Skip to main content

Advertisement

SpringerLink
Log in

Smart optical probes for near-infrared fluorescence imaging of Alzheimer’s disease pathology

  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

An Erratum to this article was published on 20 March 2008

Abstract

Purpose

Near-infrared fluorescent probes for amyloid-beta (Aβ) are an exciting option for molecular imaging in Alzheimer’s disease research and may translate to clinical diagnostics. However, Aβ-targeted optical probes often suffer from poor specificity and slow clearance from the brain. We are designing smart optical probes that emit characteristic fluorescence signal only when bound to Aβ.

Methods

We synthesized a family of dyes and tested Aβ-binding sensitivity with fluorescence spectroscopy and tissue-staining.

Results

Select compounds exhibited Aβ-dependent changes in fluorescence quantum yield, lifetime, and emission spectra that may be imaged microscopically or in vivo using new lifetime and spectral fluorescence imaging techniques.

Conclusion

Smart optical probes that turn on when bound to Aβ will improve amyloid detection and may enable quantitative molecular imaging in vivo.

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.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Hyman BT, Trojanowski JQ. Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol. 1997;56(10):1095–7.

    Article  PubMed  CAS  Google Scholar 

  2. Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature. 1995;373(6514):523–7.

    Article  PubMed  CAS  Google Scholar 

  3. Hsiao KK, Borchelt DR, Olson K, Johannsdottir R, Kitt C, Yunis W, et al. Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins. Neuron. 1995;15(5):1203–18.

    Article  PubMed  CAS  Google Scholar 

  4. Spires TL, Hyman BT. Neuronal structure is altered by amyloid plaques. Rev Neurosci. 2004;15(4):267–78.

    PubMed  Google Scholar 

  5. Poduslo JF, Wengenack TM, Curran GL, Wisniewski T, Sigurdsson EM, Macura SI, et al. Molecular targeting of Alzheimer’s amyloid plaques for contrast-enhanced magnetic resonance imaging. Neurobiol Dis. 2002;11(2):315–29.

    Article  PubMed  CAS  Google Scholar 

  6. Higuchi M, Iwata N, Matsuba Y, Sato K, Sasamoto K, Saido TC. 19F and 1H MRI detection of amyloid beta plaques in vivo. Nat Neurosci. 2005;8(4):527–33.

    Article  PubMed  CAS  Google Scholar 

  7. Shoghi-Jadid K, Small GW, Agdeppa ED, Kepe V, Ercoli LM, Siddarth P, et al. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry. 2002;10(1):24–35.

    PubMed  Google Scholar 

  8. Ono M, Wilson A, Nobrega J, Westaway D, Verhoeff P, Zhuang ZP, et al. 11C-labeled stilbene derivatives as Abeta-aggregate-specific PET imaging agents for Alzheimer's disease. Nucl Med Biol. 2003;30(6):565–71.

    Article  PubMed  CAS  Google Scholar 

  9. Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol. 2004;55(3):306–19.

    Article  PubMed  CAS  Google Scholar 

  10. Engler H, Forsberg A, Almkvist O, Blomquist G, Larsson E, Savitcheva I, et al. Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain. 2006;129(11):2856–66.

    Article  PubMed  Google Scholar 

  11. Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, et al. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007;68(20):1718–25.

    Article  PubMed  CAS  Google Scholar 

  12. Hintersteiner M, Enz A, Frey P, Jaton AL, Kinzy W, Kneuer R, et al. In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe. Nat Biotechnol. 2005;23(5):577–83.

    Article  PubMed  CAS  Google Scholar 

  13. Nesterov EE, Skoch J, Hyman BT, Klunk WE, Bacskai BJ, Swager TM. In vivo optical imaging of amyloid aggregates in brain: design of fluorescent markers. Angew Chem Int Ed Engl. 2005;44(34):5452–6.

    Article  PubMed  CAS  Google Scholar 

  14. Godavarty A, Sevick-Muraca EM, Eppstein MJ. Three-dimensional fluorescence lifetime tomography. Med Phys. 2005;32(4):992–1000.

    Article  PubMed  Google Scholar 

  15. Kumar AT, Skoch J, Bacskai BJ, Boas DA, Dunn AK. Fluorescence-lifetime-based tomography for turbid media. Opt Lett. 2005;30(24):3347–9.

    Article  PubMed  Google Scholar 

  16. Zavattini G, Vecchi S, Mitchell G, Weisser U, Leahy RM, Pichler BJ, et al. A hyperspectral fluorescence system for 3D in vivo optical imaging. Phys Med Biol. 2006;51(8):2029–43.

    Article  PubMed  CAS  Google Scholar 

  17. Dunphy I, Vinogradov SA, Wilson DF. Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence. Anal Biochem. 2002;310(2):191–8.

    Article  PubMed  CAS  Google Scholar 

  18. Wilms CD, Eilers J. Photo-physical properties of Ca2+indicator dyes suitable for two-photon fluorescence-lifetime recordings. J Microsc. 2007;225(Pt 3):209–13.

