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Hybrid Light Imaging Using Cerenkov Luminescence and Liquid Scintillation for Preclinical Optical Imaging In Vivo

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Abstract

Purpose

Cerenkov luminescence imaging (CLI) has recently emerged as a molecular imaging modality for radionuclides emitting β-particles. The aim of this study was to develop a hybrid light imaging (HLI) technique using a liquid scintillator to assist CLI by increasing the optical signal intensity from both β-particle and γ-ray emitting radionuclides located at deep regions in vivo.

Procedures

A commercial optical imaging system was employed to collect all images by HLI and CLI. To investigate the performance characteristics of HLI with a commercially available liquid scintillator (Emulsifier-safe), phantom experiments were conducted for two typical β-particle and γ-ray emitters, sodium iodide (Na[131I]I) and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), respectively. To evaluate the feasibility of HLI for in vivo imaging, HLI was applied to a Na[131I]I injected nu/nu mouse and an [18F]FDG injected Balb-c mouse and compared with CLI alone.

Results

Measured HLI wavelength spectra with Emulsifier-safe showed higher signal intensities than for CLI at 500–600 nm. For material preventing light transmission of 12-mm thickness, CLI imaging provided quite low intensity and obscure signals of the source. However, despite degraded spatial resolution, HLI imaging provided sustained visualization of the source shape, with signal intensities 10–14 times higher than for CLI at 10-mm thickness. Furthermore, at 0, 4, and 8-mm material thicknesses, HLI showed a strong correlation between Na[131I]I or [18F]FDG radioactivity and signal intensity, as for CLI. In vivo studies also demonstrated that HLI could successfully visualize Na[131I]I uptake in the mouse thyroid gland in the prone position and [18F]FDG accumulation in the heart in the supine position, which were not observed with CLI.

Conclusion

Our preliminary studies suggest that HLI can provide enhanced imaging of a β-particle probe emitting together with γ-rays at deep tissue locations. HLI may be a promising imaging technique to assist with preclinical in vivo imaging using CLI.

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References

  1. Robertson R, Germanos MS, Li C et al (2009) Optical imaging of Cerenkov light generation from positron-emitting radiotracers. Phys Med Biol 54:N355–N365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Spinelli AE, Marengo M, Calandrino R et al (2012) Optical imaging of radioisotopes: a novel multimodal approach to molecular imaging. Q J Nucl Med Mol Imaging 56:280–290

    CAS  PubMed  Google Scholar 

  3. Xu Y, Liu H, Cheng Z (2011) Harnessing the power of radionuclides for optical imaging: Cerenkov luminescence imaging. J Nucl Med 52:2009–2018

    Article  PubMed  Google Scholar 

  4. Cherenkov PA (1960) Radiation from high-speed particles. Science 131:136–142

    Article  CAS  PubMed  Google Scholar 

  5. Spinelli AE, Boschi F (2012) Optimizing in vivo small animal Cerenkov luminescence imaging. J Biomed Opt DOI. doi:10.1117/1.jbo.17.4.040506

    Google Scholar 

  6. Ackerman NL, Graves EE (2012) The potential for Cerenkov luminescence imaging of alpha-emitting radionuclides. Phys Med Biol DOI. doi:10.1088/0031-9155/57/3/771

    Google Scholar 

  7. Boschi F, Meo SL, Rossi PL et al (2011) Optical imaging of alpha emitters: simulations, phantom, and in vivo results. J Biomed Opt DOI. doi:10.1117/1.3663441

    Google Scholar 

  8. Liu H, Ren G, Miao Z et al (2010) Molecular optical imaging with radioactive probes. PLoS One DOI. doi:10.1371/journal.pone.0009470

    Google Scholar 

  9. Spinelli AE, D’Ambrosio D, Calderan L et al (2010) Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers. Phys Med Biol 55:483–495

    Article  PubMed  Google Scholar 

  10. Thorek D, Robertson R, Bacchus WA et al (2012) Cerenkov imaging—a new modality for molecular imaging. Am J Nucl Med Mol Imaging 2:163–173

    PubMed  PubMed Central  Google Scholar 

  11. Elrick RH, Parker RP (1968) The use of Cerenkov radiation in the measurement of beta-emitting radionuclides. Int J Appl Radiat Isot 19:263–271

    Article  CAS  PubMed  Google Scholar 

  12. Ross HH (1969) Measurement of .beta.-emitting nuclides using Cerenkov radiation. Anal Chem. doi:10.1021/ac60279a011

    Google Scholar 

  13. Spinelli AE, Kuo C, Rice BW et al (2011) Multispectral Cerenkov luminescence tomography for small animal optical imaging. Optics Express. doi:10.1364/oe.19.012605

    Google Scholar 

  14. Chin PT, Beekman CA, Buckle T et al (2012) Multispectral visualization of surgical safety-margins using fluorescent marker seeds. Am J Nucl Med Mol Imaging 2:151–162

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Lubart R, Lavie R, Friedman H (2005) The penetration of white light through human tissue. Photomed Laser Surg 23:435–436

