

A new polysaccharide macromolecular contrast agent for MR imaging: biodistribution and imaging characteristics.

The aims of this study were to characterize certain physicochemical, pharmacokinetic, and enhancement properties of a new macromolecular contrast agent, carboxymethyl hydroxyethyl starch-(Gd-DO3A)(35) [CMHES-(Gd-DO3A)(35)], consisting of a polysaccharide backbone covalently derivatized with multiple macrocyclic chelating groups for gadolinium. CMHES-(Gd-DO3A)(35) has an average molecular weight of 72 kD and a plasma half-time of 8.4 hours. T1 and T2 relaxivities are 14.1 +/- 0.1 L mmol(-1) * sec(-1) and 17.8 +/- 0.9 L mmol(-1) * sec(-1), respectively, for each gadolinium ion measured at 39 degrees C and 20 Mhz; this T1 relaxivity is more than 4 times that of gadopentetate. Seven days after intravenous administration only relatively small amounts of gadolinium could be detected in blood or other tissues of rats. The compound was well tolerated in diagnostic dosages by all experimental animals. Magnetic resonance angiography performed within 1 hour of CMHES-(Gd-DO3A)(35) administration showed a near-constant and strong enhancement of blood in arteries and veins. Analysis of dynamic enhancement patterns of experimental tumors (MAT-LyLu prostate cancer implanted in rats) following intravenous CMHES-(Gd-DO3A)(35) administration yielded quantitative estimates of tumor plasma volume and microvessel permeability; the demonstrated hyperpermeability of tumor microvessels was easily distinguished from the absence of measurable microvascular permeability in non-neoplastic soft tissues.