Recent Advances in Bifunctional Paramagnetic Chelates for MRI

Abstract

Magnetic resonance imaging (MRI) is a non‐invasive diagnostic modality routinely employed in modern clinical medicine to collect images of the internal organs of the human body. Contrast agents (CA) are usually administered to patients to improve the sensitivity of this technique and nowadays these agents are gadolinium complexes. Bifunctional chelating agents (BFCAs) are dual molecules containing a multidentate ligand, able to strongly coordinate a metal ion, and a reactive moiety for conjugation purposes. With BFCAs an easy labelling of biomolecules or vectors with paramagnetic ions is possible, allowing the in vivo MRI visualization of diseases at cellular or molecular level.

TRASUTA: The Effect of the Structural Rigidity of a Mesocyclic AAZTA-like Chelating Agent on the Thermodynamic, Kinetic, and Structural Properties of Some Divalent Metal and Ga3+ Complexes

“…AAZTA 11 can be easily obtained from inexpensive starting materials, and its complexes with several divalent and trivalent metal ions show good thermodynamic stability associated with fast formation kinetics. 12−15 Owing to these valuable features, several AAZTA-like bifunctional chelating agents 16,17 were synthesized, conjugated to diagnostic-relevant biomolecules, and labeled with metal ions to give a vast array of diagnostic imaging probes. 18−25 Among them, 68 Ga 3+ complexes recently gained a widespread interest as PET contrast agents, culminated in the approval for clinical use by FDA and EMA of 68 Ga-edotreotide ([ 68 Ga]-Ga-DOTATOC) to detect somatostatin receptorpositive neuroendocrine tumors.…”

“…A good compromise between fast complexation kinetics and thermodynamic stability has been achieved with AAZTA, a heptadentate mesocyclic polyaminocarboxylic chelating agent, as well as with its hexadentate derivative DATA m (Figure ). AAZTA can be easily obtained from inexpensive starting materials, and its complexes with several divalent and trivalent metal ions show good thermodynamic stability associated with fast formation kinetics. − Owing to these valuable features, several AAZTA-like bifunctional chelating agents , were synthesized, conjugated to diagnostic-relevant biomolecules, and labeled with metal ions to give a vast array of diagnostic imaging probes. − …”

Solid phase synthesis in the development of magnetic resonance imaging probes

“…Consequently, the increased complexity of the probes can often lead to more challenging synthesis and arduous purification procedures. [13][14][15] Alternative synthetic methods such as solid phase synthesis (SPS) offer specific advantages over standard solution phase techniques, which can be employed to circumvent these issues and enable more 'complex' and specific derivatives to be developed. Indeed various radiopharmaceuticals, [16][17][18][19][20][21][22][23][24][25][26][27] lanthanide luminescent polyaminopolycarboxylate complexes [28][29][30][31][32][33][34][35][36] and other peptidemetal complex conjugates have been developed using SPS protocols.…”