Abstract
The application of magnetic resonance imaging (MRI) is often limited by low magnetic relaxivity of currently used contrast agents. This problem can be addressed by developing more sensitive contrast agents by synthesizing new types of metal complex or metallic nanoparticles. Protein cage has been used as a template in biological synthesis of magnetic nanoparticles. The magnetic nanoparticle-protein cage composites have been reported to have high magnetic relaxivity, which implies their potential application as an MRI contrast agent. The magnetic relaxivity is determined by measuring longitudinal and transverse magnetic relaxivities of the potential agent. The commonly performed techniques are field-cycling NMR relaxometry (also known as variable field relaxometry or nuclear magnetic relaxation dispersion (NMRD) profiling) and in vitro or in vivo MRI relaxometry. Here, we describe techniques for the synthesis of nanoparticle-protein cage composite and determination of their magnetic relaxivities by in vitro MR image acquisition and data processing. In this method, longitudinal and transverse relaxivities are calculated by measuring relaxation rates of water hydrogen nuclei at different nanoparticle-protein cage composite concentrations.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Caravan P, Ellison JJ, McMurry TJ, Lauffer RL (1999) Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev 99:2293–2352
Bulte JW, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17:484–499
Lu J, Ma S, Sun J, Xia C, Liu C, Wang Z, Zhao X, Gao F, Gong Q, Song B, Shuai X, Ai H, Gu Z (2009) Manganese ferrite nanoparticle micellar nanocomposites as MRI contrast agent for liver imaging. Biomaterials 30:2919–2928
Weissleder R, Mahmood U (2001) Molecular imaging. Radiology 219:316–333
Kubicek V, Toth E (2009) Design and function of metal complexes as contrast agents in MRI. Adv Inorg Chem 61:63–129
Reimer P, Balzer T (2003) Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development, and applications. Eur Radiol 3:1266–1276
Bleicher AG, Kanal E (2008) Assessment of adverse reaction rates to a newly approved MRI contrast agent: review of 23,553 administrations of gadobenate dimeglumine. Am J Roentgenol 191:W307–W311
Wang YXJ (2011) Super paramagnetic iron oxide based MRI contrast agents: current status of clinical applications. Quant Imaging Med Surg 1:35–40
Yalappu MM, Othman SF, Curtis ET, Gupta BK, Jaggi M, Chauhan SC (2010) Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy. Biomaterials 32:1890–1905
Huang J, Zhong X, Wang L, Yang L, Mao H (2012) Improving the magnetic resonance imaging contrast and detection methods with engineered magnetic nanoparticles. Theranostics 2:86–102
Koylu MZ, Asubay S, Yilmaz A (2009) Determination of proton relaxivities of Mn(II), Cu(II) and Cr(III) added to solutions of serum proteins. Molecules 14:1537–1545
Yang JJ, Yang J, Wei L, Zurkiya O, Yang W, Li S, Zou J, Maniccia AL, Mao H, Zhao F, Malchow R, Zhao S, Johnson J, Hu X, Krogstad E, Liu ZR (2008) Rational design of protein-based MRI contrast agents. J Am Chem Soc 130:9260–9267
Galvez N, Fernandez B, Valero E, Sanchez P, Cuesta R, Dominguez-Vera JM (2008) Apoferritin as a nanoreactor for preparing metallic nanoparticles. Comp Rendus Chim 11:1207–1212
Yoshizawa K, Iwahori K, Sugimoto K, Yamashita I (2006) Fabrication of gold sulfide nanoparticles using the protein cage of apoferritin. Chem Lett 35:1192–1193
Aime S, Frullano L, Crich SG (2002) Compartmentalization of a gadolinium complex in the apoferritin cavity: a route to obtain high relaxivity contrast agents for magnetic resonance imaging. Angew Chem Int Ed 41:1017–1019
Crich SG, Bussolati B, Tei L, Grange C, Esposito G, Lanzardo S, Camussi G, Aime S (2006) Magnetic resonance visualization of tumor angiogenesis by targeting neural cell adhesion molecules with the highly sensitive gadolinium-loaded apoferritin probe. Cancer Res 66:9196–9201
Sanchez P, Valero E, Galvez N, Dominguez-Vera JM, Marinone M, Poletti G, Corti M, Lascialfari A (2009) MRI relaxation properties of water-soluble apoferritin-encapsulated gadolinium oxide-hydroxide nanoparticles. Dalton Trans 5:800–804
Uchida M, Terashima M, Cunningham CH, Suzuki Y, Willitis DA, Yang PC, Tsao PS, McConnell MV, Young MJ, Douglas T (2008) A human ferritin iron oxide nano-composite magnetic resonance contrast agent. Magn Reson Med 60:1073–1081
Sana B, Johnson E, Sheah K, Poh CL, Lim S (2010) Iron based ferritin nanocore as a contrast agent. Biointerphases 5:AF48–AF52
Sana B, Poh CL, Lim S (2012) A manganese-ferritin nanocomposites as an ultrasensitive T2 contrast agent. Chem Commun 48:862–864
Sana B, Calista M, Lim S (2012) Protein cage assisted metal-protein nanocomposite synthesis: optimization of loading conditions. AIP Conf Proc 1502:82–96
Qiu H, Dong X, Sana B, Peng T, Parapelle D, Chen P, Lim S (2013) Ferritin-templated synthesis and self-assembly of Pt nanoparticles on monolithic porous graphene network for electrocatalysis in fuel cell. ACS Appl Mater Interfaces 5:782–787
Acknowledgment
The authors thank Dr. Cher Heng Tan at Tan Tock Seng Hospital, Singapore, for technical advices on magnetic resonance imaging. The work is supported by Singapore National Medical Research Council New Investigator Grant (NMRC/NIG/1073/2012)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Sana, B., Lim, S. (2015). Determining the Relaxivity Values of Protein Cage-Templated Nanoparticles Using Magnetic Resonance Imaging. In: Orner, B. (eds) Protein Cages. Methods in Molecular Biology, vol 1252. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2131-7_4
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2131-7_4
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2130-0
Online ISBN: 978-1-4939-2131-7
eBook Packages: Springer Protocols