Molecular Imaging and Biology

, Volume 14, Issue 2, pp 156–162

In Vivo Photoactivation Without “Light”: Use of Cherenkov Radiation to Overcome the Penetration Limit of Light

  • Chongzhao Ran
  • Zhaoda Zhang
  • Jacob Hooker
  • Anna Moore
Research Article

Abstract

Purpose

The poor tissue penetration of visible light has been a major barrier for optical imaging, photoactivatable conversions, and photodynamic therapy for in vivo targets with depths beyond 10 mm. In this report, as a proof-of-concept, we demonstrated that a positron emission tomography (PET) radiotracer, 2-deoxy-2-[18F]fluoro-d-glucose (18FDG), could be used as an alternative light source for photoactivation.

Procedures

We utilized 18FDG, which is a metabolic activity-based PET probe, as a source of light to photoactivate caged luciferin in a breast cancer animal model expressing luciferase.

Results

Bioluminescence produced from luciferin allowed for the real-time monitoring of Cherenkov radiation-promoted uncaging of the substrate.

Conclusion

The proposed method may provide a very important option for in vivo photoactivation, in particular for activation of photosensitizers for photodynamic therapy and eventually for combining radioisotope therapy and photodynamic therapy.

Key words

Cherenkov radiation Bioluminescence Photoactivation Caged luciferin 

Supplementary material

11307_2011_489_MOESM1_ESM.pdf (27 kb)
SI Fig. 1The LC–MS spectra of a water solution of DMNP-luciferin irradiated with UV 365 nm light for 5 min. Insert mass spectra of the released luciferin (left) and the unreacted DMNP-luciferin (right). (PDF 27 kb)
11307_2011_489_MOESM2_ESM.pdf (602 kb)
SI Fig. 2a Bioluminescence images of mice bearing luciferase-expressing tumors injected with luciferin. b Quantitative analysis of the images in (a). (PDF 602 kb)
11307_2011_489_MOESM3_ESM.pdf (59 kb)
SI Fig. 3Full-time course optical signal from tumor sites of control mice injected with 18FDG only. (PDF 58 kb)

