Annotating MYC status with 89Zr-transferrin imaging

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.