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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Aime S, Botta M, Ermondi G (1992) Nmr-study of solution structures and dynamics of lanthanide(III) complexes of dota. Inorg Chem 31:4291–4299
Aime S, Botta M, Fasano M, Geninatti Crich S, Terreno E (1996a) Gd(III) complexes as contrast agents for magnetic resonance imaging: a proton relaxation enhancement study of the interaction with human serum albumin. J Biol Inorg Chem 1:312–319
Aime S, Botta M, Fasano M, Terreno E, Kinchesh P, Calabi L, Paleari L (1996b) A new ytterbium chelate as contrast agent in chemical shift imaging and temperature sensitive probe for MR spectroscopy. Magn Res Med 35:648–651
Aime S, Botta M, Fasano M, Terreno E (1998) Lanthanide(III) chelates for NMR biomedical applications. Chem Soc Rev 27:19–29
Aime S, Barge A, Bruce J, Botta M, Howard JAK, Moloney JM, Parker D, de Sousa AS, Woods M (1999a) NMR, relaxometric, and structural studies of the hydration and exchange dynamics of cationic lanthanide complexes of macrocyclic tetraamide ligands. J Am Chem Soc 121:5762–5771
Aime S, Botta M, Fasano M, Terreno E (1999b) Prototropic and water-exchange processes in aqueous solutions of Gd(III) chelates. Acc Chem Res 32:941–949
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 4:766–774
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 193–241
Aime S, Cabella C, Colombatto S, Crich SG, Gianolio E, Maggioni F (2002 a) Insights into the use of paramagnetic Gd(III) complexes in MR-molecular imaging investigations. J Magn Reson Imaging 16:394–406
Aime S, Frullano L, Geninatti Crich S (2002 b) Compartmentalization of a gadolinium complex in the apoferritin cavity: A route to obtain high relaxivity contrast agents for magnetic resonance imaging. Angew Chemie Int Ed 41:1017–1019
Allen MJ, Meade TJ (2003) Synthesis and visualization of a membrane-permeable MRI contrast agent. J Biol Inorg Chem 8:746–750
Banci L, Bertini I, Luchinat C (1991) Nuclear and electronic relaxation. VCH, Weinheim, pp 91–122
Bhorade R, Weissleder R, Nakakoshi T, Moore A, Tung CH (2000) Macrocyclic chelators with paramagnetic cations are internalized into mammalian cells via a HIV-tat derived membrane translocation peptide. Bioconjugate Chem 11:301–305
Bhujwalla ZM, Artemov D, Mori N, Ravi R (2003) Magnetic resonance molecular imaging of the HER-2/neu receptor. Cancer Res 63:2723–2727
Botta M (2000) Second coordination sphere water molecules and relaxivity of gadolinium(III) complexes: implications for MRI contrast agents. Eur J Inorg Chem 3:399–407
Caravan P, Ellison JJ, McMurry TJ, Lauffer RB (1999) Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev 99:2293–2352
Carter D, Ho JX (1994) Structure of serum-albumin. Adv Prot Chem 45: 153–203
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 75–82
Dwek RA (1973) Nuclear magnetic resonance in biochemistry, applications to enzyme systems, Clarendon Press, Oxford, pp 174–283
Heckl S, Pipkorn R, Waldeck W, Spring H, Jenne J, von der Lieth CW, Corban-Wilhelm H, Debus J, Braun K (2003) Intracellular visualization of prostate cancer using magnetic resonance imaging. Cancer Res 63:4766–4772
Kobayashi H, Brechbiel MW (2003) Dendrimer-based macromolecular MRI contrast agents: characteristics and application. Mol Imaging 2:1–10
Merbach AE, Tóth E (2001) The chemistry of contrast agents in medical magnetic resonance imaging. Wiley, Chichester
Osterloh K, Aisen P (1989) Pathways in the binding and uptake of ferritin by hepatocytes. Biochem Biophys Acta 1011:40–45
Padhani AR (2002) Dynamic contrast-enhanced MRI in clinical oncology: current status and future directions. J Magn Res 16:407–422
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 118:9333–9346
Rinck PA (2003) Magnetic resonance in medicine. ABW Wissenschaftsverlag, Berlin
Sipkins DA, Cheresh DA, Kazemi MR, Nevin LM, Bednarski MD, Li KCP (1998) Detection of tumor angiogenesis in vivo by alpha(v)beta(3-targeted magnetic resonance imaging. Nat Med 4:623–626
Weissleder R, Mahmood U (2001) Molecular imaging. Radiology 219:316–333
Weissleder R, Bogdanov A, Matuszewski L, Bremer C, Petrovski A (2002) Oligomerization of paramagnetic substrates result in signal amplification and can be used for MR imaging of molecular targets. Mol Imag 1:16–23
Wiener EC, Konda S, Shadron A, Brechbiel M, Gansow O (1997) Targeting dendrimer-chelates to tumors and tumor cells expressing the high-affinity folate receptor. Invest Radiol 32:748–754
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 63:5838–5843
Young IR (2000) Methods in biomedical magnetic resonance imaging and spectroscopy. Wiley, Chichester
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Aime, S., Barge, A., Gianolio, E., Pagliarin, R., Silengo, L., Tei, L. (2005). High Relaxivity Contrast Agents for MRI and Molecular Imaging. In: Bogdanov, A.A., Licha, K. (eds) Molecular Imaging. Ernst Schering Research Foundation Workshop, vol 49. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26809-X_6
Download citation
DOI: https://doi.org/10.1007/3-540-26809-X_6
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-21021-4
Online ISBN: 978-3-540-26809-3
eBook Packages: MedicineMedicine (R0)