Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Simultaneous visualization of multiple radionuclides in vivo

Abstract

The insufficient energy and spatial resolutions of radionuclide imaging with conventional scintillation detectors restrict the visualization of multiple radionuclides and of microstructures in tissue. Here we report the development and performance of an imaging system equipped with a cadmium telluride diode detector that achieves an energy resolution of 1.7% at 140 keV and a spatial resolution of 250 μm. The combination of high-resolution spectra fitted to an X-ray analysis model of the emission lines of the radionuclides in a chosen energy band allowed us to accurately determine individual radiation activities from three radionuclides to simultaneously visualize thyroid tissue (via intravenously administered iodine-125), mandibular lymph nodes (via the intramuscular injection of indium-111) and parotid lymph nodes (via a subcutaneous injection of technetium-99m) in mice. Multi-radionuclide imaging may find advantageous applications in biomedical imaging.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Separation of the spectral components from overlapping nuclides.
Fig. 2: Quantification of radioactivity.
Fig. 3: Evaluation of spatial resolutions.
Fig. 4: Multi-radionuclide in vivo imaging.

Similar content being viewed by others

Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. The raw and analysed datasets generated during the study are too large to be publicly shared, yet they are available for research purposes from the corresponding authors on reasonable request. Source data are provided with this paper.

Code availability

The custom code for data collection, spectral fitting and image reconstruction is intended to be used for the joint development of radionuclide imaging systems with companies. The code is, however, available for research purposes from the corresponding authors on request.

References

  1. Jang, B. S. MicroSPECT and MicroPET imaging of small animals for drug development. Toxicol. Res 29, 1–6 (2013).

    Article  CAS  Google Scholar 

  2. Weissleder, R. & Pittet, M. J. Imaging in the era of molecular oncology. Nature 452, 580–589 (2008).

    Article  CAS  Google Scholar 

  3. Blow, N. In vivo molecular imaging: the inside job. Nat. Methods 6, 465–469 (2009).

    Article  CAS  Google Scholar 

  4. Franc, B. L., Acton, P. D., Mari, C. & Hasegawa, B. H. Small-animal SPECT and SPECT/CT: important tools for preclinical investigation. J. Nucl. Med. 49, 1651–1663 (2008).

    Article  Google Scholar 

  5. Nishimura, T. et al. Prediction of functional recovery and prognosis in patients with acute myocardial infarction by 123I-BMIPP and 201Tl myocardial single photon emission computed tomography: a multicenter trial. Ann. Nucl. Med 12, 237–248 (1998).

    Article  CAS  Google Scholar 

  6. Yamanaka, H., Suzuki, T., Kishida, H., Nagasawa, K. & Takano, T. Relationship between the mismatch of 123I-BMIPP and 201Tl myocardial single-photon emission computed tomography and autonomic nervous system activity in patients with acute myocardial infarction. Int. Heart J. 47, 193–207 (2006).

    Article  CAS  Google Scholar 

  7. Kawaguchi, K. et al. Quantitative estimation of infarct size by simultaneous dual radionuclide single photon emission computed tomography: comparison with peak serum creatine kinase activity. Am. Heart J. 121, 1353–1360 (1991).

    Article  CAS  Google Scholar 

  8. Hashimoto, T. et al. Significance of technetium-99m/thallium-201 overlap on simultaneous dual emission computed tomography in acute myocardial infarction. Am. J. Cardiol. 61, 1181–1186 (1988).

    Article  CAS  Google Scholar 

  9. Mullan, B. P. Nuclear medicine imaging of the parathyroid. Otolaryngol. Clin. North Am. 37, 909–939 (2004).

    Article  Google Scholar 

  10. Lukas, M., Kluge, A., Beindorff, N. & Brenner, W. Multi-isotope capabilities of a small-animal multi-pinhole SPECT system. J. Nucl. Med. 61, 152–161 (2020).

    Article  CAS  Google Scholar 

  11. Takeda, S. et al. A high-resolution CdTe imaging detector with multi-pinhole optics for in-vivo molecular imaging. Nucl. Instrum. Methods A 912, 57–60 (2018).

    Article  CAS  Google Scholar 

  12. Takahashi, T. et al. High-resolution Schottky CdTe diode for hard X-ray and gamma-ray astronomy. Nucl. Instrum. Methods A 436, 111–119 (1999).

    Article  CAS  Google Scholar 

  13. Takahashi, T. & Watanabe, S. Recent progress in CdTe and CdZnTe detectors. IEEE Trans. Nucl. Sci. 48, 950–959 (2001).

    Article  CAS  Google Scholar 

  14. Katsuragawa, M. et al. Suzaku X-ray observations of the mixed-morphology supernova remnant CTB 1. Publ. Astron. Soc. Jpn 70, 110 (2018).

    Article  CAS  Google Scholar 

  15. Matsumura, H., Tanaka, T., Uchida, H., Okon, H. & Tsuru, T. G. Toward the understanding of the physical origin of recombining plasma in the supernova remnant IC 443. Astrophys. J. 851, 73 (2017).

    Article  Google Scholar 

  16. Kobayashi, H. et al. Multimodal nanoprobes for radionuclide and five-color near-infrared optical lymphatic imaging. ACS Nano 1, 258–264 (2007).

    Article  CAS  Google Scholar 

  17. Tavares, M. G. et al. The use of 99m Tc-phytate for sentinel node mapping in melanoma, breast cancer and vulvar cancer: a study of 100 cases. Eur. J. Nucl. Med. 28, 1597–1604 (2001).

