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Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging

Nature Medicine volume 21, pages 192–197 (2015)Cite this article

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Abstract

The typical method for creating targeted contrast agents requires covalent conjugation of separate targeting and fluorophore domains. In this study, we demonstrate that it is possible to create near-infrared (NIR) fluorophores with different tissue specificities driven by their inherent chemical structures. Thus, a single compact molecule performs both targeting and imaging. We use this strategy to solve a major problem in head and neck surgery: the identification and preservation of parathyroid and thyroid glands. We synthesized 700-nm and 800-nm halogenated fluorophores that show high uptake into these glands after a single intravenous (IV) injection of 0.06 mg kg−1 in a pig. By using a dual-channel NIR imaging system, we observed—in real time and with high sensitivity—the unambiguous distinction of parathyroid and thyroid glands simultaneously in the context of blood and surrounding soft tissue. This novel technology lays a foundation for performing head and neck surgery with increased precision and efficiency along with potentially lower morbidity, and it provides a general strategy for developing targeted NIR fluorophores.

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Figure 1
Figure 2: Thyroid targeting efficiency in mice.
Figure 3: In vivo parathyroid and thyroid imaging using T700-F and T800-F in pigs.
Figure 4: Simultaneous in vivo NIR imaging of parathyroid and thyroid glands in rats.
Figure 5: Simultaneous in vivo NIR imaging of parathyroid and thyroid glands in pigs.

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Acknowledgements

We thank D. Burrington, Jr. for editing and E. Trabucchi for administrative assistance. This study was supported by the following grants from the National Institutes of Health: NCI BRP grant no. R01-CA-115296 (J.V.F.), NIBIB grant nos. R01-EB-010022 (J.V.F.) and R01-EB-011523 (H.S.C.), and a grant from the Dana Foundation in brain and immuno-imaging (H.S.C.). The contents of this paper are solely the responsibility of the authors and do not necessarily reflect the official views of the National Institutes of Health

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Author notes

  1. Hoon Hyun and Min Ho Park: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA

    Hoon Hyun, Min Ho Park, Hideyuki Wada, John V Frangioni & Hak Soo Choi

  2. Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA

    John V Frangioni

  3. Department of Surgery, Chonnam National University Medical School, Gwangju, South Korea

    Min Ho Park

  4. Department of Chemistry, Georgia State University, Atlanta, Georgia, USA

    Eric A Owens & Maged Henary

  5. Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA

    Eric A Owens & Maged Henary

  6. Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands

    Henricus J M Handgraaf & Alexander L Vahrmeijer

  7. Curadel, LLC, Worcester, Massachusetts, USA

    John V Frangioni

  8. Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, South Korea

    Hak Soo Choi

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  1. Hoon Hyun
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Contributions

H.H., M.H.P., H.W., E.A.O. and H.J.M.H. performed the experiments. H.H., M.H.P., M.H., A.L.V., J.V.F. and H.S.C. reviewed, analyzed and interpreted the data. H.H., J.V.F. and H.S.C. wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Hak Soo Choi.

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Competing interests

J.V.F. is currently CEO of Curadel, LLC, which has licensed FLARE imaging systems and contrast agents from the Beth Israel Deaconess Medical Center.

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Supplementary Methods and Supplementary Figures 1–5 (PDF 1603 kb)

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Hyun, H., Park, M., Owens, E. et al. Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging. Nat Med 21, 192–197 (2015). https://doi.org/10.1038/nm.3728

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