    Article  PubMed  Google Scholar 

  16. Balkin ER, Kenoyer A, Orozco JJ et al (2014) In vivo localization of 90Y and 177Lu radioimmunoconjugates using Cerenkov luminescence imaging in a disseminated murine leukemia model. Cancer Res 74:5846–5854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Liu H, Zhang X, Xing B et al (2010) Radiation-luminescence-excited quantum dots for in vivo multiplexed optical imaging. Small 21:1087–1091

    Article  Google Scholar 

  18. Dothager RS, Goiffon RJ, Jackson E et al (2010) Cerenkov radiation energy transfer (CRET) imaging: a novel method for optical imaging of PET isotopes in biological systems. PLoS One. doi:10.1371/journal.pone.0013300

    PubMed  PubMed Central  Google Scholar 

  19. Boschi F, Spinelli AE (2012) Quantum dots excitation using pure beta minus radioisotopes emitting Cerenkov radiation. RSC Adv. doi:10.1039/C2RA22101B

    Google Scholar 

  20. Thorek DL, Ogirala A, Beattie BJ, Grimm J (2013) Quantitative imaging of disease signatures through radioactive decay signal conversion. Nat Med 19:1345–1350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Park JC, Il An G, Park SI et al (2011) Luminescence imaging using radionuclides: a potential application in molecular imaging. Nucl Med Biol 38:321–329

    Article  PubMed  Google Scholar 

  22. Carpenter CM, Ma X, Liu H et al (2014) Cerenkov luminescence endoscopy: improved molecular sensitivity with beta-emitting radiotracers. J Nucl Med 55:1905–1909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Spinelli AE, Boschi F (2015) Novel biomedical applications of Cerenkov radiation and radioluminescence imaging. Phys Med 31:120–129

    Article  PubMed  Google Scholar 

  24. Boschi F, Spinelli AE, D’Ambrosio D et al (2009) Combined optical and single photon emission imaging: preliminary results. Phys Med Biol. doi:10.1088/0031-9155/54/23/L01

    Google Scholar 

  25. Kondakov AK, Gubskiy IL, Znamenskiy IA, Chekhonin VP (2014) Possibilities of optical imaging of the 99mTc-based radiopharmaceuticals. J Biomed Opt. doi:10.1117/1.JBO.19.4.046014

    PubMed  Google Scholar 

  26. L’Annunziata M, Kessler MJ (2012) In: L’Annunziata M (ed) Handbook of radioactivity analysis, 3rd edn. Academic, San Diego, pp 438–446

    Google Scholar 

  27. Kojima A, Gotoh K, Shimamoto M et al (2015) Iodine-131 imaging using 284 keV photons with a small animal CZT-SPECT system dedicated to low-medium-energy photon detection. Ann Nucl Med. doi:10.1007/s12149-015-1028-9

    PubMed  Google Scholar 

  28. Iagaru A, Mittra E, Yaghoubi SS et al (2009) Novel strategy for a cocktail 18F-fluoride and 18F-FDG PET/CT scan for evaluation of malignancy: results of the pilot-phase study. J Nucl Med 50:501–505

    Article  PubMed  Google Scholar 

  29. Ruggiero A, Holland JP, Lewis JS, Grimm J (2010) Cerenkov luminescence imaging of medical isotopes. J Nucl Med 51:1123–1130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chin PT, Welling MM, Meskers SC et al (2013) Optical imaging as an expansion of nuclear medicine: Cerenkov-based luminescence vs fluorescence-based luminescence. Eur J Nucl Med Mol Imaging 40:1283–1291

    Article  CAS  PubMed  Google Scholar 

  31. Leo WR (1994) Techniques for nuclear and particle physics experiments: a how to approach. 2nd rev. edn. Springer-Verlag, Berlin Heidelberg, pp 157–176

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Acknowledgments

We would like to appreciate Ms. K. Kondo for her secretarial assistance and Dr. Y. Shiraishi for his technical supports.

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Authors and Affiliations

  1. Department of Radioisotope Science, Graduate School of Medical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan

    Masako Shimamoto

  2. Department of Radioisotope Science, Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan

    Kumiko Gotoh & Akihiro Kojima

  3. Department of Pathology and Experimental Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

    Koki Hasegawa

Authors
  1. Masako Shimamoto
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  2. Kumiko Gotoh
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  4. Akihiro Kojima
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Corresponding author

Correspondence to Akihiro Kojima.

Ethics declarations

All applicable institutional and/or national guidelines for the care and use of animals were followed, and all experimental procedures and protocols were approved by the Institutional Animal Care and Use Committee of Kumamoto University.

Conflict of Interest

The authors declare that they have no conflict of interest.

Funding

This study was funded in part by the Program for Leading Graduate Schools “HIGO (Health life science: Interdisciplinary and Glocal Oriented),” MEXT, Japan, and a scholarship for the Graduate School of Medical Sciences, Kumamoto University, Japan.

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Shimamoto, M., Gotoh, K., Hasegawa, K. et al. Hybrid Light Imaging Using Cerenkov Luminescence and Liquid Scintillation for Preclinical Optical Imaging In Vivo . Mol Imaging Biol 18, 500–509 (2016). https://doi.org/10.1007/s11307-016-0928-y

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  • DOI: https://doi.org/10.1007/s11307-016-0928-y

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