High Relaxivity Contrast Agents for MRI and Molecular Imaging
6.5 Concluding Remarks
Gd(III) chelates have played an important role in the development of clinical applications of MRI technique by adding relevant physiological information to the superb anatomical resolution attainable with this imaging modality.
More is still expected with the currently available contrast agents, especially in the field of dynamic contrast enhancement protocols reporting on changes of the vascular permeability associated with the staging and therapeutic follow-up of important pathologies. However, the major challenges are in the emerging field of molecular imaging where the competition with other imaging modalities can be very tight. Targeting of thrombi and atherosclerotic plaques by peptides functionalized with Gd(III) chelates appears to be the next goal for industrial research. The possibility of identifying and characterizing vulnerable plaques will certainly represent an important task. Clearly, there is a need for new ideas for enhancing the attainable relaxivity at higher fields as the 3-T indication for clinical imagers seems to be quite established. Moreover, it will be necessary to improve the efficiency of the available delivery systems and, possibly, to exploit suitable amplification procedures in order to reach the sensitivity required for the visualization of target molecules present at low concentrations.
The results herein surveyed show that there are several routes for cell entrapment of paramagnetic Gd-agents at concentrations sufficient for MRI visualization. The huge work carried out in a number of laboratories in the last two decades for the development of Gd-based MRI contrast agents provides an excellent platform for designing a new generation of probes for molecular imaging applications. Though one should not underestimate the difficulties that will arise when going from in vitro experiments to in vivo animal studies, we think that the available results suggest that Gd-chelates will have an important role in the armory of imaging probes for cellular and molecular imaging applications.
KeywordsContrast Agent Magnetic Resonance Imaging Contrast Agent Relaxation Enhancement Water Exchange Rate Exchange Lifetime
Unable to display preview. Download preview PDF.
- Aime S, Chiaussa M, Digilio G, Gianolio E, Terreno E (1999 c) Contrast agents for magnetic resonance angiographic applications: H-l and O-17 NMR relaxometric investigations on two gadolinium(III) DTPA-like chelates endowed with high binding affinity to human serum albumin. J Biol Inorg Chem 4:766–774PubMedCrossRefGoogle Scholar
- Aime S, Fasano M, Terreno E, Botta M (2001) In: Merbach AE, Tóth E (eds) The chemistry of contrast agents in medical magnetic resonance imaging. Wiley, Chichester, pp 193–241Google Scholar
- Banci L, Bertini I, Luchinat C (1991) Nuclear and electronic relaxation. VCH, Weinheim, pp 91–122Google Scholar
- Di Bari L, Pintacuda G, Salvadori P (2000) Solution equilibria in YbDOT-MA, a chiral analogue of one of the most successful contrast agents for MRI, GdDOTA. Eur J Inorg Chem 75–82Google Scholar
- Dwek RA (1973) Nuclear magnetic resonance in biochemistry, applications to enzyme systems, Clarendon Press, Oxford, pp 174–283Google Scholar
- Merbach AE, Tóth E (2001) The chemistry of contrast agents in medical magnetic resonance imaging. Wiley, ChichesterGoogle Scholar
- Powell DH, Ni Dhubhghaill OM, Pubanz D, Helm L, Lebedev HS, Schlaep-fer W, Merbach AE (1996) Structural and dynamic parameters obtained from O-17 NMR, EPR, and NMRD studies of monomeric and dimeric Gd3+ complexes of interest in magnetic resonance imaging: an integrated and theoretically self consistent approach. J Am Chem Soc 118:9333–9346CrossRefGoogle Scholar
- Rinck PA (2003) Magnetic resonance in medicine. ABW Wissenschaftsverlag, BerlinGoogle Scholar
- Winter PM, Caruthers SD, Kassner A, Harris TD, Chinen LK, Allen JS, Lacy EK, Zhang HY, Robertson JD, Wickline SA, Lanza GM (2003) Molecular imaging of angiogenesis in nascent vx-2 rabbit tumors using a novel alpha(v)beta(3)-targeted nanoparticle and 1.5 tesla magnetic resonance imaging. Cancer Res 63:5838–5843PubMedGoogle Scholar
- Young IR (2000) Methods in biomedical magnetic resonance imaging and spectroscopy. Wiley, ChichesterGoogle Scholar