Journal
NATURE MEDICINE
Volume 18, Issue 10, Pages 1586-U197Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2935
Keywords
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Funding
- Geoffrey Beene Cancer Research Center of MSKCC
- Office of Science (BER)-US Department of Energy [DE-SC0002456]
- US National Cancer Institute [2R25-CA096945]
- US National Institutes of Health (NIH) [R24-CA83084]
- NIH Center [P30-CA08748]
- NIH Prostate SPORE [P50-CA92629]
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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 Zr-89-desferrioxamine-labeled transferrin (Zr-89-transferrin), a new positron emission tomography (PET) radiotracer that binds the transferrin receptor 1 (TFRC, CD71) with high avidity. The use of Zr-89-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, Zr-89-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 Zr-89-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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