Synthese und Charakterisierung amphiphiler Porphyrinoide als Kontrastmittel für das Magnetic Resonance Imaging (MRI)

Abstract

Magnetic resonance imaging (MRI) is a diagnostic tool, which is commonly used in visualization of internal procedures in the living tissue. Used in visualizing procedures, MRI shows an increased contrast-enhancing effect in soft tissue in contrast to other techniques like computer tomography (CT). MRI does not need any ionizing radiation and provides three dimensional tomographic shots. One of the first commonly used porphyrin-based contrast agents was Gadophrin-2, which has a high affinity to necrotic tissue. It is a gadolinium-based contrast agent and consists of two Gd-DTPA (gadolinium (III)-diethylentriaminepentaacetic acid) units. Gadolinium has a high degree of paramagnetism due to its seven unpaired electrons. Thus, the T1 relaxation rates of the first and second watersphere increases considerably. In addition to the diagnostic method MRI, the localization therapy PDT (photodynamic therapy) is used for an early detection and treatment of cancer. In photodynamic therapy, cytotoxic singlet oxygen is created by exposing a photosensitizer with a specific wavelength of light. One of the first photosensitizers was photofrin, which is still used in treatment of cancer. Some limitations of photofrin are a low molar absorption coefficient and a skin photosensitivity resulting from delocalization throughout the skin. Thus, new photosensitizers with absorption at longer wavelengths and effective localization are needed. A combinated application of new contrast agents for both image-guided diagnostic MRI and localization therapy PDT should be the aim of research. Porphyrin- and chlorin-based agents, combining these requirements absorb at wavelengths of more than 640 nm and offer a high number of paramagnetic units. Representatives of porphyrin class are conjugated with tetraaza chelates, which are known from clinical applied agents like Magnevist® (Gd-DTPA) and Dotarem® (Gd-DOTA, gadolinium (III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-acetic acid). These chelates show a high affinity to lanthanide ions and are able to conjugate to one or two water molecules.