References

  1. 1.
    MacCormack MA (2006) Photodynamic therapy. Adv Dermatol 22:219–258PubMedCrossRefGoogle Scholar
  2. 2.
    Celli JP, Spring BQ, Rizvi I et al (2010) Imaging and photodynamic therapy: mechanisms, monitoring, and optimization. Chem Rev 110:2795–2838PubMedCrossRefGoogle Scholar
  3. 3.
    Dolmans DE, Fukumura D, Jain RK (2003) Photodynamic therapy for cancer. Nat Rev Cancer 3:380–387PubMedCrossRefGoogle Scholar
  4. 4.
    Robertson R, Germanos MS, Li C, Mitchell GS, Cherry SR, Silva MD (2009) Optical imaging of Cerenkov light generation from positron-emitting radiotracers. Phys Med Biol 54:N355–N365PubMedCrossRefGoogle Scholar
  5. 5.
    Liu H, Ren G, Miao Z et al (2010) Molecular optical imaging with radioactive probes. PLoS One 5:e9470PubMedCrossRefGoogle Scholar
  6. 6.
    Dothager RS, Goiffon RJ, Jackson E, Harpstrite S, Piwnica-Worms D (2010) Cerenkov radiation energy transfer (CRET) imaging: a novel method for optical imaging of PET isotopes in biological systems. PLoS One 5:e13300PubMedCrossRefGoogle Scholar
  7. 7.
    Li C, Mitchell GS, Cherry SR (2010) Cerenkov luminescence tomography for small-animal imaging. Opt Lett 35:1109–1111PubMedCrossRefGoogle Scholar
  8. 8.
    Liu H, Zhang X, Xing B, Han P, Gambhir SS, Cheng Z (2010) Radiation-luminescence-excited quantum dots for in vivo multiplexed optical imaging. Small 6:1087–1091PubMedCrossRefGoogle Scholar
  9. 9.
    Ruggiero A, Holland JP, Lewis JS, Grimm J (2010) Cerenkov luminescence imaging of medical isotopes. J Nucl Med 51:1123–1130PubMedCrossRefGoogle Scholar
  10. 10.
    Spinelli AE, D’Ambrosio D, Calderan L, Marengo M, Sbarbati A, Boschi F (2010) Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers. Phys Med Biol 55:483–495PubMedCrossRefGoogle Scholar
  11. 11.
    Hu Z, Liang J, Yang W et al (2010) Experimental Cerenkov luminescence tomography of the mouse model with SPECT imaging validation. Opt Express 18:24441–24450PubMedCrossRefGoogle Scholar
  12. 12.
    Lewis MA, Kodibagkar VD, Oz OK, Mason RP (2010) On the potential for molecular imaging with Cerenkov luminescence. Opt Lett 35:3889–3891PubMedCrossRefGoogle Scholar
  13. 13.
    Mayer G, Heckel A (2006) Biologically active molecules with a “light switch”. Angew Chem Int Ed Engl 45:4900–4921PubMedCrossRefGoogle Scholar
  14. 14.
    Adams SR, Tsien RY (1993) Controlling cell chemistry with caged compounds. Annu Rev Physiol 55:755–784PubMedCrossRefGoogle Scholar
  15. 15.
    Yu H, Li J, Wu D, Qiu Z, Zhang Y (2010) Chemistry and biological applications of photo-labile organic molecules. Chem Soc Rev 39:464–473PubMedCrossRefGoogle Scholar
  16. 16.
    Lee HM, Larson DR, Lawrence DS (2009) Illuminating the chemistry of life: design, synthesis, and applications of “caged” and related photoresponsive compounds. ACS Chem Biol 4:409–427PubMedCrossRefGoogle Scholar
  17. 17.
    Fueger BJ, Czernin J, Hildebrandt I et al (2006) Impact of animal handling on the results of 18F-FDG PET studies in mice. J Nucl Med 47:999–1006PubMedGoogle Scholar
  18. 18.
    Abouzied MM, Crawford ES, Nabi HA (2005) 18F-FDG imaging: pitfalls and artifacts. J Nucl Med Technol 33:145–155PubMedGoogle Scholar
  19. 19.
    Hung JC (2002) Comparison of various requirements of the quality assurance procedures for (18)F-FDG injection. J Nucl Med 43:1495–1506PubMedGoogle Scholar
  20. 20.
    Shao Q, Jiang T, Ren G, Cheng Z, Xing B (2009) Photoactivable bioluminescent probes for imaging luciferase activity. Chem Commun (Camb) 27:4028–4030CrossRefGoogle Scholar
  21. 21.
    Yang J, Thomason DB (1993) An easily synthesized, photolyzable luciferase substrate for in vivo luciferase activity measurement. Biotechniques 15:848–850PubMedGoogle Scholar
  22. 22.
    O’Connor AE, Gallagher WM, Byrne AT (2009) Porphyrin and nonporphyrin photosensitizers in oncology: preclinical and clinical advances in photodynamic therapy. Photochem Photobiol 85:1053–1074PubMedCrossRefGoogle Scholar
  23. 23.
    Berg K, Selbo PK, Weyergang A et al (2005) Porphyrin-related photosensitizers for cancer imaging and therapeutic applications. J Microsc 218:133–147PubMedCrossRefGoogle Scholar
  24. 24.
    Kaiser PK (2007) Verteporfin photodynamic therapy and anti-angiogenic drugs: potential for combination therapy in exudative age-related macular degeneration. Curr Med Res Opin 23:477–487PubMedCrossRefGoogle Scholar
  25. 25.
    Pshenichnov I, Larionov A, Mishustin I, Greiner W (2007) PET monitoring of cancer therapy with 3He and 12 C beams: a study with the GEANT4 toolkit. Phys Med Biol 52:7295–7312PubMedCrossRefGoogle Scholar

Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2011

Authors and Affiliations

  • Chongzhao Ran
    • 1
    • 2
  • Zhaoda Zhang
    • 2
  • Jacob Hooker
    • 2
  • Anna Moore
    • 1
    • 2
  1. 1.Molecular Imaging Laboratory, Department of RadiologyMassachusetts General Hospital/Harvard Medical SchoolCharlestownUSA
  2. 2.Department of Radiology, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical ImagingMassachusetts General Hospital/Harvard Medical SchoolCharlestownUSA

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