Water-soluble lipophilic MR contrast agents for cell membrane labeling

JBIC Journal of Biological Inorganic Chemistry volume 20, pages971–977(2015)Cite this article

Abstract

Long-term cell tracking using MR imaging necessitates the development of contrast agents that both label and are retained by cells. One promising strategy for long-term cell labeling is the development of lipophilic Gd(III)-based contrast agents that anchor into the cell membrane. We have previously reported the efficacy of monomeric and multimeric lipophilic agents and showed that the monomeric agents have improved labeling and contrast enhancement of cell populations. Here, we report on the synthesis, characterization, and in vitro testing of a series of monomeric lipophilic contrast agents with varied alkyl chain compositions. We show that these agents disperse in water, localize to the cell membrane, and label HeLa and MCF7 cells effectively. Additionally, these agents have up to tenfold improved retention in cells compared to clinically available ProHance®.

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References

  1. 1.

    Valone FH, Small E, MacKenzie M, Burch P, Lacy M, Peshwa MV, Laus R (2001) Cancer J 7:S53–S61

    PubMed  Google Scholar 

  2. 2.

    Fernandez-Aviles F, San Roman JA, Garcia-Frade J, Fernandez ME, Penarrubia MJ, de la Fuente L, Gomez-Bueno M, Cantalapiedra A, Fernandez J, Gutierrez O, Sanchez PL, Hernandez C, Sanz R, Garcia-Sancho J, Sanchez A (2004) Circ Res 95;742–748

  3. 3.

    Semsarian C (2002) Intern Med J 32:259–265

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Petit-Zeman S (2001) Nat Biotechnol 19:201–206

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Marr RA, Thomas RM, Peterson DA (2010) Future Neurol 5:527–541

    PubMed Central  Article  PubMed  Google Scholar 

  6. 6.

    Webb GA (2006) Modern magnetic resonance. Springer, Dordrecht

    Google Scholar 

  7. 7.

    Rogers WJ, Meyer CH, Kramer CM (2006) Nat Clin Pract Card 3:554–562

    Article  CAS  Google Scholar 

  8. 8.

    Caravan P, Ellison JJ, McMurry TJ, Lauffer RB (1999) Chem Rev 99:2293–2352

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Merbach AE, Tóth E (2001) The chemistry of contrast agents in medical magnetic resonance imaging. Wiley, Chichester

    Google Scholar 

  10. 10.

    Daldrup-Link HE, Rudelius M, Metz S, Piontek G, Pichler B, Settles M, Heinzmann U, Schlegel J, Oostendorp RAJ, Rummeny EJ (2004) Eur J Nucl Med Mol Imaging 31:1312–1321

    Article  PubMed  Google Scholar 

  11. 11.

    Allen MJ, MacRenaris KW, Venkatasubramanian PN, Meade TJ (2004) Chem Biol 11:301–307

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Endres PJ, MacRenaris KW, Vogt S, Meade TJ (2008) Bioconjugate Chem 19:2049–2059

    Article  CAS  Google Scholar 

  13. 13.

    Wunderbaldinger P, Josephson L, Weissleder R (2002) Bioconjugate Chem 13:264–268

    Article  CAS  Google Scholar 

  14. 14.

    Modo M, Cash D, Mellodew K, Williams SCR, Fraser SE, Meade TJ, Price J, Hodges H (2002) Neuroimage 17:803–811

    Article  PubMed  Google Scholar 

  15. 15.

    Modo M, Mellodew K, Cash D, Fraser SE, Meade TJ, Price J, Williams SCR (2004) Neuroimage 21:311–317

    Article  PubMed  Google Scholar 

  16. 16.

    Liu Y, He ZJ, Xu B, Wu QZ, Liu G, Zhu HY, Zhong Q, Deng DY, Ai H, Yue Q, Wei Y, Jun S, Zhou GQ, Gong QY (2011) Brain Res 1391:24–35

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Hsiao JK, Tsai CP, Chung TH, Hung Y, Yao M, Liu HM, Mou CY, Yang CS, Chen YC, Huang DM (2008) Small 4:1445–1452

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Terreno E, Crich SG, Belfiore S, Biancone L, Cabella C, Esposito G, Manazza AD, Aime S (2006) Magn Reson Med 55:491–497

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Di Gregorio E, Gianolio E, Stefania R, Barutello G, Digilio G, Aime S (2013) Anal Chem 85:5627–5631

    Article  PubMed  Google Scholar 

  20. 20.

    Zheng Q, Dai HQ, Merritt ME, Malloy C, Pan CY, Li WH (2005) J Am Chem Soc 127:16178–16188

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    Carney CE, MacRenaris KW, Mastarone DJ, Kasjanski DR, Hung AH, Meade TJ (2014) Bioconjugate Chem 25:945–954

    Article  CAS  Google Scholar 

  22. 22.

    Song Y, Kohlmeir EK, Meade TJ (2008) J Am Chem Soc 130;6662–6663

  23. 23.

    Pajk S, Garvas M, Strancar J, Pecar S (2011) Org Biomol Chem 9:4150–4159

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Basabe P, de Roman M, Marcos IS, Diez D, Blanco A, Bodero O, Mollinedo F, Sierra BG, Urones JG (2010) Eur J Med Chem 45:4258–4269

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    Chalker JM, Gunnoo SB, Boutureira O, Gerstberger SC, Fernandez-Gonzalez M, Bernardes GJL, Griffin L, Hailu H, Schofield CJ, Davis BG (2011) Chem Sci 2:1666–1676

    Article  CAS  Google Scholar 

  26. 26.

    Kurniasih IN, Liang H, Mohr PC, Khot G, Rabe JP, Mohr A (2015) Langmuir 31:2639–2648

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Zheng YR, Suntharalingam K, Johnstone TC, Yoo H, Lin W, Brooks JG, Lippard SJ (2014) J Am Chem Soc 136:8790–8798

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  28. 28.

    Li XS, Turanek J, Knotigova P, Kudlackova H, Masek J, Parkin S, Rankin SE, Knutson BL, Lehmler HL (2009) Colloid Surf B 73;65–74

  29. 29.

    New EJ, Congreve A, Parker D (2010) Chem Sci 1:111–118

    Article  CAS  Google Scholar 

  30. 30.

    Carney CE, Lenov IL, Baker CJ, MacRenaris KW, Eckermann AL, Sligar SG, Meade TJ (2015) Bioconjugate Chem 26:899–905

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Institutes of Health (NIH Grants R01EB005866 and P01HL108795) and by a National Science Foundation Graduate Research Fellowship (C. C.). Imaging was performed at the Northwestern University Center for Advanced Molecular Imaging generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. MRI was performed on the 7 T Bruker Pharmscan system purchased with the support of NCRR 1S10RR025624-01. Metal analysis was performed at the Northwestern University Quantitative Bioelemental Imaging Center generously supported by NASA Ames Research Center NNA06CB93G.

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Affiliations

  1. Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, and Radiology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208-3113, USA

    Christiane E. Carney, Keith W. MacRenaris & Thomas J. Meade

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  1. Christiane E. Carney
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  2. Keith W. MacRenaris
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  3. Thomas J. Meade
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Correspondence to Thomas J. Meade.

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Carney, C.E., MacRenaris, K.W. & Meade, T.J. Water-soluble lipophilic MR contrast agents for cell membrane labeling. J Biol Inorg Chem 20, 971–977 (2015). https://doi.org/10.1007/s00775-015-1280-4

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Keywords

  • MRI
  • Contrast agents
  • Gadolinium
  • Cell membrane
  • Cell labeling