Skip to main content
SpringerLink
Log in

Imaging of Gadolinium Spatial Distribution in Tumor Tissue by Laser Ablation Inductively Coupled Plasma Mass Spectrometry

  • Brief Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

Laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS) was utilized in postmortem imaging of gadolinium (Gd) spatial distribution in a mouse tumor model postadministration of PEGylated Gd liposomal nanoparticles.

Procedures

PEGylated liposomal nanoparticles were formulated using a paramagnetic lipid incorporating Gd, in addition to a fluorescent lipid, and injected intravenously into Balb/C nude mice bearing IGROV-1 tumors. At postinjection (2 h), the tumors and selective organs were imaged by magnetic resonance imaging (MRI) and, after excision, by histology and LA–ICP–MS.

Results

The presence of Gd within tumor tissue was confirmed by LA–ICP–MS and when correlated to histology was found to be prevalent in regions of higher vascularity. The presence of Gd in the kidneys was also confirmed.

Conclusions

We have demonstrated, in a novel manner, the use of LA–ICP–MS for the spatial detection of Gd in tumor tissue. LA–ICP–MS is valuable in providing spatio-specific information of MRI contrast agents and more importantly Gd in tumor tissue.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

LA–ICP–MS:

Laser ablation inductively coupled plasma mass spectrometry

Gd:

Gadolinium

MRI:

Magnetic resonance imaging

EPR:

Enhanced permeability and retention

HEPES:

Hydroxyethylpiperazine ethane sulfonic acid

PEG:

Polyethylene glycol

Gd.DOTA.DSA:

Gadolinium (III) 2-{4,7-bis-carboxymethyl-10-[N, N-distearylamidomethyl-N′-amido-methyl]-1,4,7,10-tetra-azacyclododec-1-yl}-acetic acid

DOPC:

1,2-Dioleoyl-sn-glycero-3-phosphocholine

DOPE:

Dioleoyl phosphatidylethanolamine

ROI:

Region of interest

Zn:

Zinc

H&E:

Hematoxylin and eosin

References

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

    Article  CAS  PubMed  Google Scholar 

  2. Torchilin VP (2007) Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J 9:E128–E147

    Article  CAS  PubMed  Google Scholar 

  3. Oliver M, Ahmad A, Kamaly N, Perouzel E, Caussin A, Keller M et al (2006) MAGfect: a novel liposome formulation for MRI labelling and visualization of cells. Org Biol Chem 4:3489–3497

    Article  CAS  Google Scholar 

  4. Kamaly N, Kalber T, Ahmad A, Oliver MH, So PW, Herlihy AH et al (2008) Bimodal paramagnetic and fluorescent liposomes for cellular and tumor magnetic resonance imaging. Bioconjug Chem 19:118–129

    Article  CAS  PubMed  Google Scholar 

  5. Gray AL (1985) Solid sample introduction by laser ablation for inductively coupled plasma source mass spectrometry. Analyst 110:551–556

    Article  CAS  Google Scholar 

  6. Becker JS, Zoriy M, Dobrowolska J, Matusch A (2007) Laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS) in elemental imaging of biological tissues and in proteomics. J Anal At Spectrom 22:736–744

    Article  CAS  Google Scholar 

  7. Becker JS, Sela H, Dobrowolska J, Zoriy M (2008) Recent applications on isotope ratio measurements by ICP–MS and LA–ICP–MS on biological samples and single particles. Int J Mass Spectrom 270:1–7

    Article  CAS  Google Scholar 

  8. Ma R, McLeod CW, Tomlinson K, Poole RK (2004) Speciation of protein-bound trace elements by gel electrophoresis and atomic spectrometry. Electrophoresis 25:2469–2477

    Article  CAS  PubMed  Google Scholar 

  9. Elliott VL, McLeod CW, Marshall PS (2005) Combination of gel electrophoresis and ICP–mass spectrometry’s—novel strategies for phosphoprotein measurement. Anal Bioanal Chem 383:416–423

    Article  CAS  PubMed  Google Scholar 

  10. Raab A, Pioselli B, Munro C, Thomas-Oates J, Feldmann J (2009) Evaluation of gel electrophoresis conditions for the separation of metal-tagged proteins with subsequent laser ablation ICP–MS detection. Electrophoresis 30:303–314

    Article  CAS  PubMed  Google Scholar 

  11. Wang S, Brown R, Gray DJ (1994) Application of laser ablation–ICP–MS to the spatially resolved micro-analysis of biological tissue. Appl Spectrosc 48:1321–1325

