Abstract
Molecular magnetic resonance imaging (MRI) provides information non-invasively at cellular and molecular levels, for both early diagnosis and monitoring therapeutic follow-up. This imaging technique requires the development of a new class of contrast agents, which signal changes (typically becomes enhanced) when in presence of the cellular or molecular process to be evaluated. Even if molecular MRI has had a prominent role in the advances in medicine over the past two decades, the large majority of the developed probes to date are still in preclinical level, or eventually in phase I or II clinical trials. The development of novel imaging probes is an emergent active research domain. This review focuses on gadolinium-based specific-targeted contrast agents, providing rational design considerations and examples of the strategies recently reported in the literature.
Highlights
Molecular imaging offers the capacity of detecting and following-up events of processes happening at cellular and molecular levels that are signature of early stages of a disease.Such medical exams require the use of a contrast agent (CA) that is specific to the event or process to detect, or which signal depends on the later.Molecular magnetic resonance imaging (MRI) is a powerful non-invasive imaging technique which takes advantage of a very high spatial and temporal resolution and can provide detailed molecular/cellular information when combined with a contrast agent
The use of the AAZTA chelate unit instead of the DTPA brings an extra water molecule to the inner sphere (q = 2 for Gd-AAZTA), which justifies the higher relaxivity of the complex Gd-B25716/1 in PBS: the r1 is 13.0 mM−1 ·s−1 for Gd-B25716/1, 1.5-fold higher when compared with 8.6 mM−1 ·s−1 for B22956/1
Small molecule-based CAs are mostly based on derivatives of: (1) Pittsburgh compound B (PiB), a derivative of the thioflavin T which binds to fibrillar Aβ amyloid deposits in situ; (2) Curcumin; (3) Congo Red and (4) stilbene
Summary
Molecular imaging offers the capacity of detecting and following-up events of processes happening at cellular and molecular levels that are signature (biomarkers) of early stages of a disease. The CAs in clinical use are low molecular weight Gd3+ -based complexes (0.5–1 KDa) with one water molecule in the inner-sphere, which relaxivities range from 3 to 5 mM−1 ·s−1 at 1.5 or 3 T (clinical magnetic fields) When administered, these imaging probes will distribute within the organism without a specific target (except for Vasovist® ) and are able to give information on pathologies that result in changes in the vascular volume, perfusion and permeability of the tissues/organs. Estimations based on the parameters of the clinical CA available and the recommended injected dose for an MRI probe (0.1 mmol Gd3+ /kg), showed that to get a detectable signal enhancement, a minimum of 100 μM Gd3+ local concentration is needed. The rational design of novel generation of CA is in general accompanied by the optimization of the stability and relaxivity features of the Gd3+ complex unit
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
