Dendrimers as carriers for contrast agents in magnetic resonance imaging

Abstract

Magnetic resonance imaging (MRI) is a non-invasive clinical imaging modality, which has become widely used in the diagnosis of human diseases around the world. Some MRI exams include the use of contrast agents. The goal of an ideal MRI contrast agent involves the tissue-or organ-targeting materials with high relaxivity and specificity, low toxicity and side effects, suitable long intravascular duration and excretion time and high contrast enhancement with low doses, in vivo, all coupled to low overall cost. Dendrimers are synthetic, highly branched, mono-disperse macromolecules of nanometer dimensions. Properties associated with these dendrimers such as uniform size, water solubility, modifiable surface functionality and available internal cavities make them candidates for ideal carriers of MRI contrast agents. The research progress of the dendritic contrast agents is discussed. magnetic resonance imaging (MRI), contrast agents, paramagnetic metal chelates, dendrimers, tissue or organ-targetingCitation: Yan G P, Ai C W, Li L, et al. Dendrimers as carriers for contrast agents in magnetic resonance imaging. Magnetic resonance imaging (MRI) has been widely used as a non-invasive clinical imaging modality in hospitals around the world, since it was developed in 1973 and received FDA approval for clinical use in 1985. At present, MRI is widely used for the diagnosis and investigation of human diseases, such as necrotic tissues, infarcted arteries and malignant diseases. Paul C. Lauterbur and Sir Peter Mansfield won the Nobel Prize in physiology and medicine in 2003 for their discoveries concerning MRI [1,2].Magnetic resonance imaging relies on the detection of nuclear magnetic resonance (NMR) signals emitted by hydrogen protons of waters in the body placed in a magnetic field. One significant way to improve the contrast in MRI is to introduce contrast agents. MRI contrast agents are a unique class of pharmaceuticals that enhance the image contrast between normal and diseased tissues and indicate the status of organ function or blood flow after administration by increasing the relaxation rates of water protons in tissue in which the agent accumulates [3,4]. According to the magnetic behavior, current MRI contrast agents can be categorized into two broad groups including paramagnetic metal chelates mostly used as the longitudinal (or spin-lattice) relaxation time T 1 -agents and superparamagnetic iron oxide particles usually used as the transverse (or spin-spin) relaxation time T 2 -agents [5][6][7]. Other paramagnetic substances with odd numbers of valence electrons, for example, organic free radicals such as nitroxides, have lower magnetic moments and have thus received less attention as MRI contrast agents [8,9].

Polyaspartamide spin probes containing isoindoline nitroxide and porphyrin groups

“…These new contrast agents enhanced MRI so as to emerge as a promising technique for the detection, diagnosis, and characterization of cancer. 22–24…”

“…The polyaspartamide isoindoline nitroxides retained similar electrochemical properties and redox reaction mechanisms as the parent nitroxides. [22][23][24] Some porphyrins and their metal complexes play important roles in MRI, photodynamic therapy (PDT), anticancer drugs, and fluorescence imaging because of their preferential selective uptake and retention by tumor tissues. Therefore, the water-soluble 5-(4′-aminophenyl)-10,15,20-tris(4′-sulfonatophenyl) porphyrin, trisodium salt-poly[α,β-N-(2hydroxyethyl)-l-aspartamide]-5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl is considered to be a novel potential spin probe for electron paramagnetic resonance.…”

“…1-3 However, the naturally occurring paramagnetic species amenable for EPRI in the body are below the detection limits and most possess a short half-life. [22][23][24] Some porphyrins and their metal complexes play important roles in MRI, photodynamic therapy (PDT), anticancer drugs, and fluorescence imaging because of their preferential selective uptake and retention by tumor tissues. 4,5 Due to their redox-and radical-trapping properties, nitroxides are extensively used as EPR spin labels for proteins, enzymes, nucleotides, and other biological systems.…”

Porphyrin-containing polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents

“…One important way to improve the contrast in MRI is to introduce contrast agents. MRI contrast agents are a unique class of pharmaceuticals that enhance the image contrast between normal and diseased tissue and indicate the status of organ function or blood flow after administration by increasing the relaxation rates of water protons in tissue in which the agent accumulates Yan et al, 2007bYan et al, , 2008cYan et al, , 2010a.…”

“…Compared with the low molecular weight metal complex Gd-DTPA, macromolecular contrast agents may show more effective relaxation rates and prolonged intravascular retention due to their bulky molecular volume (Yan et al, 2007b(Yan et al, , 2010a. They offer the opportunity for measuring changes in regional blood volume and can be used clinically as the blood pool contrast agents in MRI and magnetic resonance angiography (MRA).…”