    Article  CAS  Google Scholar 

  12. Binet MR, Ma R, McLeod CW, Poole RK (2003) Detection and characterization of zinc- and cadmium-binding proteins in Escherichia coli by gel electrophoresis and laser ablation–inductively coupled plasma–mass spectrometry. Anal Biochem 318:30–38

    Article  CAS  PubMed  Google Scholar 

  13. Becker JS, Mounicou S, Zoriy MV, Lobinski R (2008) Analysis of metal-binding proteins separated by non-denaturating gel electrophoresis using matrix-assisted laser desorption/ionization mass spectrometry (MALDI–MS) and laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS). Talanta 76:1183–1188

    Article  CAS  PubMed  Google Scholar 

  14. Seuma J, Bunch J, Cox A, McLeod C, Bell J, Murray C (2008) Combination of immunohistochemistry and laser ablation ICP mass spectrometry for imaging of cancer biomarkers. Proteomics 8:3775–3784

    Article  CAS  PubMed  Google Scholar 

  15. Millos J, Costas-Rodriguez M, Lavilla I, Bendicho C (2008) Multielemental determination in breast cancerous and non-cancerous biopsies by inductively coupled plasma–mass spectrometry following small volume microwave-assisted digestion. Anal Chim Acta 622:77–84

    Article  CAS  PubMed  Google Scholar 

  16. Hutchinson RW, Cox AG, McLeod CW, Marshall PS, Harper A, Dawson EL et al (2005) Imaging and spatial distribution of β-amyloid peptide and metal ions in Alzheimer’s plaques by laser ablation-inductively coupled plasma–mass spectrometry. Anal Biochem 346:225–233

    Article  CAS  PubMed  Google Scholar 

  17. Dobrowolska J, Dehnhardt M, Matusch A, Zoriy M, Palomero-Gallagher N, Koscielniak P et al (2008) Quantitative imaging of zinc, copper and lead in three distinct regions of the human brain by laser ablation inductively coupled plasma mass spectrometry. Talanta 74:717–723

    Article  CAS  PubMed  Google Scholar 

  18. Becker JS, Dobrowolska J, Zoriy M, Matusch A (2008) Imaging of uranium on rat brain sections using laser ablation inductively coupled plasma mass spectrometry: a new tool for the study of critical substructures affined to heavy metals in tissues. Rapid Commun Mass SP 22:2768–2772

    Article  CAS  Google Scholar 

  19. Acquadro E, Cabella C, Ghiani S, Miragoli L, Bucci EM, Corpillo D (2009) Matrix-assisted laser desorption ionization imaging mass spectrometry detection of a magnetic resonance imaging contrast agent in mouse liver. Anal Chem 81:2779–2784

    Article  CAS  PubMed  Google Scholar 

  20. Kamaly N, Kalber TL, Thanou M, Bell JD, Miller AD (2009) Folate Receptor targeted bimodal liposomes for tumor magnetic resonance imaging. Bioconjug Chem 20:648–655

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Ms. Lorraine Lawrence for cryosectioning and histology assistance. Funding for Nazila Kamaly was provided by the MRC. The GTC wishes to thank EPSRC for funding and ImuThes Limited for recent support.

Author information

Authors and Affiliations

  1. Imaging Sciences Department, Metabolic and Molecular Imaging Group, MRC Clinical Sciences Center, Hammersmith Hospital, Imperial College London, London, W12 0NN, UK

    Nazila Kamaly, Tammy L. Kalber & Jimmy D. Bell

  2. Department of Chemistry, Imperial College Genetic Therapies Center, Imperial College London, Flowers Building, Armstrong Road, London, SW7 2AZ, UK

    Nazila Kamaly & Andrew D. Miller

  3. Department of Chemistry, Center for Analytical Sciences, University of Sheffield, Sheffield, UK

    John A. Pugh, Josephine Bunch & Cameron W. McLeod

  4. School of Chemistry, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    Josephine Bunch

Authors
  1. Nazila Kamaly
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John A. Pugh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tammy L. Kalber
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Josephine Bunch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrew D. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cameron W. McLeod
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jimmy D. Bell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cameron W. McLeod.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kamaly, N., Pugh, J.A., Kalber, T.L. et al. Imaging of Gadolinium Spatial Distribution in Tumor Tissue by Laser Ablation Inductively Coupled Plasma Mass Spectrometry. Mol Imaging Biol 12, 361–366 (2010). https://doi.org/10.1007/s11307-009-0282-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-009-0282-4

Key words

Search

Navigation