Synthesis and Characterization of New Porphyrazine-Gd(III) Conjugates as Multimodal MR Contrast Agents

Abstract

Magnetic resonance imaging (MRI) has long been used clinically and experimentally as a diagnostic tool to obtain three-dimensional, high resolution images of deep tissues. These images are enhanced by the administration of contrast agents such as paramagnetic Gd(III) complexes. Herein we describe the preparation of a series of multimodal imaging agents in which paramagnetic Gd(III) contrast agents are conjugated to a fluorescent tetrapyrrole, namely a porphyrazine (pz). Zinc metaled pzs conjugated to one, four, or eight paramagnetic Gd(III) complexes are reported. Among these conjugates, Zn-Pz-8Gd(III) exhibits an ionic relaxivity four times that of the monomeric Gd(III) agent, presumably because of increased molecular weight, and a molecular relaxivity that is approximately thirty times larger, while retaining the intense electronic absorption and emission of the unmodified pz. Unlike current clinical MR agents, ZnPz-1Gd(III) is taken up by cells. This probe demonstrates intracellular fluorescence by confocal microscopy and provides significant contrast enhancement in MR images, as well as marked phototoxicity in assays of cellular viability. These results suggest that pz agents possess a new potential for use in cancer imaging by both MRI and near-infrared (NIR) fluorescence, while acting as a platform for photodynamic therapy.

A Self‐Assembled Complex with a Titanium(IV) Catecholate Core as a Potential Bimodal Contrast Agent

“…Bimodal imaging is presently gaining a great deal of interest since it can take advantage of great spatial, temporal resolution, and unlimited tissue penetration of MRI and high sensitivity of optical imaging. [25][26][27][28] Different classes of compounds have been designed as bimodal contrast agents, for example, Gd III chelates derivatized with luminescent dyes or transition-metal complexes, [29][30][31][32] as well as functionalized Fe 3 O 4 , [33] polymer, [34] or silica [35] nanoparticles.…”

Dendrimeric Sulfanyl Porphyrazines: Synthesis, Physico‐Chemical Characterization, and Biological Activity for Potential Applications in Photodynamic Therapy

“…These properties render them suitable for potential applications in photodynamic therapy (PDT) and photodynamic diagnosis (PDD) as photosensitizers, in chemical catalysis, and in analytical chemistry as sensors . Porphyrazines that contain sulfanyl substituents reveal good solubility in common organic solvents and significant photocytotoxicities . Many years of research on sulfanyl porphyrazines led to the expansion of their periphery with various groups; for example, ether/thioether, calixarene, (tetrathiafulvalene)sulfanylethyl, 2′‐(4‐pyridoxy)ethyl, 1‐naphthylmethyl, 2′‐(ferrocenecarboxy)ethyl, and 4‐(4‐nitroimidazol‐1‐yl)butyl …”

Synthesis and characterization of a porphyrazine–Gd(III) MRI contrast agent and in vivo imaging of a breast cancer xenograft model

“…The slight paramagnetism of Cu(II) that prevents Cu–Pz–Gd(III) from being a multimodal fluorescent/MR contrast agent enhances the complex's MR effect by increasing relaxivity ( r 1 ) relative to Zn–Pz–Gd(III). This effect was observed in analogous Pz–Gd(III) conjugates but was much less pronounced . The paramagnetism of Cu and the coordination sphere might both contribute to the relaxivity difference.…”