    Article  CAS  Google Scholar 

  18. Riedel, C., Dohan, O., De la Vieja, A., Ginter, C. S. & Carrasco, N. Journey of the iodide transporter NIS: from its molecular identification to its clinical role in cancer. Trends Biochem. Sci. 26, 490–496 (2001).

    Article  CAS  Google Scholar 

  19. Dadachova, E. & Carrasco, N. The Na/I symporter (NIS): imaging and therapeutic applications. Semin. Nucl. Med. 34, 23–31 (2004).

    Article  Google Scholar 

  20. Ito, T. et al. Experimental evaluation of the GE NM/CT 870 CZT clinical SPECT system equipped with WEHR and MEHRS collimator. J. Appl. Clin. Med Phys. 22, 165–177 (2021).

    Article  Google Scholar 

  21. Erlandsson, K., Kacperski, K., van Gramberg, D. & Hutton, B. F. Performance evaluation of D-SPECT: a novel SPECT system for nuclear cardiology. Phys. Med. Biol. 54, 2635–2649 (2009).

    Article  Google Scholar 

  22. Matsunari, I. et al. Performance evaluation of the eXplore speCZT preclinical imaging system. Ann. Nucl. Med 28, 484–497 (2014).

    Article  CAS  Google Scholar 

  23. Weng, F., Zan, Y., Bagchi, S., Huang, Q. & Seo, Y. Energy window optimization in dual-isotope SPECT brain imaging with 99mTc/123I via CZT-based detectors. J. Nucl. Med. 56, 1803–1803 (2015).

    Google Scholar 

  24. Laforest, R. et al. Dual nuclide quantitative imaging with 99mTc/123I using CZT gamma camera. J. Nucl. Med. 58, 742–742 (2017).

    Google Scholar 

  25. Ivashchenko, O. et al. Quarter-millimeter-resolution molecular mouse imaging with U-SPECT+. Mol. Imaging https://doi.org/10.2310/7290.2014.00053 (2015).

  26. Lifante, J., Shen, Y., Ximendes, E., Rodríguez, E. M. & Ortgies, D. H. The role of tissue fluorescence in in vivo optical bioimaging. J. Appl. Phys. 128, 171101 (2020).

    Article  CAS  Google Scholar 

  27. Watanabe, S. et al. High energy resolution hard X-ray and gamma-ray imagers using CdTe diode devices. IEEE Trans. Nucl. Sci. 56, 777–782 (2009).

    Article  CAS  Google Scholar 

  28. Takahashi, T. et al. Hitomi (ASTRO-H) X-ray astronomy satellite. J. Astron. TeIesc. Instrum. Syst. 4, 021402 (2018).

    Google Scholar 

  29. Nakazawa, K. et al. Hard X-ray imager onboard Hitomi (ASTRO-H). J. Astron. Telesc. Instrum. Syst. 4, 021410 (2018).

    Article  Google Scholar 

  30. Sato, G. et al. The Si/CdTe semiconductor camera of the ASTRO-H Hard X-ray Imager (HXI). Nucl. Instrum. Methods Phys. Res. A 831, 235–241 (2016).

    Article  CAS  Google Scholar 

  31. Update of X Ray and Gamma Ray Decay Data Standards for Detector Calibration and Other Applications (International Atomic Energy Agency, 2007).

  32. Lange, K. & Carson, R. EM reconstruction algorithms for emission and transmission tomography. J. Comput. Assist. Tomogr. 8, 306–316 (1984).

    CAS  PubMed  Google Scholar 

  33. Brun, R. & Rademakers, F. ROOT—an object oriented data analysis framework. Nucl. Instrum. Methods Phys. Res. A 389, 81–86 (1997).

    Article  CAS  Google Scholar 

  34. Robitaille, T. P. et al. Astropy: a community Python package for astronomy. Astron. Astrophys. 558, A33 (2013).

    Article  Google Scholar 

  35. Price-Whelan, A. M. et al. The Astropy project: building an open-science project and status of the v2. 0 core package. Astron. J. 156, 123 (2018).

    Article  Google Scholar 

Download references

Acknowledgements

This research was supported by World Premier International Research Center Initiative (WPI) (A.Y., S.T., T.O. and T.T.), MEXT, JAPAN, a matching fund programme of Centers for Inter-University Collaboration from ISAS/JAXA (A.Y, S.T. and T.O.) and MEXT JSPS KAKENHI grant numbers 18H02700 (S.T. and A.Y.), 18H05463 (T.T., A.Y., S.T., T.O. and M.K.) and 20K16692 (A.Y.).

Author information

Authors and Affiliations

Authors

Contributions

A.Y. initiated the project. A.Y. designed the experiments with help from H. Mizuma, Y.K. and H.F. A.Y., S.T., T.O., G.Y. and T.K. performed the experiments with help from I.O.U. and K.O., and H.F., S.T., M.K., G.Y. and H. Matsumura analysed the data. S.W., S.T., T.T. and A.Y. contributed materials/analysis tools. A.Y. wrote the paper with help from P.C., T.T., H.F., H. Mizuma and Y.K.

Corresponding authors

Correspondence to Atsushi Yagishita or Shin’ichiro Takeda.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Biomedical Engineering thanks Ramsey Badawi, Paul Lecoq and Marco Pizzichemi for their contribution to the peer review of this work. Peer reviewer reports are available.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Source data

Source Data Fig. 2

Source data.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yagishita, A., Takeda, S., Katsuragawa, M. et al. Simultaneous visualization of multiple radionuclides in vivo. Nat. Biomed. Eng 6, 640–647 (2022). https://doi.org/10.1038/s41551-022-00866-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41551-022-00866-6

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing