Skip to main content

Designing Calcium-Binding Proteins for Molecular MR Imaging

  • Protocol
  • First Online:
Calcium-Binding Proteins of the EF-Hand Superfamily

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1929))

Abstract

Early diagnosis, noninvasive detection, and staging of various diseases, remain one of the major clinical barriers to effective medical treatment and prevention of disease progression toward major clinical consequences. Molecular imaging technologies play an indispensable role in the clinical field in overcoming these major barriers. The increasing application of imaging techniques and agents in early detection of different diseases such as cancer has resulted in improved treatment response and clinical patient management. In this chapter we will first introduce criteria for the design and engineering of calcium-binding protein (CaBP) parvalbumin as a protein Gd-MRI contrast agent (ProCA) with unprecedented metal selectivity for Gd3+ over physiological metal ions. We will then discuss the further development of targeted MRI contrast agent for molecular imaging of PSMA biomarker for early detection of prostate cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Tyszka JM, Fraser SE, Jacobs RE (2005) Magnetic resonance microscopy: recent advances and applications. Curr Opin Biotechnol 16(1):93–99. https://doi.org/10.1016/j.copbio.2004.11.004

    Article  CAS  PubMed  Google Scholar 

  2. Lippard SJ (2006) The inorganic side of chemical biology. Nat Chem Biol 2(10):504–507. https://doi.org/10.1038/nchembio1006-504

    Article  CAS  PubMed  Google Scholar 

  3. Lauffer RB, Vincent AC, Padmanabhan S, Villringer A, Saini S, Elmaleh DR, Brady TJ (1987) Hepatobiliary MR contrast agents: 5-substituted iron-EHPG derivatives. Magn Reson Med 4(6):582–590

    Article  CAS  Google Scholar 

  4. Aime S, Barge A, Cabella C, Crich SG, Gianolio E (2004) Targeting cells with MR imaging probes based on paramagnetic Gd(III) chelates. Curr Pharm Biotechnol 5(6):509–518

    Article  CAS  Google Scholar 

  5. Burai L, Scopelliti R, Toth E (2002) EuII-cryptate with optimal water exchange and electronic relaxation: a synthon for potential pO2 responsive macromolecular MRI contrast agents. Chem Commun (Camb) 20:2366–2367

    Article  Google Scholar 

  6. Geraldes CF, Sherry AD, Cacheris WP, Kuan KT, Brown RD 3rd, Koenig SH, Spiller M (1988) Number of inner-sphere water molecules in Gd3+ and Eu3+ complexes of DTPA-amide and -ester conjugates. Magn Reson Med 8(2):191–199

    Article  CAS  Google Scholar 

  7. Caravan P (2006) Strategies for increasing the sensitivity of gadolinium based MRI contrast agents. Chem Soc Rev 35(6):512–523. https://doi.org/10.1039/b510982p

    Article  CAS  PubMed  Google Scholar 

  8. Weinmann HJ, Press WR, Gries H (1990) Tolerance of extracellular contrast agents for magnetic resonance imaging. Investig Radiol 25(Suppl 1):S49–S50

    Article  CAS  Google Scholar 

  9. Opsahl LR, Uzgiris EE, Vera DR (1995) Tumor imaging with a macromolecular paramagnetic contrast agent: gadopentetate dimeglumine-polylysine. Acad Radiol 2(9):762–767

    Article  CAS  Google Scholar 

  10. Langereis S, de Lussanet QG, van Genderen MH, Meijer EW, Beets-Tan RG, Griffioen AW, van Engelshoven JM, Backes WH (2006) Evaluation of Gd(III)DTPA-terminated poly(propylene imine) dendrimers as contrast agents for MR imaging. NMR Biomed 19(1):133–141. https://doi.org/10.1002/nbm.1015

    Article  CAS  PubMed  Google Scholar 

  11. Bryant LH Jr, Brechbiel MW, Wu C, Bulte JW, Herynek V, Frank JA (1999) Synthesis and relaxometry of high-generation (G = 5, 7, 9, and 10) PAMAM dendrimer-DOTA-gadolinium chelates. J Magn Reson Imaging 9(2):348–352

