Quantitative cardiovascular magnetic resonance for molecular imaging

Cardiovascular magnetic resonance (CMR) molecular imaging aims to identify and map the expression of important biomarkers on a cellular scale utilizing contrast agents that are specifically targeted to the biochemical signatures of disease and are capable of generating sufficient image contrast. In some cases, the contrast agents may be designed to carry a drug payload or to be sensitive to important physiological factors, such as pH, temperature or oxygenation. In this review, examples will be presented that utilize a number of different molecular imaging quantification techniques, including measuring signal changes, calculating the area of contrast enhancement, mapping relaxation time changes or direct detection of contrast agents through multi-nuclear imaging or spectroscopy. The clinical application of CMR molecular imaging could offer far reaching benefits to patient populations, including early detection of therapeutic response, localizing ruptured atherosclerotic plaques, stratifying patients based on biochemical disease markers, tissue-specific drug delivery, confirmation and quantification of end-organ drug uptake, and noninvasive monitoring of disease recurrence. Eventually, such agents may play a leading role in reducing the human burden of cardiovascular disease, by providing early diagnosis, noninvasive monitoring and effective therapy with reduced side effects

Towards highly efficient and selective contrast agents for MRI

Abstract not availableApplied Science

Contrast agents for magnetic resonance imaging: A novel route to enhanced relaxivities based on the interaction of a Gd-III chelate with poly-beta-cyclodextrins

This study proposes a novel route to improved contrast agents for magnetic resonance imaging (MRI) applications based on the formation of a non-covalent adduct between a paramagnetic complex and an exogeneous macromolecule. For this purpose a 12-membered pyridine-containing triacetate macrocyclic ligand with a p-bromo-benzyloxy substituent on the pyridine moiety was synthesized. The Gd-III complex containing this ligand shows a relaxivity of 8.25 mM(-1)s(-1) at 20 MHz and 25 degrees C The hydrophobic p-bromo-benzyloxy moiety promotes the interaction of the chelate with human serum albumin (HSA) (K-a = 4 x 10(2) M-1) and with beta-cyclodextrin (K-a = 8 x 10(2) M-1). Upon replacing beta-cyclodextrin with a poly-beta-cyclodextrin substrate (MW = ca. 6000 Da) a further relaxation enhancement is detected as a consequence of the increased molecular size of the resulting inclusion compound. In a typical experiment in blood serum, the observed relaxivity is 32 mM(-1) s(-1) (20 MHz, 25 degrees C) when the concentrations are as follows: Gd-III chelate 1 mM, poly-beta-cyclodextrin 10 mM, HSA 0.58 mM. Under these conditions the Gd-III chelate is mainly present as an inclusion compound with the poly-beta-CD. This finding suggests a potential use for such a Gd-III chelate/poly-beta-CD system in MR angiographic application

Contrast agents for magnetic resonance imaging: A novel route to enhanced relaxivities based on the interaction of a Gd-III chelate with poly-beta-cyclodextrins

This study proposes a novel route to improved contrast agents for magnetic resonance imaging (MRI) applications based on the formation of a non-covalent adduct between a paramagnetic complex and an exogeneous macromolecule. For this purpose a 12-membered pyridine-containing triacetate macrocyclic ligand with a p-bromo-benzyloxy substituent on the pyridine moiety was synthesized. The Gd-III complex containing this ligand shows a relaxivity of 8.25 mM(-1)s(-1) at 20 MHz and 25 degrees C The hydrophobic p-bromo-benzyloxy moiety promotes the interaction of the chelate with human serum albumin (HSA) (K-a = 4 x 10(2) M-1) and with beta-cyclodextrin (K-a = 8 x 10(2) M-1). Upon replacing beta-cyclodextrin with a poly-beta-cyclodextrin substrate (MW = ca. 6000 Da) a further relaxation enhancement is detected as a consequence of the increased molecular size of the resulting inclusion compound. In a typical experiment in blood serum, the observed relaxivity is 32 mM(-1) s(-1) (20 MHz, 25 degrees C) when the concentrations are as follows: Gd-III chelate 1 mM, poly-beta-cyclodextrin 10 mM, HSA 0.58 mM. Under these conditions the Gd-III chelate is mainly present as an inclusion compound with the poly-beta-CD. This finding suggests a potential use for such a Gd-III chelate/poly-beta-CD system in MR angiographic applications

[GdPCP2A(H2O)(2)](-): A paramagnetic contrast agent designed for improved applications in magnetic resonance imaging

A novel ligand based on a pyridine-containing macrocycle bearing two acetic and one methylenephosphonic arms (PCP2A) has been synthesized. An efficient synthesis of PCP2A is based on the macrocyclization reaction between 2,6-bis(chloromethyl)pyridine and a 1,4,7-triazaheptane derivative bearing a methylenephosphonate group on N-4. The Gd(III) complex of PCP2A displays characteristic properties which make it a very promising contrast agent for improved applications in magnetic resonance imaging. In fact it shows (i) a very high stability constant (log K-GdPCP2A = 23.4) which should guarantee against the in vivo release of toxic free Gd(III) ions and free ligand molecules and (ii) a relaxivity that is about 2 times higher than the values reported for contrast agents currently used in the clinical practice. Its high relaxivity is the result of the presence of two water molecules in the inner coordination sphere and a significant contribution from water molecule(s) hydrogen bonded to the phosphonate group. Moreover, the inner sphere water molecules are involved in an exchange with the bulk water which is relatively fast. This property is important for the attainment of an even higher relaxivity once the molecular reorientation rate of the [GdPCP2A(H2O)(2)](-) moiety is lengthened by means of conjugation to a macromolecular substrate