Synthetic approaches to heterocyclic ligands for Gd-based MRI contrast agents

Abstract

Magnetic Resonance Imaging (MRI) methods are currently used in the clinic for the non invasive detection and characterization of a wide variety of pathologies. Increases in the diagnostic efficiency of MRI have been helped by both the design of dedicated MR sequences revealing specific aspects of the pathology and by the development of more sensitive and selective Contrast Agents (CAs), capable of more precisely delineating the borderline regions. In the present review we focus on the synthetic strategies used to obtain MRI CAs containing heterocyclic rings.

Figure 1

Some useful probes for PET, SPECT, X-Ray and Optical Imaging.

Figure 2

Gd(III) complexes commonly used in clinical practice.

Scheme 1

Optically active acyclic ligands derived from (S)-aspartic acid and (S)-histidine.

Scheme 2

Pyridine derivatives 12a-c based on an ethylendiamine chelate.

Scheme 3.

Figure 3

Chelating ligands for Gd(III) with Bi and bis-pyrazole skeleton.

Scheme 4

Gd(III) Chelators from 4-chloromethylpyrazoles.

Scheme 5.

Scheme 6.

Scheme 7

Dtpa analogues derived from piperidine and azepane.

Scheme 8.

Scheme 9.

Figure 4.

Scheme 10.

Scheme 11

Dtpa bis-indole derivative.

Scheme 12

Gd(III)-40 recognizing and reversibly binding to the sialic acid residues.

Scheme 13

Synthesis of DPDP as chelating ligand for Mn(II).

Scheme 14

Two synthetic strategies to prepare 51.

Scheme 15.

Scheme 16

Dendrimeric chelating ligand derived from hydroxypyridonate.

Figure 5

Cyclen derivatives used to synthesize the most useful macrocyclic CAs.

Scheme 17.

Scheme 18

Pyridylmethyltetraamides as pH responsive CAs.

Scheme 19

ATP-conjugated DO3A 67 which its Gd(III)-complex showing pH dependence relaxivity.

Scheme 20.

Figure 6

Scheme 21.

Scheme 22.

Scheme 23.

Scheme 24

Lipophilic macromolecular chelators of lanthanide ions 79.

Figure 7

Multinuclear complex based on 5,6-dihydro-1,10-phenanthrolin-5-yl-DO3A.

Scheme 25.