    Article  Google Scholar 

  12. Sirlin CB, Vera DR, Corbeil JA, Caballero MB, Buxton RB, Mattrey RF (2004) Gadolinium-DTPA-dextran: a macromolecular MR blood pool contrast agent. Acad Radiol 11(12):1361–1369. https://doi.org/10.1016/j.acra.2004.11.016

    Article  PubMed  Google Scholar 

  13. Lanza GM, Winter PM, Caruthers SD, Morawski AM, Schmieder AH, Crowder KC, Wickline SA (2004) Magnetic resonance molecular imaging with nanoparticles. J Nucl Cardiol 11(6):733–743

    Article  Google Scholar 

  14. Lanza GM, Winter P, Caruthers S, Schmeider A, Crowder K, Morawski A, Zhang H, Scott MJ, Wickline SA (2004) Novel paramagnetic contrast agents for molecular imaging and targeted drug delivery. Curr Pharm Biotechnol 5(6):495–507

    Article  CAS  Google Scholar 

  15. Anderson EA, Isaacman S, Peabody DS, Wang EY, Canary JW, Kirshenbaum K (2006) Viral nanoparticles donning a paramagnetic coat: conjugation of MRI contrast agents to the MS2 capsid. Nano Lett 6(6):1160–1164. https://doi.org/10.1021/nl060378g

    Article  CAS  PubMed  Google Scholar 

  16. Strijkers GJ, Mulder WJ, van Heeswijk RB, Frederik PM, Bomans P, Magusin PC, Nicolay K (2005) Relaxivity of liposomal paramagnetic MRI contrast agents. MAGMA 18(4):186–192. https://doi.org/10.1007/s10334-005-0111-y

    Article  CAS  PubMed  Google Scholar 

  17. Stosiek C, Garaschuk O, Holthoff K, Konnerth A (2003) In vivo two-photon calcium imaging of neuronal networks. Proc Natl Acad Sci U S A 100(12):7319–7324. https://doi.org/10.1073/pnas.1232232100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wallingford JB, Ewald AJ, Harland RM, Fraser SE (2001) Calcium signaling during convergent extension in Xenopus. Curr Biol 11(9):652–661

    Article  CAS  Google Scholar 

  19. Caravan P, Greenwood JM, Welch JT, Franklin SJ (2003) Gadolinium-binding helix-turn-helix peptides: DNA-dependent MRI contrast agents. Chem Commun (Camb) 20:2574–2575

    Article  Google Scholar 

  20. Kim Y, Welch JT, Lindstrom KM, Franklin SJ (2001) Chimeric HTH motifs based on EF-hands. J Biol Inorg Chem 6(2):173–181

    Article  Google Scholar 

  21. Atanasijevic T, Shusteff M, Fam P, Jasanoff A (2006) Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin. Proc Natl Acad Sci U S A 103(40):14707–14712. https://doi.org/10.1073/pnas.0606749103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Xue S, Yang H, Qiao J, Pu F, Jiang J, Hubbard K, Hekmatyar K, Langley J, Salarian M, Long RC, Bryant RG, Hu XP, Grossniklaus HE, Liu ZR, Yang JJ (2015) Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging. Proc Natl Acad Sci U S A 112(21):6607–6612. https://doi.org/10.1073/pnas.1423021112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pu F, Salarian M, Xue S, Qiao J, Feng J, Tan S, Patel A, Li X, Mamouni K, Hekmatyar K, Zou J, Wu D, Yang JJ (2016) Prostate-specific membrane antigen targeted protein contrast agents for molecular imaging of prostate cancer by MRI. Nanoscale 8(25):12668–12682. https://doi.org/10.1039/c5nr09071g

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pu F, Qiao J, Xue S, Yang H, Patel A, Wei L, Hekmatyar K, Salarian M, Grossniklaus HE, Liu ZR, Yang JJ (2015) GRPR-targeted protein contrast agents for molecular imaging of receptor expression in cancers by MRI. Sci Rep 5:16214. https://doi.org/10.1038/srep16214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Xue S, Qiao J, Jiang J, Hubbard K, White N, Wei L, Li S, Liu ZR, Yang JJ (2014) Design of ProCAs (protein-based Gd(3+) MRI contrast agents) with high dose efficiency and capability for molecular imaging of cancer biomarkers. Med Res Rev 34(5):1070–1099. https://doi.org/10.1002/med.21313