    Article  PubMed  CAS  Google Scholar 

  19. Berezin MY, Lee H, Akers W, Achilefu S. Near infrared dyes as lifetime solvatochromic probes for micropolarity measurements of biological systems. Biophys J. 2007;93(8):2892–9.

    Article  PubMed  CAS  Google Scholar 

  20. Venkatraman P, Nguyen TT, Sainlos M, Bilsel O, Chitta S, Imperiali B, et al. Fluorogenic probes for monitoring peptide binding to class II MHC proteins in living cells. Nat Chem Biol. 2007;3(4):222–8.

    Article  PubMed  CAS  Google Scholar 

  21. Olmsted J III. Calorimetric determination of absolute fluorescence quantum yields. J Phys Chem. 1979;83(20):2581–4.

    Article  CAS  Google Scholar 

  22. LeVine H 3rd. Thioflavine T interaction with synthetic Alzheimer’s disease beta-amyloid peptides: detection of amyloid aggregation in solution. Protein Sci. 1993;2(3):404–10.

    Article  PubMed  CAS  Google Scholar 

  23. Voropai ES, Samtsov MP, Kaplevskii KN, Maskevich AA, Stepuro VI, Povarova OI, et al. Spectral properties of Thioflavin T and its complexes with amyloid fibrils. J Appl Spectrosc. 2003;70(6):868–74.

    Article  CAS  Google Scholar 

  24. Kumar ATN, Raymond SB, Boverman G, Boas DA, Bacskai BJ. Time resolved fluorescence tomography based on lifetime contrast. Opt Express. 2006;14:12255.

    Article  PubMed  Google Scholar 

  25. Levenson RM, Mansfield JR. Multispectral imaging in biology and medicine: slices of life. Cytometry A. 2006;69(8):748–58.

    PubMed  Google Scholar 

  26. Tam JM, Upadhyay R, Pittet MJ, Weissleder R, Mahmood U. Improved in vivo whole-animal detection limits of green fluorescent protein-expressing tumor lines by spectral fluorescence imaging. Mol Imaging. 2007;6(4):269–76.

    PubMed  CAS  Google Scholar 

  27. Mathis CA, Wang Y, Klunk WE. Imaging beta-amyloid plaques and neurofibrillary tangles in the aging human brain. Curr Pharm Des. 2004;10(13):1469–92.

    Article  PubMed  CAS  Google Scholar 

  28. Wang Y, Mathis CA, Huang GF, Debnath ML, Holt DP, Shao L, Klunk WE. Effects of lipophilicity on the affinity and nonspecific binding of iodinated benzothiazole derivatives. J Mol Neurosci. 2003;20(3):255–60.

    Article  PubMed  Google Scholar 

  29. Groenning M, Norrman M, Flink JM, van de Weert M, Bukrinsky JT, Schluckebier G, et al. Binding mode of Thioflavin T in insulin amyloid fibrils. J Struct Biol. 2007;159(3):483–97.

    Article  PubMed  CAS  Google Scholar 

  30. Groenning M, Olsen L, van de Weert M, Flink JM, Frokjaer S, Jargensen FS. Study on the binding of Thioflavin T to beta-sheet-rich and non-beta-sheet cavities. J Struct Biol. 2007;158(3):358–69.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by NIH EB00768 and AG026240 (BJB) and the US Army through the Institute for Soldier Nanotechnologies, DAAD-19-02-D-0002 (TMS). S. B. Raymond was supported with the NDSEG fellowship, the Harvard University Ashford fellowship, and T32 EB001680.

Conflict of interest statement

The authors declare that they have no relevant financial or any other interests in this manuscript.

Author information

Authors and Affiliations

  1. Alzheimer’s Disease Research Unit, Department of Neurology, Massachusetts General Hospital, 114 16th St, Charlestown, MA, 02129, USA

    Scott B. Raymond & Brian J. Bacskai

  2. Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, Denver, CO, 80262, USA

    Jesse Skoch

  3. Department of Chemistry, Louisiana State University, Baton Rouge, LA, 70803, USA

    Evgueni E. Nesterov

  4. Department of Chemistry and Institute for Soldier Nanotechnologies, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Ivory D. Hills & Timothy M. Swager

Authors
  1. Scott B. Raymond
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jesse Skoch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ivory D. Hills
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Evgueni E. Nesterov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Timothy M. Swager
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Brian J. Bacskai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brian J. Bacskai.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00259-008-0749-6

An erratum to this article is available at http://dx.doi.org/10.1007/s00259-008-0749-6.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Raymond, S.B., Skoch, J., Hills, I.D. et al. Smart optical probes for near-infrared fluorescence imaging of Alzheimer’s disease pathology. Eur J Nucl Med Mol Imaging 35 (Suppl 1), 93–98 (2008). https://doi.org/10.1007/s00259-007-0708-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-007-0708-7

Keywords

Search

Navigation