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In vivo near-infrared fluorescence imaging of osteoblastic activity

Nature Biotechnology volume 19, pages 1148–1154 (2001)Cite this article

Abstract

In vertebrates, the development and integrity of the skeleton requires hydroxyapatite (HA) deposition by osteoblasts. HA deposition is also a marker of, or a participant in, processes as diverse as cancer and atherosclerosis. At present, sites of osteoblastic activity can only be imaged in vivo using γ-emitting radioisotopes. The scan times required are long and the resultant radioscintigraphic images suffer from relatively low resolution. We have synthesized a near-infrared (NIR) fluorescent bisphosphonate derivative that exhibits rapid and specific binding to HA in vitro and in vivo. We demonstrate NIR light–based detection of osteoblastic activity in the living animal and discuss how this technology can be used to study skeletal development, osteoblastic metastasis, coronary atherosclerosis and other human diseases.

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Acknowledgements

We thank Daniel S. Kemp and Stephan D. Voss for helpful discussions and Alec DeGrand, Ananda Lugade, Christopher Mantzios, Kerry Petersen, Daniel Draney, Michelle Pastore, Alice Carmel, David Lee-Parritz, Angeline Warner, Stephen Moore, J. Anthony Parker, Rachel Katz-Brull, Barry Alpert, Victor Laronga, Michael Paszak, Patrick Verdier, Paul Nothnagle, Paul Millman, Kenneth Wilson, Victor Yen, Maxx Abraham and Fernando Delaville for technical assistance. We thank Rebekah Taube for proofreading and Grisel Rivera for administrative assistance. A.Z. is a Radiology Training Grant Fellow of the National Cancer Institute (NCI). A.M. and A.G.J. acknowledge support from US Public Health Service (US PHS) grant R01CA/34970. J.V.F. is supported by the Howard Hughes Medical Institute, Doris Duke Charitable Foundation (nonanimal experiments), Paul D. and Lovie S. Kemp Career Development Fund for Prostate Cancer, the Hershey Family Foundation, the Rita Leabman Memorial Fund and a grant from the NCI (R21CA88245).

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Authors and Affiliations

  1. Department of Radiology, Beth Israel Deaconess Medical Center, Boston, 02215, MA

    Atif Zaheer & Robert E. Lenkinski

  2. Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, 02115, MA

    Ashfaq Mahmood & Alun G. Jones

  3. Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, 02215, MA

    Lewis C. Cantley

  4. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, 02215, MA

    John V. Frangioni

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Zaheer, A., Lenkinski, R., Mahmood, A. et al. In vivo near-infrared fluorescence imaging of osteoblastic activity. Nat Biotechnol 19, 1148–1154 (2001). https://doi.org/10.1038/nbt1201-1148

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