    Article  CAS  PubMed  Google Scholar 

  26. Qiao J, Xue S, Pu F, White N, Jiang J, Liu ZR, Yang JJ (2014) Molecular imaging of EGFR/HER2 cancer biomarkers by protein MRI contrast agents. J Biol Inorg Chem 19(2):259–270. https://doi.org/10.1007/s00775-013-1076-3

    Article  CAS  PubMed  Google Scholar 

  27. Li S, Jiang J, Zou J, Qiao J, Xue S, Wei L, Long R, Wang L, Castiblanco A, White N, Ngo J, Mao H, Liu ZR, Yang JJ (2012) PEGylation of protein-based MRI contrast agents improves relaxivities and biocompatibilities. J Inorg Biochem 107(1):111–118. https://doi.org/10.1016/j.jinorgbio.2011.11.004

    Article  CAS  PubMed  Google Scholar 

  28. Pu F, Xue S, Qiao J, Patel A, Yang JJ (2016) Towards the Molecular Imaging of Prostate Cancer Biomarkers Using Protein-based MRI Contrast Agents. Curr Protein Pept Sci 17(6):519–533

    Article  CAS  Google Scholar 

  29. Wang X, Kirberger M, Qiu F, Chen G, Yang JJ (2009) Towards predicting Ca2+−binding sites with different coordination numbers in proteins with atomic resolution. Proteins 75(4):787–798. https://doi.org/10.1002/prot.22285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kirberger M, Wang X, Deng H, Yang W, Chen G, Yang JJ (2008) Statistical analysis of structural characteristics of protein Ca2+− binding sites. J Biol Inorg Chem 13(7):1169–1181. https://doi.org/10.1007/s00775-008-0402-7

    Article  CAS  PubMed  Google Scholar 

  31. Wang X, Zhao K, Kirberger M, Wong H, Chen G, Yang JJ (2010) Analysis and prediction of calcium-binding pockets from apo-protein structures exhibiting calcium-induced localized conformational changes. Protein Sci 19(6):1180–1190. https://doi.org/10.1002/pro.394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhou Y, Yang W, Kirberger M, Lee HW, Ayalasomayajula G, Yang JJ (2006) Prediction of EF-hand calcium-binding proteins and analysis of bacterial EF-hand proteins. Proteins 65(3):643–655. https://doi.org/10.1002/prot.21139

    Article  CAS  PubMed  Google Scholar 

  33. Dees A, Zahl A, Puchta R, Hommes NJ, Heinemann FW, Ivanovic-Burmazovic I (2007) Water exchange on seven-coordinate Mn(II) complexes with macrocyclic pentadentate ligands: insight in the mechanism of Mn(II) SOD mimetics. Inorg Chem 46(7):2459–2470. https://doi.org/10.1021/ic061852o

    Article  CAS  PubMed  Google Scholar 

  34. Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260(6):3440–3450

    CAS  PubMed  Google Scholar 

  35. Sudnick DR, Horrocks WD Jr (1979) Lanthanide ion probes of structure in biology. Environmentally sensitive fine structure in laser-induced terbium(III) luminescence. Biochim Biophys Acta 578(1):135–144

    Article  CAS  Google Scholar 

  36. Caravan P, Ellison JJ, McMurry TJ, Lauffer RB (1999) Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev 99(9):2293–2352

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We appreciate the critical review by Dr. Michael Kirberger and previous works by Drs. Fan Pu, Jingjuan Qiao, and Jie Jiang. This work is supported in part by grants R42 CA183376, R41CA177034, R41AA112713, EB007268, 1R01GM081749 from National Health Institute to Jenny J. Yang. This work was also supported by the Molecular Basis of Disease (MBD) Fellowship to M. Salarian and Center for Diagnostics and Therapeutics (CDT) Fellowship to O. Y. Ibhagui.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jenny J. Yang .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Salarian, M., Xue, S., Ibhagui, O.Y., Yang, J.J. (2019). Designing Calcium-Binding Proteins for Molecular MR Imaging. In: Heizmann, C. (eds) Calcium-Binding Proteins of the EF-Hand Superfamily. Methods in Molecular Biology, vol 1929. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9030-6_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9030-6_8

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9029-0

  • Online ISBN: 978-1-4939-9030-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics