Annotating MYC status with 89Zr-transferrin imaging

Jason P. Holland; Michael J. Evans; Samuel L. Rice; John Wongvipat; Charles L. Sawyers; Jason S. Lewis

doi:10.1038/nm.2935

Annotating MYC status with ⁸⁹Zr-transferrin imaging

Jason P. Holland, Michael J. Evans, Samuel L. Rice, John Wongvipat, Charles L. Sawyers, Jason S. Lewis

Research output: Contribution to journal › Article › peer-review

78 Scopus citations

Abstract

A noninvasive technology that quantitatively measures the activity of oncogenic signaling pathways could have a broad impact on cancer diagnosis and treatment with targeted therapies. Here we describe the development of ⁸⁹Zr-desferrioxamine-labeled transferrin (⁸⁹Zr- transferrin), a new positron emission tomography (PET) radiotracer that binds the transferrin receptor 1 (TFRC, CD71) with high avidity. The use of ⁸⁹Zr-transferrin produces high-contrast PET images that quantitatively reflect treatment-induced changes in MYC-regulated TFRC expression in a MYC-driven prostate cancer xenograft model. Moreover, ⁸⁹Zr-transferrin imaging can detect the in situ development of prostate cancer in a transgenic MYC prostate cancer model, as well as in prostatic intraepithelial neoplasia (PIN) before histological or anatomic evidence of invasive cancer. These preclinical data establish ⁸⁹Zr-transferrin as a sensitive tool for noninvasive measurement of oncogene-driven TFRC expression in prostate and potentially other cancers, with prospective near-term clinical application.

Original language	English (US)
Pages (from-to)	1586-1591
Number of pages	6
Journal	Nature medicine
Volume	18
Issue number	10
DOIs	https://doi.org/10.1038/nm.2935
State	Published - Oct 2012
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1038/nm.2935

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@article{63d63be2a7b0427a804691b83016cb6a,

title = "Annotating MYC status with 89Zr-transferrin imaging",

abstract = "A noninvasive technology that quantitatively measures the activity of oncogenic signaling pathways could have a broad impact on cancer diagnosis and treatment with targeted therapies. Here we describe the development of 89Zr-desferrioxamine-labeled transferrin (89Zr- transferrin), a new positron emission tomography (PET) radiotracer that binds the transferrin receptor 1 (TFRC, CD71) with high avidity. The use of 89Zr-transferrin produces high-contrast PET images that quantitatively reflect treatment-induced changes in MYC-regulated TFRC expression in a MYC-driven prostate cancer xenograft model. Moreover, 89Zr-transferrin imaging can detect the in situ development of prostate cancer in a transgenic MYC prostate cancer model, as well as in prostatic intraepithelial neoplasia (PIN) before histological or anatomic evidence of invasive cancer. These preclinical data establish 89Zr-transferrin as a sensitive tool for noninvasive measurement of oncogene-driven TFRC expression in prostate and potentially other cancers, with prospective near-term clinical application.",

author = "Holland, {Jason P.} and Evans, {Michael J.} and Rice, {Samuel L.} and John Wongvipat and Sawyers, {Charles L.} and Lewis, {Jason S.}",

note = "Funding Information: We thank N. Pillarsetty, B. Carver, D. Ulmert and P. Zanzonico for informative discussions, V. Longo for assistance with the in vivo studies, and M. Balbas for help with in vitro experiments. We thank C. Le and D. Winkleman for recording the MRI data and B. Beattie for assistance with co-registering PET/CT data. We thank M. McDevitt for assistance with HPLC stability studies. We also thank the staff of the Radiochemistry and Cyclotron Core at MSKCC. Funded in part by the Geoffrey Beene Cancer Research Center of MSKCC (J.S.L.), the Office of Science (BER)–US Department of Energy (Award DE-SC0002456, J.S.L.) and the R25T Molecular Imaging for Training in Oncology Program (2R25-CA096945; principal investigator H. Hricak; fellows: M.J.E. and S.L.R.) from the US National Cancer Institute. Technical services provided by the MSKCC Small-Animal Imaging Core Facility were supported in part by the US National Institutes of Health (NIH) grant R24-CA83084; NIH Center grant P30-CA08748; and NIH Prostate SPORE, P50-CA92629.",

year = "2012",

month = oct,

doi = "10.1038/nm.2935",

language = "English (US)",

volume = "18",

pages = "1586--1591",

journal = "Nature medicine",

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T1 - Annotating MYC status with 89Zr-transferrin imaging

AU - Holland, Jason P.

AU - Evans, Michael J.

AU - Rice, Samuel L.

AU - Wongvipat, John

AU - Sawyers, Charles L.

AU - Lewis, Jason S.

N1 - Funding Information: We thank N. Pillarsetty, B. Carver, D. Ulmert and P. Zanzonico for informative discussions, V. Longo for assistance with the in vivo studies, and M. Balbas for help with in vitro experiments. We thank C. Le and D. Winkleman for recording the MRI data and B. Beattie for assistance with co-registering PET/CT data. We thank M. McDevitt for assistance with HPLC stability studies. We also thank the staff of the Radiochemistry and Cyclotron Core at MSKCC. Funded in part by the Geoffrey Beene Cancer Research Center of MSKCC (J.S.L.), the Office of Science (BER)–US Department of Energy (Award DE-SC0002456, J.S.L.) and the R25T Molecular Imaging for Training in Oncology Program (2R25-CA096945; principal investigator H. Hricak; fellows: M.J.E. and S.L.R.) from the US National Cancer Institute. Technical services provided by the MSKCC Small-Animal Imaging Core Facility were supported in part by the US National Institutes of Health (NIH) grant R24-CA83084; NIH Center grant P30-CA08748; and NIH Prostate SPORE, P50-CA92629.

PY - 2012/10

Y1 - 2012/10

N2 - A noninvasive technology that quantitatively measures the activity of oncogenic signaling pathways could have a broad impact on cancer diagnosis and treatment with targeted therapies. Here we describe the development of 89Zr-desferrioxamine-labeled transferrin (89Zr- transferrin), a new positron emission tomography (PET) radiotracer that binds the transferrin receptor 1 (TFRC, CD71) with high avidity. The use of 89Zr-transferrin produces high-contrast PET images that quantitatively reflect treatment-induced changes in MYC-regulated TFRC expression in a MYC-driven prostate cancer xenograft model. Moreover, 89Zr-transferrin imaging can detect the in situ development of prostate cancer in a transgenic MYC prostate cancer model, as well as in prostatic intraepithelial neoplasia (PIN) before histological or anatomic evidence of invasive cancer. These preclinical data establish 89Zr-transferrin as a sensitive tool for noninvasive measurement of oncogene-driven TFRC expression in prostate and potentially other cancers, with prospective near-term clinical application.

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Annotating MYC status with ⁸⁹Zr-transferrin imaging

Abstract

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